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Regorafenib+FOLFIRI Versus Placebo+FOLFIRI as 2nd Line Tx in Metastatic Colorectal Cancer

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ClinicalTrials.gov Identifier: NCT01298570
Recruitment Status : Active, not recruiting
First Posted : February 17, 2011
Results First Posted : February 28, 2018
Last Update Posted : July 4, 2019
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Colorectal Cancer Metastatic
Interventions Drug: Regorafenib (BAY 73-4506)
Drug: FOLFIRI
Drug: Placebo
Enrollment 181
Recruitment Details 224 participants were consented to the study from 39 institutions from 4/7/11 - 8/10/15.
Pre-assignment Details 30 participants were ineligible, 7 withdrew prior to beginning protocol therapy, 3 could not participate due to study closure, 2 were unable to participate for financial reasons, 1 did not provide a reason for non-participation; 181 patients were enrolled and went on treatment.
Arm/Group Title Arm A Arm B
Hide Arm/Group Description

regorafenib 160 mg + FOLFIRI

Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Placebo + FOLFIRI

Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Period Title: Overall Study
Started 120 61
Completed [1] 0 0
Not Completed 120 61
Reason Not Completed
Disease progression, relapse during acti             64             40
Adverse Event             20             2
Withdrawal by Subject             21             6
Treatment delay > 4 weeks             4             5
Physician Decision             4             2
Other complicating disease             2             1
Surgery             2             1
Symptomatic progression/deterioration             3             2
Death             0             1
Ineligibility             0             1
[1]
Patients treated until progression
Arm/Group Title Arm A Arm B Total
Hide Arm/Group Description

regorafenib 160 mg + FOLFIRI

Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Placebo + FOLFIRI

Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Total of all reporting groups
Overall Number of Baseline Participants 120 61 181
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 120 participants 61 participants 181 participants
62
(30 to 94)
62
(30 to 82)
62
(30 to 94)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 120 participants 61 participants 181 participants
Female
52
  43.3%
29
  47.5%
81
  44.8%
Male
68
  56.7%
32
  52.5%
100
  55.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 120 participants 61 participants 181 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
20
  16.7%
11
  18.0%
31
  17.1%
White
99
  82.5%
48
  78.7%
147
  81.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   0.8%
2
   3.3%
3
   1.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Count of participants
Number Analyzed 120 participants 61 participants 181 participants
United States 84 43 127
Ireland 36 18 54
ECOG Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 120 participants 61 participants 181 participants
0
52
  43.3%
23
  37.7%
75
  41.4%
1
68
  56.7%
38
  62.3%
106
  58.6%
[1]
Measure Description:

A scale by the Eastern Cooperative Oncology Group (ECOG) from 0-5 to describe patient's selfcare ability and activity level.

0, Fully active

  1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature
  2. Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
  3. Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
  4. Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
  5. Dead
Stage at diagnosis   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 120 participants 61 participants 181 participants
I
3
   2.5%
0
   0.0%
3
   1.7%
II
4
   3.3%
4
   6.6%
8
   4.4%
III
24
  20.0%
11
  18.0%
35
  19.3%
IV
86
  71.7%
46
  75.4%
132
  72.9%
Unknown
3
   2.5%
0
   0.0%
3
   1.7%
[1]
Measure Description: Stages I, II, III indicate that cancer is present, and the higher the number the larger the cancer tumor and the more it has spread into nearby tissues. Stage IV indicates that cancer has spread to distant parts of the body.
Prior Biologic Agent  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 120 participants 61 participants 181 participants
None
33
  27.5%
16
  26.2%
49
  27.1%
Bevacizumab
76
  63.3%
41
  67.2%
117
  64.6%
EGFR inhibitor
11
   9.2%
4
   6.6%
15
   8.3%
Locally Reported RAS   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 120 participants 61 participants 181 participants
Wildtype
49
  40.8%
18
  29.5%
67
  37.0%
Mutated
54
  45.0%
37
  60.7%
91
  50.3%
Unknown
17
  14.2%
6
   9.8%
23
  12.7%
[1]
Measure Description: The 3 Ras genes in humans (HRas, KRas, and NRas) are the most common oncogenes in human cancer; some therapies are more effective with nonmutated wildtype genes.
Locally Reported BRAF   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 120 participants 61 participants 181 participants
Wildtype
22
  18.3%
12
  19.7%
34
  18.8%
Mutated
10
   8.3%
2
   3.3%
12
   6.6%
Unknown
88
  73.3%
47
  77.0%
135
  74.6%
[1]
Measure Description: Many mutations of the BRAF gene are associated with cancer. Some drugs are designed to work with mutated forms of the gene.
1.Primary Outcome
Title Progression Free Survival (PFS)
Hide Description To compare PFS between regorafenib + FOLFIRI chemotherapy (ARM A) versus placebo + FOLFIRI (ARM B) in patients failing one prior oxaliplatin-containing regimen for metastatic colorectal cancer. PFS is defined as the time from randomization until metastatic colorectal cancer (mCRC) progression or death as a result of any cause. Radiographic response will be measured by RECIST, Response Evaluation Criteria In Solid Tumors Criteria, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame 5.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm A Arm B
Hide Arm/Group Description:

regorafenib 160 mg + FOLFIRI

Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Placebo + FOLFIRI

Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Overall Number of Participants Analyzed 120 61
Median (95% Confidence Interval)
Unit of Measure: Months
6.1
(5.5 to 7.3)
5.3
(4.1 to 6.0)
2.Secondary Outcome
Title Overall Response(OR)Rate
Hide Description To compare overall response (OR) rates (OR= CR + PR) between ARM A and ARM B as defined via Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Only evaluable participants (those who had RECIST measurements after baseline) were included in this analysis
Arm/Group Title Arm A Arm B
Hide Arm/Group Description:

regorafenib 160 mg + FOLFIRI

Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Placebo + FOLFIRI

Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Overall Number of Participants Analyzed 102 58
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response (CR)
0
   0.0%
0
   0.0%
Partial Response (PR)
35
  34.3%
12
  20.7%
Other
67
  65.7%
46
  79.3%
3.Secondary Outcome
Title Disease Control (DC) Rate
Hide Description To compare Disease Control (DC) Rate (DC= CR + PR + SD) between ARM A and ARM B as defined via Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions and Stable Disease (SD) ), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Only evaluable participants (those who had RECIST measurements after baseline) were included in this analysis
Arm/Group Title Arm A Arm B
Hide Arm/Group Description:

regorafenib 160 mg + FOLFIRI

Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Placebo + FOLFIRI

Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Overall Number of Participants Analyzed 102 58
Measure Type: Count of Participants
Unit of Measure: Participants
Disease Control Total (CR+PR+SD)
84
  82.4%
43
  74.1%
Progression
18
  17.6%
15
  25.9%
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description To compare overall survival (OS) between ARM A and ARM B. OS is defined as the time from randomization until death as a result of any cause.
Time Frame 5.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm A Arm B
Hide Arm/Group Description:

regorafenib 160 mg + FOLFIRI

Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Placebo + FOLFIRI

Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Overall Number of Participants Analyzed 120 61
Median (Full Range)
Unit of Measure: Months
13.8
(10.5 to 14.8)
11.7
(9.0 to 15.9)
5.Secondary Outcome
Title Drug Metabolism
Hide Description To compare the pharmacokinetic (PK) profile of FOLFIRI between a subset of patients receiving regorafenib (ARM A) and patients receiving placebo (Arm B). The Area Under the Curve (AUC) levels of the irinotecan metabolite SN-38 were compared.
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
This objective was designed to only look at a small subset of participants (11 on each arm)
Arm/Group Title Arm A Arm B
Hide Arm/Group Description:

regorafenib 160 mg + FOLFIRI

Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Placebo + FOLFIRI

Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Overall Number of Participants Analyzed 11 11
Median (Inter-Quartile Range)
Unit of Measure: AUC/dose=(ng/mL*h)/(mg/m^2)
Cycle 1
0.68
(0.49 to 0.89)
0.63
(0.47 to 0.91)
Cycle 2
0.59
(0.24 to 0.85)
0.72
(0.47 to 0.91)
6.Secondary Outcome
Title Percentage of Patients With Severe Adverse Events
Hide Description Toxicity Assessments were made according to NCI CTCAE v. 4.0 . Severe events (grades 3-4) that occurred in a higher percentage of regorafenib treated participants as compared to placebo are reported below.
Time Frame 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received treatment
Arm/Group Title Arm A Arm B
Hide Arm/Group Description:

regorafenib 160 mg + FOLFIRI

Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Placebo + FOLFIRI

Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Overall Number of Participants Analyzed 120 61
Measure Type: Number
Unit of Measure: percentage of participants
neutropenia 41 30
diarrhea 15 5
hypophosphatemia 14 0
hypertension 8 2
elevated lipase 8 3
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm A Arm B
Hide Arm/Group Description

regorafenib 160 mg + FOLFIRI

Regorafenib (BAY 73-4506): Regorafenib, 160 mg, PO, daily, per 7 day cycle

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

Placebo + FOLFIRI

Placebo: Placebo, oral administration, Days 4-10 and Days 18-24 of 28 day cycle +

FOLFIRI: FOLFIRI (Irinotecan,180 mg/m2 IV over 90 minutes; 5-Fluorouracil l400 mg/m2 IV bolus followed by 2400 mg/m2 IV over 46 hours; Leucovorin 200-400c mg/m2 IV over 2 hours) Day 1 and Day 15 of each 28 day cycle.

All-Cause Mortality
Arm A Arm B
Affected / at Risk (%) Affected / at Risk (%)
Total   112/120 (93.33%)   59/61 (96.72%) 
Show Serious Adverse Events Hide Serious Adverse Events
Arm A Arm B
Affected / at Risk (%) Affected / at Risk (%)
Total   60/120 (50.00%)   20/61 (32.79%) 
Blood and lymphatic system disorders     
Anemia * 1  2/120 (1.67%)  3/61 (4.92%) 
Febrile neutropenia * 1  7/120 (5.83%)  3/61 (4.92%) 
Cardiac disorders     
Chest pain - cardiac * 1  2/120 (1.67%)  1/61 (1.64%) 
Atrial fibrillation * 1  1/120 (0.83%)  0/61 (0.00%) 
Sinus bradicardia * 1  1/120 (0.83%)  0/61 (0.00%) 
Left ventricular systolic dysfunction * 1  1/120 (0.83%)  0/61 (0.00%) 
Palpitations * 1  1/120 (0.83%)  0/61 (0.00%) 
Ventricular tachycardia * 1  1/120 (0.83%)  0/61 (0.00%) 
Endocrine disorders     
Hypothyroidism * 1  0/120 (0.00%)  1/61 (1.64%) 
Gastrointestinal disorders     
Abdominal pain * 1  9/120 (7.50%)  2/61 (3.28%) 
Ascites * 1  0/120 (0.00%)  1/61 (1.64%) 
Colitis * 1  1/120 (0.83%)  0/61 (0.00%) 
Constipation * 1  1/120 (0.83%)  2/61 (3.28%) 
Colonic hemorrhage * 1  1/120 (0.83%)  0/61 (0.00%) 
Colonic obstruction * 1  1/120 (0.83%)  0/61 (0.00%) 
Colonic perforation * 1  1/120 (0.83%)  0/61 (0.00%) 
Diarrhea * 1  10/120 (8.33%)  1/61 (1.64%) 
Esophageal varices hemorrhage * 1  0/120 (0.00%)  1/61 (1.64%) 
Ileus * 1  3/120 (2.50%)  0/61 (0.00%) 
Mucositis oral * 1  3/120 (2.50%)  1/61 (1.64%) 
Nausea * 1  2/120 (1.67%)  1/61 (1.64%) 
Vomiting * 1  0/120 (0.00%)  2/61 (3.28%) 
Rectal hemorrhage * 1  4/120 (3.33%)  0/61 (0.00%) 
Small intestinal perforation * 1  1/120 (0.83%)  0/61 (0.00%) 
General disorders     
Chills * 1  0/120 (0.00%)  1/61 (1.64%) 
Death NOS * 1  2/120 (1.67%)  2/61 (3.28%) 
Fatigue * 1  2/120 (1.67%)  1/61 (1.64%) 
Fever * 1  9/120 (7.50%)  3/61 (4.92%) 
flu like symptoms * 1  1/120 (0.83%)  0/61 (0.00%) 
Pressure in Head * 1  1/120 (0.83%)  0/61 (0.00%) 
Rigors * 1  1/120 (0.83%)  0/61 (0.00%) 
Generalized muscle weakness * 1  1/120 (0.83%)  0/61 (0.00%) 
Pain * 1  1/120 (0.83%)  1/61 (1.64%) 
Infusion related reaction * 1  1/120 (0.83%)  0/61 (0.00%) 
Non-cardiac chest pain * 1  1/120 (0.83%)  0/61 (0.00%) 
Hepatobiliary disorders     
Cholecystitis * 1  3/120 (2.50%)  1/61 (1.64%) 
Hepatic failure * 1  1/120 (0.83%)  0/61 (0.00%) 
Cholangitis * 1  1/120 (0.83%)  0/61 (0.00%) 
Infections and infestations     
Abdominal infection * 1  1/120 (0.83%)  0/61 (0.00%) 
Anorectal infection * 1  0/120 (0.00%)  1/61 (1.64%) 
Catheter related infection * 1  1/120 (0.83%)  0/61 (0.00%) 
Cecal infection * 1  1/120 (0.83%)  0/61 (0.00%) 
Enterocolitis infectious * 1  0/120 (0.00%)  1/61 (1.64%) 
Infections and infestations - Other, specify * 1  0/120 (0.00%)  1/61 (1.64%) 
Lung infection * 1  0/120 (0.00%)  1/61 (1.64%) 
Skin infection * 1  0/120 (0.00%)  1/61 (1.64%) 
Urinary tract infection * 1  0/120 (0.00%)  1/61 (1.64%) 
Infection of unknown source * 1  1/120 (0.83%)  0/61 (0.00%) 
Lung infection * 1  2/120 (1.67%)  0/61 (0.00%) 
Sepsis * 1  2/120 (1.67%)  0/61 (0.00%) 
Soft tissue infection * 1  2/120 (1.67%)  0/61 (0.00%) 
Upper respiratory infection * 1  1/120 (0.83%)  0/61 (0.00%) 
Injury, poisoning and procedural complications     
Fall * 1  2/120 (1.67%)  0/61 (0.00%) 
Intestinal stoma site bleeding * 1  1/120 (0.83%)  0/61 (0.00%) 
Stomal ulcer * 1  1/120 (0.83%)  0/61 (0.00%) 
Investigations     
Alanine aminotransferase increased * 1  1/120 (0.83%)  0/61 (0.00%) 
Alkaline phosphatase increased * 1  1/120 (0.83%)  0/61 (0.00%) 
Aspartate aminotransferase increased * 1  1/120 (0.83%)  0/61 (0.00%) 
Blood bilirubin increased * 1  1/120 (0.83%)  0/61 (0.00%) 
GGT increased * 1  1/120 (0.83%)  0/61 (0.00%) 
Obstructive Jaundice * 1  1/120 (0.83%)  0/61 (0.00%) 
Deteriorating LFT's * 1  1/120 (0.83%)  0/61 (0.00%) 
Elevated INR * 1  1/120 (0.83%)  0/61 (0.00%) 
Neutrophil count decreased * 1  6/120 (5.00%)  0/61 (0.00%) 
Platelet count decreased * 1  2/120 (1.67%)  0/61 (0.00%) 
Metabolism and nutrition disorders     
Anorexia * 1  3/120 (2.50%)  1/61 (1.64%) 
Dehydration * 1  5/120 (4.17%)  3/61 (4.92%) 
Hypoalbuminemia * 1  1/120 (0.83%)  0/61 (0.00%) 
severely elevated lipase level * 1  1/120 (0.83%)  0/61 (0.00%) 
Malnutrician * 1  1/120 (0.83%)  0/61 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  1/120 (0.83%)  0/61 (0.00%) 
Muscle weakness lower limb * 1  0/120 (0.00%)  1/61 (1.64%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumor pain * 1  1/120 (0.83%)  0/61 (0.00%) 
Nervous system disorders     
Headache * 1  1/120 (0.83%)  0/61 (0.00%) 
Movements involuntary * 1  0/120 (0.00%)  1/61 (1.64%) 
Syncope * 1  1/120 (0.83%)  0/61 (0.00%) 
Psychiatric disorders     
Insomnia * 1  1/120 (0.83%)  0/61 (0.00%) 
Psychosis * 1  1/120 (0.83%)  0/61 (0.00%) 
Renal and urinary disorders     
Acute kidney injury * 1  1/120 (0.83%)  0/61 (0.00%) 
Reproductive system and breast disorders     
Pelvic pain * 1  0/120 (0.00%)  1/61 (1.64%) 
Respiratory, thoracic and mediastinal disorders     
Aspiration * 1  0/120 (0.00%)  1/61 (1.64%) 
Cough * 1  1/120 (0.83%)  0/61 (0.00%) 
Dyspnea * 1  3/120 (2.50%)  1/61 (1.64%) 
Pneumonitis * 1  0/120 (0.00%)  1/61 (1.64%) 
Pleural effusion * 1  1/120 (0.83%)  0/61 (0.00%) 
Skin and subcutaneous tissue disorders     
Hyperhidrosis * 1  1/120 (0.83%)  0/61 (0.00%) 
Palmar-plantar erythrodysesthesia syndrome * 1  1/120 (0.83%)  0/61 (0.00%) 
right hip abscess * 1  1/120 (0.83%)  0/61 (0.00%) 
Surgical and medical procedures     
Surgical and medical procedures - Other, specify * 1  0/120 (0.00%)  1/61 (1.64%) 
Vascular disorders     
Hypertension * 1  1/120 (0.83%)  0/61 (0.00%) 
Thromboembolic event * 1  3/120 (2.50%)  2/61 (3.28%) 
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A Arm B
Affected / at Risk (%) Affected / at Risk (%)
Total   118/120 (98.33%)   61/61 (100.00%) 
Blood and lymphatic system disorders     
Anemia * 1  67/120 (55.83%)  38/61 (62.30%) 
Febrile neutropenia * 1  7/120 (5.83%)  1/61 (1.64%) 
Cardiac disorders     
Sinus tachycardia * 1  6/120 (5.00%)  2/61 (3.28%) 
Endocrine disorders     
Hypothyroidism * 1  8/120 (6.67%)  1/61 (1.64%) 
Gastrointestinal disorders     
Abdominal pain * 1  41/120 (34.17%)  9/61 (14.75%) 
Constipation * 1  41/120 (34.17%)  17/61 (27.87%) 
Diarrhea * 1  63/120 (52.50%)  28/61 (45.90%) 
Dysgeusia * 1  6/120 (5.00%)  2/61 (3.28%) 
Dyspepsia * 1  9/120 (7.50%)  1/61 (1.64%) 
Dysphagia * 1  6/120 (5.00%)  1/61 (1.64%) 
Hemorrhoids * 1  10/120 (8.33%)  2/61 (3.28%) 
Mucositis oral * 1  65/120 (54.17%)  20/61 (32.79%) 
Nausea * 1  60/120 (50.00%)  34/61 (55.74%) 
Oral pain * 1  8/120 (6.67%)  0/61 (0.00%) 
Rectal pain * 1  10/120 (8.33%)  1/61 (1.64%) 
Vomiting * 1  40/120 (33.33%)  10/61 (16.39%) 
General disorders     
Edema limbs * 1  5/120 (4.17%)  4/61 (6.56%) 
Fatigue * 1  76/120 (63.33%)  33/61 (54.10%) 
Fever * 1  18/120 (15.00%)  3/61 (4.92%) 
Flu like symptoms * 1  7/120 (5.83%)  1/61 (1.64%) 
Pain * 1  26/120 (21.67%)  4/61 (6.56%) 
Infections and infestations     
Urinary tract infection * 1  11/120 (9.17%)  3/61 (4.92%) 
Investigations     
Activated partial thromboplastin time prolonged * 1  7/120 (5.83%)  3/61 (4.92%) 
Alanine aminotransferase increased * 1  30/120 (25.00%)  9/61 (14.75%) 
Alkaline phosphatase increased * 1  35/120 (29.17%)  14/61 (22.95%) 
Aspartate aminotransferase increased * 1  28/120 (23.33%)  10/61 (16.39%) 
Blood bilirubin increased * 1  22/120 (18.33%)  4/61 (6.56%) 
Creatinine increased * 1  6/120 (5.00%)  5/61 (8.20%) 
INR increased * 1  6/120 (5.00%)  5/61 (8.20%) 
Lipase increased * 1  21/120 (17.50%)  13/61 (21.31%) 
Lymphocyte count decreased * 1  15/120 (12.50%)  11/61 (18.03%) 
Neutrophil count decreased * 1  69/120 (57.50%)  36/61 (59.02%) 
Platelet count decreased * 1  34/120 (28.33%)  9/61 (14.75%) 
Serum amylase increased * 1  16/120 (13.33%)  8/61 (13.11%) 
Weight loss * 1  27/120 (22.50%)  5/61 (8.20%) 
White blood cell decreased * 1  35/120 (29.17%)  23/61 (37.70%) 
Metabolism and nutrition disorders     
Anorexia * 1  43/120 (35.83%)  7/61 (11.48%) 
Dehydration * 1  15/120 (12.50%)  5/61 (8.20%) 
Hyperglycemia * 1  17/120 (14.17%)  16/61 (26.23%) 
Hypertriglyceridemia * 1  25/120 (20.83%)  19/61 (31.15%) 
Hypoalbuminemia * 1  37/120 (30.83%)  14/61 (22.95%) 
Hyperuricemia * 1  5/120 (4.17%)  7/61 (11.48%) 
Hypocalcemia * 1  29/120 (24.17%)  10/61 (16.39%) 
Hypokalemia * 1  40/120 (33.33%)  19/61 (31.15%) 
Hypomagnesemia * 1  16/120 (13.33%)  9/61 (14.75%) 
Hyponatremia * 1  20/120 (16.67%)  13/61 (21.31%) 
Hypophosphatemia * 1  38/120 (31.67%)  6/61 (9.84%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  12/120 (10.00%)  4/61 (6.56%) 
Bone pain * 1  6/120 (5.00%)  0/61 (0.00%) 
Pain in extremity * 1  8/120 (6.67%)  3/61 (4.92%) 
Nervous system disorders     
Dizziness * 1  9/120 (7.50%)  1/61 (1.64%) 
Headache * 1  24/120 (20.00%)  6/61 (9.84%) 
Peripheral sensory neuropathy * 1  28/120 (23.33%)  8/61 (13.11%) 
Psychiatric disorders     
Anxiety * 1  6/120 (5.00%)  1/61 (1.64%) 
Depression * 1  9/120 (7.50%)  5/61 (8.20%) 
Insomnia * 1  13/120 (10.83%)  3/61 (4.92%) 
Renal and urinary disorders     
Hematuria * 1  9/120 (7.50%)  3/61 (4.92%) 
Proteinuria * 1  18/120 (15.00%)  14/61 (22.95%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  15/120 (12.50%)  4/61 (6.56%) 
Dyspnea * 1  22/120 (18.33%)  7/61 (11.48%) 
Epistaxis * 1  9/120 (7.50%)  2/61 (3.28%) 
Hoarseness * 1  15/120 (12.50%)  0/61 (0.00%) 
Sore throat * 1  11/120 (9.17%)  1/61 (1.64%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  30/120 (25.00%)  15/61 (24.59%) 
Dry skin * 1  15/120 (12.50%)  5/61 (8.20%) 
Palmar-plantar erythrodysesthesia syndrome * 1  35/120 (29.17%)  6/61 (9.84%) 
Rash maculo-papular * 1  18/120 (15.00%)  5/61 (8.20%) 
Rash acneiform * 1  12/120 (10.00%)  2/61 (3.28%) 
Vascular disorders     
Hypertension * 1  23/120 (19.17%)  9/61 (14.75%) 
Hypotension * 1  10/120 (8.33%)  3/61 (4.92%) 
Thromboembolic event * 1  10/120 (8.33%)  1/61 (1.64%) 
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Robin V. Johnson
Organization: UNC Lineberger Comprehensive Cancer Center
Phone: 919-966-1125
EMail: Robin_V_Johnson@med.unc.edu
Layout table for additonal information
Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01298570     History of Changes
Other Study ID Numbers: LCCC 1029
10-2176 ( Other Identifier: UNC IRB )
First Submitted: February 16, 2011
First Posted: February 17, 2011
Results First Submitted: November 20, 2017
Results First Posted: February 28, 2018
Last Update Posted: July 4, 2019