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Trial record 84 of 163 for:    ISOTRETINOIN

Combination Chemotherapy and Surgery With or Without Isotretinoin in Treating Young Patients With Neuroblastoma

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ClinicalTrials.gov Identifier: NCT00499616
Recruitment Status : Completed
First Posted : July 11, 2007
Results First Posted : June 27, 2017
Last Update Posted : June 21, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neuroblastoma
Interventions Drug: carboplatin
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: topotecan hydrochloride
Drug: Isotretinoin
Procedure: Surgery
Drug: Filgrastim
Enrollment 464
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Group 2 (Chemotherapy, Surgery) Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy) Non-intermediate Risk Enrolled on Intermediate Risk Trial
Hide Arm/Group Description 2 courses of initial chemotherapy (6 wks) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Partial response (PR) to chemo go to observation. No PR: 2-6 additional courses of chemo (beginning course 3 - cyclophosphamide, etoposide, filgrastim, carboplatin, doxorubicin hydrochloride). No PR after additional chemotherapy proceed to retrieval chemo: cyclophosphamide and topotecan hydrochloride on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may also undergo surgery. 4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery. 8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients < 12 months of age with stg 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemo proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.

The no treatment group assignment patients may have received some treatment on ANBL0531 but they were not evaluable on this study due to being non-intermediate risk and hence did not receive a treatment assignment on ANBL0531.

Surgery: With the exception of patients with INSS 4S disease, patients undergo surgery to remove as much of the primary tumor and involved lymph nodes as can safely be accomplished.

Period Title: Overall Study
Started 176 142 89 57
Completed 161 114 53 0
Not Completed 15 28 36 57
Reason Not Completed
Death             1             5             3             1
Lack of Efficacy             5             0             19             0
Lost to Follow-up             0             0             1             0
Physician Decision             6             16             9             0
Withdrawal by Subject             1             0             1             0
Ineligible             1             2             0             15
Not evaluable             0             0             0             41
Patient/Parent Refusal             1             5             3             0
Arm/Group Title Group 2 (Chemotherapy, Surgery) Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy) Non-intermediate Risk Enrolled on Intermediate Risk Trial Total
Hide Arm/Group Description 2 courses of initial chemotherapy (6 wks) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Partial response (PR) to chemo go to observation. No PR: 2-6 additional courses of chemo (beginning course 3 - cyclophosphamide, etoposide, filgrastim, carboplatin, doxorubicin hydrochloride). No PR after additional chemotherapy proceed to retrieval chemo: cyclophosphamide and topotecan hydrochloride on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may also undergo surgery. 4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery. 8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients < 12 months of age with stg 3, 4, or 4S disease who achieve a very good PR (VGPR) to chemo (with the exception of resolution of skin or liver metastases in stage 4S patients) proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.

The no treatment group assignment patients may have received some treatment on ANBL0531 but they were not evaluable on this study due to being non-intermediate risk and hence did not receive a treatment assignment on ANBL0531.

Surgery: With the exception of patients with INSS 4S disease, patients undergo surgery to remove as much of the primary tumor and involved lymph nodes as can safely be accomplished.

Total of all reporting groups
Overall Number of Baseline Participants 176 142 89 57 464
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 176 participants 142 participants 89 participants 57 participants 464 participants
<=18 years
176
 100.0%
142
 100.0%
89
 100.0%
57
 100.0%
464
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 176 participants 142 participants 89 participants 57 participants 464 participants
1.23  (1.47) .74  (.89) .60  (.36) 1.51  (1.83) 0.99  (1.26)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 176 participants 142 participants 89 participants 57 participants 464 participants
Female
70
  39.8%
72
  50.7%
49
  55.1%
26
  45.6%
217
  46.8%
Male
106
  60.2%
70
  49.3%
40
  44.9%
31
  54.4%
247
  53.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 176 participants 142 participants 89 participants 57 participants 464 participants
Hispanic or Latino
18
  10.2%
26
  18.3%
7
   7.9%
6
  10.5%
57
  12.3%
Not Hispanic or Latino
150
  85.2%
109
  76.8%
74
  83.1%
49
  86.0%
382
  82.3%
Unknown or Not Reported
8
   4.5%
7
   4.9%
8
   9.0%
2
   3.5%
25
   5.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 176 participants 142 participants 89 participants 57 participants 464 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
2
   2.2%
0
   0.0%
2
   0.4%
Asian
5
   2.8%
8
   5.6%
4
   4.5%
2
   3.5%
19
   4.1%
Native Hawaiian or Other Pacific Islander
3
   1.7%
4
   2.8%
0
   0.0%
1
   1.8%
8
   1.7%
Black or African American
23
  13.1%
12
   8.5%
8
   9.0%
9
  15.8%
52
  11.2%
White
133
  75.6%
92
  64.8%
59
  66.3%
40
  70.2%
324
  69.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
12
   6.8%
26
  18.3%
16
  18.0%
5
   8.8%
59
  12.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 176 participants 142 participants 89 participants 57 participants 464 participants
New Zealand 2 0 1 0 3
Canada 16 6 10 5 37
United States 153 131 78 50 412
Australia 5 5 0 2 12
1.Primary Outcome
Title Overall Survival (OS) Rates
Hide Description OS time is calculated from date of enrollment until death, or until last contact if the patient is alive.
Time Frame 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible intermediate risk patients.
Arm/Group Title Group 2 (Chemotherapy, Surgery) Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)
Hide Arm/Group Description:
2 courses of initial chemotherapy (6 wks) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Partial response (PR) to chemo go to observation. No PR: 2-6 additional courses of chemo (beginning course 3 - cyclophosphamide, etoposide, filgrastim, carboplatin, doxorubicin hydrochloride). No PR after additional chemotherapy proceed to retrieval chemo: cyclophosphamide and topotecan hydrochloride on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may also undergo surgery.
4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients < 12 months of age with stg 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemo proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
Overall Number of Participants Analyzed 175 140 89
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
99.4
(98.3 to 100.0)
93.5
(89.4 to 97.7)
88.4
(81.5 to 95.3)
2.Primary Outcome
Title Definitive Determination of the Prognostic Ability of 1p and 11q
Hide Description Addressed by a descriptive comparison of the EFS and OS rates for patients with 1p loss vs without 1p loss, and for those with unbalanced 11q vs normal 11q.
Time Frame At baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible intermediate risk patients with 1p and 11q data.
Arm/Group Title Group 2 (Chemotherapy, Surgery) Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)
Hide Arm/Group Description:
2 courses of initial chemotherapy (6 wks) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Partial response (PR) to chemo go to observation. No PR: 2-6 additional courses of chemo (beginning course 3 - cyclophosphamide, etoposide, filgrastim, carboplatin, doxorubicin hydrochloride). No PR after additional chemotherapy proceed to retrieval chemo: cyclophosphamide and topotecan hydrochloride on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may also undergo surgery.
4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients < 12 months of age with stg 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemo proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
Overall Number of Participants Analyzed 175 104 62
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of 3 yr EFS/OS rate
EFS Eligible & evaluable patients without 1p loss Number Analyzed 175 participants 85 participants 40 participants
87.2
(82.0 to 92.4)
84.6
(76.8 to 92.5)
65.4
(50.0 to 80.8)
OS Eligible & evaluable patients without 1p loss Number Analyzed 175 participants 85 participants 40 participants
99.4
(98.3 to 100.0)
92.8
(87.2 to 98.4)
83.7
(71.6 to 95.8)
EFS Eligible & evaluable patients with 1p loss Number Analyzed 0 participants 19 participants 22 participants
94.7
(84.7 to 100.0)
81.8
(65.2 to 98.4)
OS Eligible & evaluable patients with 1p loss Number Analyzed 0 participants 19 participants 22 participants
94.7
(84.7 to 100.0)
95.5
(86.5 to 100.0)
EFS Eligible & evaluable patients with normal 11q Number Analyzed 175 participants 96 participants 43 participants
87.2
(82.0 to 92.4)
87.5
(80.7 to 94.2)
73.3
(59.5 to 87.0)
OS Eligible & evaluable patients with normal 11q Number Analyzed 175 participants 96 participants 43 participants
99.4
(98.3 to 100.0)
93.7
(88.7 to 98.7)
87.7
(77.4 to 98.1)
EFS Eligible & evaluable patients w/unbalanced 11q Number Analyzed 0 participants 8 participants 18 participants
75.0
(45.0 to 100.0)
65.5
(42.7 to 88.2)
OS Eligible & evaluable patients w/unbalanced 11q Number Analyzed 0 participants 8 participants 18 participants
87.5
(64.6 to 100.0)
88.2
(72.9 to 100.0)
3.Primary Outcome
Title Comparison Between Reduce Intensity of Therapy for Patients With Stage 4 Neuroblastoma and Favorable Biological Features and Patients < 1 Year of Age With Stage 4 Neuroblastoma Treated on COG-A3961
Hide Description Addressed by the interim stopping rule and the comparison, by INSS stage, to the historical EFS rate of the analogous cohort of patients < 1 yrs of age.
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible and evaluable patients with Stage 4 neuroblastoma, 12-18 months of age, and favorable biological features.
Arm/Group Title Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)
Hide Arm/Group Description:
4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients < 12 months of age with stg 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemo proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
Overall Number of Participants Analyzed 0 9
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of 3 yr EFS rate
66.7
(35.9 to 97.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 3 (Chemotherapy, Surgery), Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)
Comments The event-free survival distributions of patients between 12-18 months of age with Stage 4 neuroblastoma and favorable biological features on ANBL0531 and patients less than 12 months of age with Stage 4 neuroblastoma on A3961 were compared using the log-rank test.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .3212
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Log Rank Test Statistic
Estimated Value .9841
Estimation Comments [Not Specified]
4.Primary Outcome
Title Comparison Between Reduce Intensity of Therapy for Patients With Unfavorable Histology Neuroblastoma and Patients Unfavorable Histology Neuroblastoma Treated on COG-A3961
Hide Description Addressed by the interim stopping rule and the comparison, by INSS stage, to the historical EFS rate of the analogous cohort of patients < 1 yrs of age
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible and evaluable patients with Stage 3 neuroblastoma, 12-18 months of age, MYCN non-amplified, and unfavorable histology.
Arm/Group Title Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)
Hide Arm/Group Description:
4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients < 12 months of age with stg 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemo proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
Overall Number of Participants Analyzed 0 2
Measure Type: Number
Unit of Measure: percentage of 3 yr EFS rate
100
5.Primary Outcome
Title Reduced Surgical Morbidity for Patients With Stage 4S Neuroblastoma
Hide Description Descriptive analyses of the proportion of stage 4S infants that experience a surgical or post-operative event.
Time Frame Up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible and evaluable patients with Stage 4S neuroblastoma that had a biopsy or resection.
Arm/Group Title Group 2 (Chemotherapy, Surgery) Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)
Hide Arm/Group Description:
2 courses of initial chemotherapy (6 wks) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Partial response (PR) to chemo go to observation. No PR: 2-6 additional courses of chemo (beginning course 3 - cyclophosphamide, etoposide, filgrastim, carboplatin, doxorubicin hydrochloride). No PR after additional chemotherapy proceed to retrieval chemo: cyclophosphamide and topotecan hydrochloride on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may also undergo surgery.
4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients < 12 months of age with stg 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemo proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
Overall Number of Participants Analyzed 17 19 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion
0.18
(0.06 to 0.41)
0.11
(0.03 to 0.31)
0
(0 to 0)
6.Primary Outcome
Title Outcome of Patients With Stage 4S Neuroblastoma Who Are Unable to Undergo Biopsy for Biology-based Risk Assignment
Hide Description Kaplan-Meier curves and lifetables of Event Free Survival (EFS) and Overall Survival (OS) rates will be generated to describe the outcome of the stage 4S infants unable to undergo biopsy.
Time Frame From baseline to up to 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible and evaluable patients with Stage 4S neuroblastoma unable to undergo biopsy.
Arm/Group Title Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)
Hide Arm/Group Description:
8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients < 12 months of age with stg 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemo proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
Overall Number of Participants Analyzed 4
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage survival
OS
50.0
(1.0 to 99.0)
EFS
25.0
(0 to 67.4)
7.Primary Outcome
Title Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Event Free Survival (EFS)
Hide Description To test the predictive ability of the extent of surgical resection for EFS, log-rank tests will be performed comparing complete surgical resection vs. without complete surgical resection.
Time Frame Up to 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible and evaluable intermediate risk patients with reported surgery
Arm/Group Title Group 2 (Chemotherapy, Surgery) Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)
Hide Arm/Group Description:
2 courses of initial chemotherapy (6 wks) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Partial response (PR) to chemo go to observation. No PR: 2-6 additional courses of chemo (beginning course 3 - cyclophosphamide, etoposide, filgrastim, carboplatin, doxorubicin hydrochloride). No PR after additional chemotherapy proceed to retrieval chemo: cyclophosphamide and topotecan hydrochloride on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may also undergo surgery.
4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients < 12 months of age with stg 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemo proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
Overall Number of Participants Analyzed 174 137 81
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of 3 yr EFS survival
EFS w/complete surgical resection Number Analyzed 65 participants 43 participants 28 participants
95.4
(90.0 to 100.0)
88.4
(78.7 to 98.1)
78.6
(63.4 to 93.8)
EFS w/o complete surgical resection Number Analyzed 109 participants 94 participants 53 participants
82.2
(74.6 to 89.8)
85.1
(77.7 to 92.4)
69.2
(56.3 to 82.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 2 (Chemotherapy, Surgery), Group 3 (Chemotherapy, Surgery), Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)
Comments The event-free survival distributions of patients with complete surgical resection and patients without complete surgical resection were compared using the log-rank test.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0253
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Log-Rank Test Statistic
Estimated Value 5.0049
Estimation Comments [Not Specified]
8.Primary Outcome
Title Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Overall Survival (OS) Rates
Hide Description To test the predictive ability of the extent of surgical resection for OS, log-rank tests will be performed comparing complete surgical resection vs. without complete surgical resection.
Time Frame Up to 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible and evaluable intermediate risk patients with reported surgery.
Arm/Group Title Group 2 (Chemotherapy, Surgery) Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)
Hide Arm/Group Description:
2 courses of initial chemotherapy (6 wks) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Partial response (PR) to chemo go to observation. No PR: 2-6 additional courses of chemo (beginning course 3 - cyclophosphamide, etoposide, filgrastim, carboplatin, doxorubicin hydrochloride). No PR after additional chemotherapy proceed to retrieval chemo: cyclophosphamide and topotecan hydrochloride on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may also undergo surgery.
4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients < 12 months of age with stg 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemo proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
Overall Number of Participants Analyzed 174 137 81
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of OS rate
OS w/complete surgical resection Number Analyzed 65 participants 43 participants 28 participants
100.0
(100.0 to 100.0)
95.4
(89.0 to 100.0)
96.4
(89.4 to 100.0)
OS w/o complete surgical resection Number Analyzed 109 participants 94 participants 53 participants
99.1
(97.2 to 100.0)
93.5
(88.4 to 98.6)
86.5
(77.0 to 96.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 2 (Chemotherapy, Surgery), Group 3 (Chemotherapy, Surgery), Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)
Comments [Not Specified]
Type of Statistical Test Other
Comments The overall survival distributions of patients with complete surgical resection and patients without complete surgical resection were compared using the log-rank test.
Statistical Test of Hypothesis P-Value .1022
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Log Rank Test Statistic
Estimated Value 2.6709
Estimation Comments [Not Specified]
9.Primary Outcome
Title Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Surgical Complication Rate
Hide Description To test for the association of the extent of surgical resection (CR vs <CR) with surgical complications rate (complications of any kind vs no complications at all), a chi-square test will be performed.
Time Frame Up to 10 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible and evaluable intermediate risk patients with reported surgery
Arm/Group Title Group 2 (Chemotherapy, Surgery) Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)
Hide Arm/Group Description:
2 courses of initial chemotherapy (6 wks) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Partial response (PR) to chemo go to observation. No PR: 2-6 additional courses of chemo (beginning course 3 - cyclophosphamide, etoposide, filgrastim, carboplatin, doxorubicin hydrochloride). No PR after additional chemotherapy proceed to retrieval chemo: cyclophosphamide and topotecan hydrochloride on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may also undergo surgery.
4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients < 12 months of age with stg 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemo proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
Overall Number of Participants Analyzed 174 137 81
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion with surgical complications
CR with complications Number Analyzed 65 participants 43 participants 28 participants
.32
(.22 to .44)
.19
(.10 to .33)
.18
(.08 to .36)
CR with no complications Number Analyzed 109 participants 94 participants 53 participants
.14
(.09 to .21)
.13
(.07 to .21)
.09
(.04 to .20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 2 (Chemotherapy, Surgery), Group 3 (Chemotherapy, Surgery), Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)
Comments The association between extent of surgical resection with occurrence of complications was determined using the chi-square test.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0016
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Chi-Square Test Statistic
Estimated Value 9.9111
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Second-event-free Survival (E2FS)
Hide Description E2FS (from time of first event) will be calculated to describe the outcome for patients who have a first progressive, non-metastatic event during Observation and then receive protocol retrieval therapy.
Time Frame From the time of the first progressive, non-metastatic event until the subsequent occurrence of relapse, progressive disease, secondary malignancy, or death; up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients who have a first progressive, non-metastatic event during Observation and then receive protocol retrieval therapy
Arm/Group Title All Patients
Hide Arm/Group Description:
All eligible patients who have a first progressive, non-metastatic event during Observation and then receive protocol retrieval therapy
Overall Number of Participants Analyzed 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage
57.14
(20.49 to 93.79)
11.Secondary Outcome
Title Second-Overall Survival
Hide Description OS (from the time of first event) will be calculated to describe the outcome for patients who have a first progressive, non-metastatic event during Observation and then receive protocol retrieval therapy.
Time Frame From the time of the first progressive, non-metastatic event; up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients who have a first progressive, non-metastatic event during Observation and then receive protocol retrieval therapy.
Arm/Group Title All Patients
Hide Arm/Group Description:
All eligible patients who have a first progressive, non-metastatic event during Observation and then receive protocol retrieval therapy
Overall Number of Participants Analyzed 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage
85.71
(59.78 to 100)
12.Secondary Outcome
Title Biological Surrogate Markers
Hide Description Multivariable analyses will be performed to identify variables of prognostic interest.
Time Frame At baseline and surgery
Hide Outcome Measure Data
Hide Analysis Population Description
The data was not collected to assess this study aim.
Arm/Group Title Group 2 (Chemotherapy, Surgery) Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)
Hide Arm/Group Description:
2 courses of initial chemotherapy (6 wks) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Partial response (PR) to chemo go to observation. No PR: 2-6 additional courses of chemo (beginning course 3 - cyclophosphamide, etoposide, filgrastim, carboplatin, doxorubicin hydrochloride). No PR after additional chemotherapy proceed to retrieval chemo: cyclophosphamide and topotecan hydrochloride on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may also undergo surgery.
4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients < 12 months of age with stg 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemo proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
13.Secondary Outcome
Title Neurologic Symptoms
Hide Description Percentage of patients with neurologic symptoms will be calculated. Includes patients with paraspinal or intraspinal tumors, including epidural tumors with or without spinal cord compression. Neurologic symptoms include back or extremities neurologic symptoms, motor deficit, abnormal sensation, abnormal bladder/bowel sphincteric function, chronic pain in back or extremities, scoliosis, kyphosis, or clinically relevant/functional abnormality in size or contour of leg or foot.
Time Frame At baseline
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible and evaluable patients enrolled on ANBL0531
Arm/Group Title Group 2 (Chemotherapy, Surgery) Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)
Hide Arm/Group Description:
2 courses of initial chemotherapy (6 wks) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Partial response (PR) to chemo go to observation. No PR: 2-6 additional courses of chemo (beginning course 3 - cyclophosphamide, etoposide, filgrastim, carboplatin, doxorubicin hydrochloride). No PR after additional chemotherapy proceed to retrieval chemo: cyclophosphamide and topotecan hydrochloride on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may also undergo surgery.
4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients < 12 months of age with stg 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemo proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
Overall Number of Participants Analyzed 175 141 88
Measure Type: Number
Unit of Measure: percentage of patients
36.57 35.46 27.27
14.Secondary Outcome
Title Association Between Surgical Biopsy Technique With Adequacy of Tissue Acquisition for Biologic Studies, and With Complications Associated With the Biopsy Procedure
Hide Description A chi-square test will be performed.
Time Frame During and after surgery
Hide Outcome Measure Data
Hide Analysis Population Description
The data was not collected to assess this study aim.
Arm/Group Title Group 2 (Chemotherapy, Surgery) Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)
Hide Arm/Group Description:
2 courses of initial chemotherapy (6 wks) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Partial response (PR) to chemo go to observation. No PR: 2-6 additional courses of chemo (beginning course 3 - cyclophosphamide, etoposide, filgrastim, carboplatin, doxorubicin hydrochloride). No PR after additional chemotherapy proceed to retrieval chemo: cyclophosphamide and topotecan hydrochloride on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may also undergo surgery.
4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients < 12 months of age with stg 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemo proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
15.Secondary Outcome
Title Image Defined Risk Factor (IDRF)
Hide Description Percentage of patients with presence of one or more IDRFs will be calculated. IDRFs describe anatomic features which may make surgical resection more difficult.
Time Frame At baseline
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible and evaluable patients enrolled on ANBL0531
Arm/Group Title Group 2 (Chemotherapy, Surgery) Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)
Hide Arm/Group Description:
2 courses of initial chemotherapy (6 wks) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Partial response (PR) to chemo go to observation. No PR: 2-6 additional courses of chemo (beginning course 3 - cyclophosphamide, etoposide, filgrastim, carboplatin, doxorubicin hydrochloride). No PR after additional chemotherapy proceed to retrieval chemo: cyclophosphamide and topotecan hydrochloride on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may also undergo surgery.
4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients < 12 months of age with stg 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemo proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.
Overall Number of Participants Analyzed 175 141 88
Measure Type: Number
Unit of Measure: percentage of patients
54.86 60.28 56.82
Time Frame [Not Specified]
Adverse Event Reporting Description SAE field contains NCI CTCAEs submitted via expedited reporting (NCI AdEERs / CAeRs). The AE field contains grade 3 and higher CTCAEs reported on study excluding those that were reported as SAEs.
 
Arm/Group Title Group 2 (Chemotherapy, Surgery) Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy) Non-intermediate Risk Enrolled on Intermediate Risk Trial
Hide Arm/Group Description 2 courses of initial chemotherapy (6 wks) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Partial response (PR) to chemo go to observation. No PR: 2-6 additional courses of chemo (beginning course 3 - cyclophosphamide, etoposide, filgrastim, carboplatin, doxorubicin hydrochloride). No PR after additional chemotherapy proceed to retrieval chemo: cyclophosphamide and topotecan hydrochloride on days 1-5. Treatment with retrieval chemotherapy repeats every 21 days for up to 6 courses. Some patients may also undergo surgery. 4 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, filgrastim. Patients with a PR after chemo proceed to observation. No PR receive 2-4 additional courses of chemotherapy (beginning with course 5) - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. No PR after additional chemo proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery. 8 courses of initial chemo - carboplatin, cyclophosphamide, doxorubicin hydrochloride, etoposide, filgrastim. Patients < 12 months of age with stg 3, 4, or 4S (not including liver metastases) disease who achieve a very good PR (VGPR) to chemo proceed to observation. Patients 12-18 months of age with stg 3 or 4 who achieve VGPR proceed to isotretinoin therapy. No VGPR proceed to retrieval chemo - cyclophosphamide and topotecan hydrochloride. Some patients may also undergo surgery.

The no treatment group assignment patients may have received some treatment on ANBL0531 but they were not evaluable on this study due to being non-intermediate risk and hence did not receive a treatment assignment on ANBL0531.

Surgery: With the exception of patients with INSS 4S disease, patients undergo surgery to remove as much of the primary tumor and involved lymph nodes as can safely be accomplished.

All-Cause Mortality
Group 2 (Chemotherapy, Surgery) Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy) Non-intermediate Risk Enrolled on Intermediate Risk Trial
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Group 2 (Chemotherapy, Surgery) Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy) Non-intermediate Risk Enrolled on Intermediate Risk Trial
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/175 (1.14%)      5/140 (3.57%)      8/89 (8.99%)      1/42 (2.38%)    
Blood and lymphatic system disorders         
13200-Anemia  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  3 0/42 (0.00%)  0
Gastrointestinal disorders         
46300-Intra-abdominal hemorrhage  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
General disorders         
24600-Death NOS  0/175 (0.00%)  0 2/140 (1.43%)  2 1/89 (1.12%)  1 0/42 (0.00%)  0
55700-Multi-organ failure  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
Hepatobiliary disorders         
40600-Hepatobiliary disorders - Other specify  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 1/42 (2.38%)  1
Infections and infestations         
44800-Infections and infestations - Other specify  2/175 (1.14%)  2 1/140 (0.71%)  1 2/89 (2.25%)  2 0/42 (0.00%)  0
73700-Sepsis  0/175 (0.00%)  0 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
Injury, poisoning and procedural complications         
80700-Tracheal obstruction  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
Investigations         
17400-Blood bilirubin increased  0/175 (0.00%)  0 0/140 (0.00%)  0 2/89 (2.25%)  2 0/42 (0.00%)  0
58300-Neutrophil count decreased  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
65800-Platelet count decreased  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  3 0/42 (0.00%)  0
Metabolism and nutrition disorders         
10700-Acidosis  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
Renal and urinary disorders         
11100-Acute kidney injury  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 1/42 (2.38%)  1
71000-Renal and urinary disorders - Other specify  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
19200-Bronchopulmonary hemorrhage  0/175 (0.00%)  0 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
43900-Hypoxia  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
71500-Respiratory failure  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
71600-Respiratory thoracic and mediastinal disorders - Other specify  0/175 (0.00%)  0 0/140 (0.00%)  0 0/89 (0.00%)  0 1/42 (2.38%)  1
Vascular disorders         
43600-Hypotension  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
1
Term from vocabulary, CTCv4
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Group 2 (Chemotherapy, Surgery) Group 3 (Chemotherapy, Surgery) Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy) Non-intermediate Risk Enrolled on Intermediate Risk Trial
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   135/175 (77.14%)      114/140 (81.43%)      76/89 (85.39%)      23/42 (54.76%)    
Blood and lymphatic system disorders         
13200-Anemia  60/175 (34.29%)  94 64/140 (45.71%)  102 45/89 (50.56%)  105 14/42 (33.33%)  14
17200-Blood and lymphatic system disorders - Other specify  0/175 (0.00%)  0 0/140 (0.00%)  0 2/89 (2.25%)  2 1/42 (2.38%)  1
25800-Disseminated intravascular coagulation  0/175 (0.00%)  0 2/140 (1.43%)  2 0/89 (0.00%)  0 0/42 (0.00%)  0
33300-Febrile neutropenia  24/175 (13.71%)  28 22/140 (15.71%)  27 17/89 (19.10%)  20 1/42 (2.38%)  1
Cardiac disorders         
20000-Cardiac arrest  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
51700-Left ventricular systolic dysfunction  0/175 (0.00%)  0 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
87100-Ventricular tachycardia  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
Ear and labyrinth disorders         
55000-Middle ear inflammation  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
Endocrine disorders         
29200-Endocrine disorders - Other specify  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
Eye disorders         
31900-Eye disorders - Other specify  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
Gastrointestinal disorders         
10100-Abdominal distension  1/175 (0.57%)  1 1/140 (0.71%)  1 0/89 (0.00%)  0 2/42 (4.76%)  2
10300-Abdominal pain  3/175 (1.71%)  3 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
14900-Ascites  2/175 (1.14%)  2 1/140 (0.71%)  1 2/89 (2.25%)  2 1/42 (2.38%)  1
25700-Diarrhea  6/175 (3.43%)  6 4/140 (2.86%)  4 5/89 (5.62%)  10 2/42 (4.76%)  2
27600-Dysphagia  0/175 (0.00%)  0 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
36700-Gastrointestinal disorders - Other specify  0/175 (0.00%)  0 1/140 (0.71%)  1 1/89 (1.12%)  5 0/42 (0.00%)  0
37600-Gingival pain  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
44600-Ileus  0/175 (0.00%)  0 1/140 (0.71%)  1 2/89 (2.25%)  2 0/42 (0.00%)  0
46300-Intra-abdominal hemorrhage  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
49400-Jejunal stenosis  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
53900-Malabsorption  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
55600-Mucositis oral  0/175 (0.00%)  0 0/140 (0.00%)  0 2/89 (2.25%)  2 0/42 (0.00%)  0
57600-Nausea  0/175 (0.00%)  0 1/140 (0.71%)  1 1/89 (1.12%)  1 0/42 (0.00%)  0
75700-Small intestinal obstruction  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
75900-Small intestinal stenosis  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
81900-Typhlitis  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
87900-Vomiting  5/175 (2.86%)  5 3/140 (2.14%)  3 4/89 (4.49%)  4 1/42 (2.38%)  1
General disorders         
28200-Edema face  0/175 (0.00%)  0 0/140 (0.00%)  0 0/89 (0.00%)  0 1/42 (2.38%)  1
28300-Edema limbs  0/175 (0.00%)  0 0/140 (0.00%)  0 0/89 (0.00%)  0 1/42 (2.38%)  1
28400-Edema trunk  0/175 (0.00%)  0 0/140 (0.00%)  0 0/89 (0.00%)  0 1/42 (2.38%)  1
33900-Fever  2/175 (1.14%)  2 1/140 (0.71%)  1 4/89 (4.49%)  4 0/42 (0.00%)  0
34600-Flu like symptoms  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
35000-Gait disturbance  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
37200-General disorders and administration site conditions - Other specify  0/175 (0.00%)  0 2/140 (1.43%)  2 0/89 (0.00%)  0 0/42 (0.00%)  0
43700-Hypothermia  0/175 (0.00%)  0 0/140 (0.00%)  0 0/89 (0.00%)  0 1/42 (2.38%)  1
48700-Irritability  0/175 (0.00%)  0 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
58600-Non-cardiac chest pain  0/175 (0.00%)  0 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
60600-Pain  2/175 (1.14%)  2 3/140 (2.14%)  4 1/89 (1.12%)  1 1/42 (2.38%)  1
Hepatobiliary disorders         
35400-Gallbladder obstruction  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
40000-Hepatic failure  0/175 (0.00%)  0 1/140 (0.71%)  2 0/89 (0.00%)  0 1/42 (2.38%)  1
66600-Portal vein thrombosis  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
Immune system disorders         
13100-Anaphylaxis  4/175 (2.29%)  4 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
Infections and infestations         
10200-Abdominal infection  1/175 (0.57%)  1 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
16600-Biliary tract infection  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  2 0/42 (0.00%)  0
16800-Bladder infection  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
18800-Bronchial infection  0/175 (0.00%)  0 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
20500-Catheter related infection  3/175 (1.71%)  4 7/140 (5.00%)  7 6/89 (6.74%)  6 0/42 (0.00%)  0
29500-Enterocolitis infectious  3/175 (1.71%)  3 1/140 (0.71%)  1 2/89 (2.25%)  2 0/42 (0.00%)  0
32000-Eye infection  0/175 (0.00%)  0 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
38300-Gum infection  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
44800-Infections and infestations - Other specify  32/175 (18.29%)  50 19/140 (13.57%)  26 34/89 (38.20%)  60 6/42 (14.29%)  9
50300-Kidney infection  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
53100-Lung infection  2/175 (1.14%)  2 3/140 (2.14%)  3 2/89 (2.25%)  2 0/42 (0.00%)  0
60100-Otitis media  0/175 (0.00%)  0 0/140 (0.00%)  0 3/89 (3.37%)  3 1/42 (2.38%)  1
69800-Rash pustular  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
72600-Rhinitis infective  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
75200-Skin infection  3/175 (1.71%)  3 0/140 (0.00%)  0 2/89 (2.25%)  2 0/42 (0.00%)  0
80900-Tracheitis  0/175 (0.00%)  0 3/140 (2.14%)  5 0/89 (0.00%)  0 1/42 (2.38%)  1
82300-Upper respiratory infection  1/175 (0.57%)  1 2/140 (1.43%)  4 3/89 (3.37%)  3 0/42 (0.00%)  0
83100-Urinary tract infection  5/175 (2.86%)  5 1/140 (0.71%)  1 4/89 (4.49%)  5 0/42 (0.00%)  0
88900-Wound infection  1/175 (0.57%)  1 1/140 (0.71%)  1 3/89 (3.37%)  3 0/42 (0.00%)  0
Injury, poisoning and procedural complications         
14500-Arterial injury  0/175 (0.00%)  0 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
86400-Vascular access complication  0/175 (0.00%)  0 1/140 (0.71%)  1 2/89 (2.25%)  2 0/42 (0.00%)  0
Investigations         
10900-Activated partial thromboplastin time prolonged  3/175 (1.71%)  3 4/140 (2.86%)  5 3/89 (3.37%)  3 1/42 (2.38%)  1
11600-Alanine aminotransferase increased  4/175 (2.29%)  4 7/140 (5.00%)  9 8/89 (8.99%)  11 1/42 (2.38%)  1
11800-Alkaline phosphatase increased  1/175 (0.57%)  3 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
15000-Aspartate aminotransferase increased  2/175 (1.14%)  2 8/140 (5.71%)  9 11/89 (12.36%)  14 4/42 (9.52%)  4
17400-Blood bilirubin increased  2/175 (1.14%)  2 10/140 (7.14%)  11 6/89 (6.74%)  7 2/42 (4.76%)  2
34000-Fibrinogen decreased  0/175 (0.00%)  0 3/140 (2.14%)  3 2/89 (2.25%)  2 1/42 (2.38%)  1
37500-GGT increased  0/175 (0.00%)  0 1/140 (0.71%)  1 1/89 (1.12%)  1 1/42 (2.38%)  1
45800-INR increased  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 2/42 (4.76%)  2
52600-Lipase increased  0/175 (0.00%)  0 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
53700-Lymphocyte count decreased  11/175 (6.29%)  14 11/140 (7.86%)  11 14/89 (15.73%)  28 1/42 (2.38%)  1
58300-Neutrophil count decreased  99/175 (56.57%)  173 86/140 (61.43%)  178 55/89 (61.80%)  156 13/42 (30.95%)  13
65800-Platelet count decreased  57/175 (32.57%)  79 56/140 (40.00%)  85 40/89 (44.94%)  75 9/42 (21.43%)  9
88300-Weight loss  1/175 (0.57%)  1 0/140 (0.00%)  0 2/89 (2.25%)  2 1/42 (2.38%)  1
88500-White blood cell decreased  47/175 (26.86%)  72 60/140 (42.86%)  89 36/89 (40.45%)  72 8/42 (19.05%)  8
Metabolism and nutrition disorders         
10700-Acidosis  1/175 (0.57%)  1 3/140 (2.14%)  4 0/89 (0.00%)  0 3/42 (7.14%)  3
11900-Alkalosis  0/175 (0.00%)  0 1/140 (0.71%)  2 0/89 (0.00%)  0 0/42 (0.00%)  0
13500-Anorexia  8/175 (4.57%)  8 9/140 (6.43%)  16 4/89 (4.49%)  9 2/42 (4.76%)  2
24700-Dehydration  3/175 (1.71%)  3 2/140 (1.43%)  2 5/89 (5.62%)  5 0/42 (0.00%)  0
41300-Hypercalcemia  1/175 (0.57%)  1 1/140 (0.71%)  2 1/89 (1.12%)  1 3/42 (7.14%)  3
41400-Hyperglycemia  6/175 (3.43%)  7 7/140 (5.00%)  7 3/89 (3.37%)  5 2/42 (4.76%)  2
41600-Hyperkalemia  3/175 (1.71%)  3 5/140 (3.57%)  5 1/89 (1.12%)  1 1/42 (2.38%)  1
41700-Hypermagnesemia  0/175 (0.00%)  0 0/140 (0.00%)  0 0/89 (0.00%)  0 1/42 (2.38%)  1
41800-Hypernatremia  0/175 (0.00%)  0 0/140 (0.00%)  0 0/89 (0.00%)  0 2/42 (4.76%)  2
42500-Hyperuricemia  0/175 (0.00%)  0 1/140 (0.71%)  1 1/89 (1.12%)  1 2/42 (4.76%)  2
42600-Hypoalbuminemia  5/175 (2.86%)  5 6/140 (4.29%)  7 6/89 (6.74%)  7 1/42 (2.38%)  1
42700-Hypocalcemia  5/175 (2.86%)  5 2/140 (1.43%)  2 4/89 (4.49%)  4 2/42 (4.76%)  2
42900-Hypoglycemia  1/175 (0.57%)  1 3/140 (2.14%)  3 3/89 (3.37%)  4 2/42 (4.76%)  2
43100-Hypokalemia  8/175 (4.57%)  10 13/140 (9.29%)  15 15/89 (16.85%)  18 2/42 (4.76%)  2
43300-Hyponatremia  6/175 (3.43%)  6 5/140 (3.57%)  5 6/89 (6.74%)  6 1/42 (2.38%)  1
43500-Hypophosphatemia  2/175 (1.14%)  2 1/140 (0.71%)  1 0/89 (0.00%)  0 2/42 (4.76%)  2
81700-Tumor lysis syndrome  0/175 (0.00%)  0 0/140 (0.00%)  0 0/89 (0.00%)  0 1/42 (2.38%)  1
Musculoskeletal and connective tissue disorders         
16200-Back pain  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
38700-Head soft tissue necrosis  0/175 (0.00%)  0 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
55900-Muscle weakness lower limb  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  4 0/42 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
58000-Neoplasms benign malignant and unspecified (incl cysts and polyps) - Other specify  1/175 (0.57%)  2 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
81800-Tumor pain  0/175 (0.00%)  0 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
Nervous system disorders         
22000-Cognitive disturbance  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
25300-Depressed level of consciousness  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
27700-Dysphasia  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
29000-Encephalopathy  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
58100-Nervous system disorders - Other specify  1/175 (0.57%)  1 2/140 (1.43%)  3 0/89 (0.00%)  0 0/42 (0.00%)  0
63900-Peripheral motor neuropathy  1/175 (0.57%)  1 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
64100-Peripheral sensory neuropathy  0/175 (0.00%)  0 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
70900-Recurrent laryngeal nerve palsy  0/175 (0.00%)  0 1/140 (0.71%)  2 0/89 (0.00%)  0 0/42 (0.00%)  0
73600-Seizure  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
Renal and urinary disorders         
11100-Acute kidney injury  0/175 (0.00%)  0 3/140 (2.14%)  3 1/89 (1.12%)  1 1/42 (2.38%)  1
68300-Proteinuria  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
83000-Urinary retention  0/175 (0.00%)  0 2/140 (1.43%)  2 1/89 (1.12%)  1 0/42 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
11300-Adult respiratory distress syndrome  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 1/42 (2.38%)  1
14100-Apnea  0/175 (0.00%)  0 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
15100-Aspiration  1/175 (0.57%)  1 0/140 (0.00%)  0 1/89 (1.12%)  1 0/42 (0.00%)  0
15400-Atelectasis  0/175 (0.00%)  0 2/140 (1.43%)  2 0/89 (0.00%)  0 1/42 (2.38%)  1
19200-Bronchopulmonary hemorrhage  0/175 (0.00%)  0 2/140 (1.43%)  3 0/89 (0.00%)  0 0/42 (0.00%)  0
19300-Bronchospasm  0/175 (0.00%)  0 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
21900-Chylothorax  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
27800-Dyspnea  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 1/42 (2.38%)  1
43900-Hypoxia  6/175 (3.43%)  6 5/140 (3.57%)  5 2/89 (2.25%)  3 1/42 (2.38%)  1
65900-Pleural effusion  2/175 (1.14%)  2 1/140 (0.71%)  1 2/89 (2.25%)  2 1/42 (2.38%)  1
66300-Pneumonitis  0/175 (0.00%)  0 0/140 (0.00%)  0 0/89 (0.00%)  0 1/42 (2.38%)  1
66400-Pneumothorax  0/175 (0.00%)  0 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
71600-Respiratory thoracic and mediastinal disorders - Other specify  1/175 (0.57%)  1 4/140 (2.86%)  5 2/89 (2.25%)  2 1/42 (2.38%)  1
Skin and subcutaneous tissue disorders         
60800-Pain of skin  0/175 (0.00%)  0 1/140 (0.71%)  1 0/89 (0.00%)  0 0/42 (0.00%)  0
74700-Skin and subcutaneous tissue disorders - Other specify  0/175 (0.00%)  0 1/140 (0.71%)  2 0/89 (0.00%)  0 0/42 (0.00%)  0
84100-Urticaria  1/175 (0.57%)  2 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
Vascular disorders         
19800-Capillary leak syndrome  0/175 (0.00%)  0 0/140 (0.00%)  0 1/89 (1.12%)  1 1/42 (2.38%)  1
39100-Hematoma  0/175 (0.00%)  0 0/140 (0.00%)  0 0/89 (0.00%)  0 1/42 (2.38%)  1
42100-Hypertension  5/175 (2.86%)  6 2/140 (1.43%)  3 6/89 (6.74%)  15 1/42 (2.38%)  1
43600-Hypotension  1/175 (0.57%)  2 3/140 (2.14%)  3 0/89 (0.00%)  0 3/42 (7.14%)  3
53300-Lymph leakage  1/175 (0.57%)  1 0/140 (0.00%)  0 0/89 (0.00%)  0 0/42 (0.00%)  0
79600-Thromboembolic event  0/175 (0.00%)  0 0/140 (0.00%)  0 2/89 (2.25%)  2 0/42 (0.00%)  0
1
Term from vocabulary, CTCv4
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Must obtain prior Sponsor approval.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 626-447-0064
EMail: resultsreportingcoordinator@childrensoncologygroup.org
Layout table for additonal information
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00499616     History of Changes
Other Study ID Numbers: ANBL0531
COG-ANBL0531 ( Other Identifier: Children's Oncology Group )
NCI-2009-00400 ( Other Identifier: CTRP (Clinical Trial Reporting Program) )
First Submitted: July 10, 2007
First Posted: July 11, 2007
Results First Submitted: December 1, 2015
Results First Posted: June 27, 2017
Last Update Posted: June 21, 2019