Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01614795
Recruitment Status : Completed
First Posted : June 8, 2012
Results First Posted : March 31, 2015
Last Update Posted : December 11, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Childhood Alveolar Soft Part Sarcoma
Childhood Angiosarcoma
Childhood Epithelioid Sarcoma
Childhood Fibrosarcoma
Childhood Gliosarcoma
Childhood Leiomyosarcoma
Childhood Liposarcoma
Childhood Malignant Peripheral Nerve Sheath Tumor
Childhood Synovial Sarcoma
Previously Treated Childhood Rhabdomyosarcoma
Recurrent Childhood Rhabdomyosarcoma
Recurrent Childhood Soft Tissue Sarcoma
Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
Recurrent Osteosarcoma
Rhabdomyosarcoma
Interventions Biological: Cixutumumab
Other: Laboratory Biomarker Analysis
Drug: Temsirolimus
Enrollment 46
Recruitment Details  
Pre-assignment Details The analysis strategy for secondary outcome measures accommodates the possibility that the Progression-Free Interval and IHC could have different statistical characteristics across the different histologies that define the study groups.
Arm/Group Title Group 1 Relapsed or Refractory Osteosarcoma Group 2 Relapsed or Refractory Ewing Sarcoma/Peripheral PNET Group 3 Relapsed or Refractory Rhabdomyosarcoma Group 4 Relapsed or Refractory Non-rhabdo Soft Tissue Sarcoma
Hide Arm/Group Description

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Period Title: Overall Study
Started 11 12 11 12
Completed 0 0 0 0
Not Completed 11 12 11 12
Reason Not Completed
Adverse Event             0             0             1             1
Lack of Efficacy             10             10             9             8
Physician Decision             1             0             1             1
Withdrawal by Subject             0             1             0             2
Ineligible             0             1             0             0
Arm/Group Title Group 1 Relapsed or Refractory Osteosarcoma Group 2 Relapsed or Refractory Ewing Sarcoma/Peripheral PNET Group 3 Relapsed or Refractory Rhabdomyosarcoma Group 4 Relapsed or Refractory Non-rhabdo Soft Tissue Sarcoma Total
Hide Arm/Group Description

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Total of all reporting groups
Overall Number of Baseline Participants 11 12 11 12 46
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 12 participants 11 participants 12 participants 46 participants
<=18 years
7
  63.6%
8
  66.7%
9
  81.8%
7
  58.3%
31
  67.4%
Between 18 and 65 years
4
  36.4%
4
  33.3%
2
  18.2%
5
  41.7%
15
  32.6%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 11 participants 12 participants 11 participants 12 participants 46 participants
18
(7 to 25)
17.5
(9 to 27)
14
(1 to 23)
17.5
(13 to 26)
17
(1 to 27)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 12 participants 11 participants 12 participants 46 participants
Female
1
   9.1%
6
  50.0%
8
  72.7%
5
  41.7%
20
  43.5%
Male
10
  90.9%
6
  50.0%
3
  27.3%
7
  58.3%
26
  56.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 12 participants 11 participants 12 participants 46 participants
Hispanic or Latino
1
   9.1%
0
   0.0%
3
  27.3%
0
   0.0%
4
   8.7%
Not Hispanic or Latino
10
  90.9%
12
 100.0%
8
  72.7%
11
  91.7%
41
  89.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
1
   2.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 12 participants 11 participants 12 participants 46 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   9.1%
1
   8.3%
0
   0.0%
2
  16.7%
4
   8.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
2
  16.7%
0
   0.0%
0
   0.0%
2
   4.3%
Black or African American
2
  18.2%
0
   0.0%
0
   0.0%
1
   8.3%
3
   6.5%
White
7
  63.6%
8
  66.7%
9
  81.8%
7
  58.3%
31
  67.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   9.1%
1
   8.3%
2
  18.2%
2
  16.7%
6
  13.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 11 participants 12 participants 11 participants 12 participants 46 participants
United States 11 11 11 12 45
Canada 0 1 0 0 1
1.Primary Outcome
Title Objective Response Rate (PR or CR) by Response Evaluation Criteria in Solid Tumors (RECIST).
Hide Description Per Response evaluation criteria In Solid Tumors Criteria (RECIST v1.0) 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. The combination of sufficient activity is considered if the true response rate is 35% or greater.
Time Frame 6 cycles (168 days)
Hide Outcome Measure Data
Hide Analysis Population Description
One (1) of the patients in Group 1 and one (1) of the patients in Group 4 were considered inevaluable for response assessment. One (1) of the patients in Group 2 was ineligible.
Arm/Group Title Group 1 Relapsed or Refractory Osteosarcoma Group 2 Relapsed or Refractory Ewing Sarcoma/Peripheral PNET Group 3 Relapsed or Refractory Rhabdomyosarcoma Group 4 Relapsed or Refractory Non-rhabdo Soft Tissue Sarcoma
Hide Arm/Group Description:

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 10 11 11 11
Measure Type: Number
Unit of Measure: participants
Non-Responder 10 11 11 11
Responder 0 0 0 0
2.Primary Outcome
Title Number of Cycles of Toxicity
Hide Description The number of patients-cycles where CTC Version 4 grade 3 or higher increased Alanine aminotransferase was observed
Time Frame Duration of protocol therapy - Up to 25 cycles (700 days)
Hide Outcome Measure Data
Hide Analysis Population Description
One hundred six (106) cycles were reported for the analysis of this toxicity
Arm/Group Title Treatment (Cixutumumab, Temsirolimus)
Hide Arm/Group Description:

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

Cixutumumab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Temsirolimus: Given IV

Overall Number of Participants Analyzed 46
Overall Number of Units Analyzed
Type of Units Analyzed: Cycles
106
Measure Type: Number
Unit of Measure: cycles
Alkaline phosphatase 1
Anaphylaxis 1
Anemia 3
Ascites 1
Aspartate aminotransferase 3
Decreased lymphocyte count 1
Decreased platelet count 5
Decreased white blood cells 3
Duodenal obstruction 1
Epistaxis 1
Extremity pain 1
Hyperglycemia 1
Hypermagnesemia 1
Hypertriglyceridemia 2
Hyperuricemia 1
Hypoalbuminemia 1
Hypokalemia 5
Hyponatremia 1
Hypophosphatemia 4
Hypoxia 1
Increased alanine aminotransferase 2
Increased blood bilirubin 1
Increased creatinine 1
Multi-organ failure 1
Neutopenia 6
Non-cardiac chest pain 1
Other cardiac disorders 1
Other infections and infestations 1
Oral mucocitis 4
Pain 2
Paronychia 1
Urinary tract infection 1
Urinary tract obstruction 1
Weight loss 1
Wound infection 1
3.Secondary Outcome
Title Progression-free Interval
Hide Description Percentage Probability of remaining progression-free 5 years after enrollment estimated by the method of Kaplan and Meier
Time Frame 10 months after enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
The 10 month time point was chosen since the shortest follow-up available was observed in Group 3 (relapsed or refractory rhabdomyosarcoma) where the last patient under observation was censored after completing 10 months of follow-up
Arm/Group Title Group 1 Relapsed or Refractory Osteosarcoma Group 2 Relapsed or Refractory Ewing Sarcoma/Peripheral PNET Group 3 Relapsed or Refractory Rhabdomyosarcoma Group 4 Relapsed or Refractory Non-rhabdo Soft Tissue Sarcoma
Hide Arm/Group Description:

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 10 11 11 11
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent probability
9.09
(0.54 to 33.29)
9.09
(0.54 to 33.29)
9.09
(0.54 to 33.29)
16.67
(2.65 to 41.30)
4.Secondary Outcome
Title Expression Levels of IGF-1R, Insulin Receptor, ERK, RON, and mTOR
Hide Description Number of patients expressing insulin-like growth factor 1 receptor (IGF-1R), insulin receptor, ERK, RON, and mammalian target of rapamycin (mTOR) at levels 0, 1+, 2+, 3+ by immunohistochemistry.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
All specimens for the IHC analysis for IGF-1R, Insulin Receptor, ERK, RON, and mTOR were obtained prior to the start of treatment on ADVL1221. Levels 0, 1+, 2+ and 3+ represent increasing strengths of IHC staining.
Arm/Group Title Group 1 Relapsed or Refractory Osteosarcoma Group 2 Relapsed or Refractory Ewing Sarcoma/Peripheral PNET Group 3 Relapsed or Refractory Rhabdomyosarcoma Group 4 Relapsed or Refractory Non-rhabdo Soft Tissue Sarcoma
Hide Arm/Group Description:

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 10 11 11 11
Measure Type: Count of Participants
Unit of Measure: Participants
IGF-1R level 0 Number Analyzed 10 participants 11 participants 11 participants 11 participants
2
  20.0%
4
  36.4%
1
   9.1%
3
  27.3%
IGF-1R level 1+ Number Analyzed 10 participants 11 participants 11 participants 11 participants
4
  40.0%
3
  27.3%
0
   0.0%
4
  36.4%
IGF-1R level 2+ Number Analyzed 10 participants 11 participants 11 participants 11 participants
2
  20.0%
2
  18.2%
2
  18.2%
5
  45.5%
IGF-1R level 3+ Number Analyzed 10 participants 11 participants 11 participants 11 participants
2
  20.0%
2
  18.2%
8
  72.7%
1
   9.1%
Insulin receptor level 0 Number Analyzed 9 participants 11 participants 11 participants 11 participants
4
  44.4%
4
  36.4%
4
  36.4%
3
  27.3%
Insulin receptor level 1+ Number Analyzed 9 participants 11 participants 11 participants 11 participants
2
  22.2%
2
  18.2%
1
   9.1%
2
  18.2%
Insulin receptor level 2+ Number Analyzed 9 participants 11 participants 11 participants 11 participants
2
  22.2%
3
  27.3%
4
  36.4%
2
  18.2%
Insulin receptor level 3+ Number Analyzed 9 participants 11 participants 11 participants 11 participants
1
  11.1%
2
  18.2%
2
  18.2%
2
  18.2%
ERK level 0 Number Analyzed 10 participants 11 participants 11 participants 11 participants
2
  20.0%
5
  45.5%
6
  54.5%
3
  27.3%
ERK level 1+ Number Analyzed 10 participants 11 participants 11 participants 11 participants
5
  50.0%
5
  45.5%
2
  18.2%
4
  36.4%
ERK level 2+ Number Analyzed 10 participants 11 participants 11 participants 11 participants
1
  10.0%
0
   0.0%
3
  27.3%
3
  27.3%
ERK Level 3+ Number Analyzed 10 participants 11 participants 11 participants 11 participants
2
  20.0%
1
   9.1%
0
   0.0%
1
   9.1%
RON level 0 Number Analyzed 10 participants 11 participants 11 participants 11 participants
7
  70.0%
10
  90.9%
10
  90.9%
6
  54.5%
RON level 1+ Number Analyzed 10 participants 11 participants 11 participants 11 participants
3
  30.0%
1
   9.1%
1
   9.1%
4
  36.4%
RON level 2+ Number Analyzed 10 participants 11 participants 11 participants 11 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
RON level 3+ Number Analyzed 10 participants 11 participants 11 participants 11 participants
0
   0.0%
0
   0.0%
0
   0.0%
1
   9.1%
mTOR level 0 Number Analyzed 10 participants 11 participants 11 participants 11 participants
8
  80.0%
7
  63.6%
10
  90.9%
8
  72.7%
mTOR level 1+ Number Analyzed 10 participants 11 participants 11 participants 11 participants
2
  20.0%
3
  27.3%
1
   9.1%
3
  27.3%
mTOR level 2+ Number Analyzed 10 participants 11 participants 11 participants 11 participants
0
   0.0%
1
   9.1%
0
   0.0%
0
   0.0%
mTOR level 3+ Number Analyzed 10 participants 11 participants 11 participants 11 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
5.Secondary Outcome
Title Number of Patients With Detectable Bone Marrow Micrometastatic Disease Estimated as the Proportion of Eligible Patients Entered Into the Ewing Sarcoma Stratum Who Have Detectable Tumor Cells in the Marrow at Enrollment
Hide Description [Not Specified]
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
2 patients of the 12 patients enrolled in the Ewing Sarcoma stratum submitted specimens for analysis
Arm/Group Title Treatment (Cixutumumab, Temsirolimus)
Hide Arm/Group Description:

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

Cixutumumab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Temsirolimus: Given IV

Overall Number of Participants Analyzed 2
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
Time Frame [Not Specified]
Adverse Event Reporting Description SAE field contains NCI Common Toxicity Criteria for Adverse Events (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 1 Relapsed or Refractory Osteosarcoma Group 2 Relapsed or Refractory Ewing Sarcoma/Peripheral PNET Group 3 Relapsed or Refractory Rhabdomyosarcoma Group 4 Relapsed or Refractory Non-rhabdo Soft Tissue Sarcoma
Hide Arm/Group Description

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

cixutumumab: Given IV, Days 1, 8, 15, and 22, dosage 6 mg/kg. Cixutumumab dose is based on weight (kg).

temsirolimus: Given IV, Days 1, 8, 15, and 22 8 mg/m2 (maximum dose = 16 mg) (Cycle 1), Dose escalation to 10 mg/m2 (maximum dose = 20 mg). Temsirolimus dose is based on BSA.

laboratory biomarker analysis: Correlative studies

All-Cause Mortality
Group 1 Relapsed or Refractory Osteosarcoma Group 2 Relapsed or Refractory Ewing Sarcoma/Peripheral PNET Group 3 Relapsed or Refractory Rhabdomyosarcoma Group 4 Relapsed or Refractory Non-rhabdo Soft Tissue Sarcoma
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Group 1 Relapsed or Refractory Osteosarcoma Group 2 Relapsed or Refractory Ewing Sarcoma/Peripheral PNET Group 3 Relapsed or Refractory Rhabdomyosarcoma Group 4 Relapsed or Refractory Non-rhabdo Soft Tissue Sarcoma
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/11 (18.18%)   3/11 (27.27%)   2/11 (18.18%)   7/12 (58.33%) 
Cardiac disorders         
Cardiac disorders - Other  0/11 (0.00%)  0/11 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Gastrointestinal disorders         
Ascites  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Duodenal obstruction  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Mucositis oral  0/11 (0.00%)  0/11 (0.00%)  0/11 (0.00%)  2/12 (16.67%) 
General disorders         
Fever  0/11 (0.00%)  0/11 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Multi-organ failure  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Non-cardiac chest pain  0/11 (0.00%)  1/11 (9.09%)  0/11 (0.00%)  0/12 (0.00%) 
Pain  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Immune system disorders         
Anaphylaxis  0/11 (0.00%)  0/11 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Infections and infestations         
Infections and infestations - Other  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Urinary tract infection  0/11 (0.00%)  0/11 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Wound infection  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Investigations         
Alanine aminotransferase increased  0/11 (0.00%)  0/11 (0.00%)  2/11 (18.18%)  0/12 (0.00%) 
Alkaline phosphatase increased  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Aspartate aminotransferase increased  0/11 (0.00%)  0/11 (0.00%)  2/11 (18.18%)  1/12 (8.33%) 
Blood bilirubin increased  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Creatinine increased  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Neutrophil count decreased  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Platelet count decreased  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Weight loss  1/11 (9.09%)  0/11 (0.00%)  0/11 (0.00%)  0/12 (0.00%) 
White blood cell decreased  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Metabolism and nutrition disorders         
Hypermagnesemia  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Hypertriglyceridemia  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  1/12 (8.33%) 
Hyperuricemia  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Hypoalbuminemia  0/11 (0.00%)  0/11 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Hypokalemia  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Hypophosphatemia  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  1/12 (8.33%) 
Musculoskeletal and connective tissue disorders         
Pain in extremity  0/11 (0.00%)  1/11 (9.09%)  0/11 (0.00%)  0/12 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other  2/11 (18.18%)  1/11 (9.09%)  0/11 (0.00%)  0/12 (0.00%) 
Renal and urinary disorders         
Urinary tract obstruction  0/11 (0.00%)  0/11 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Group 1 Relapsed or Refractory Osteosarcoma Group 2 Relapsed or Refractory Ewing Sarcoma/Peripheral PNET Group 3 Relapsed or Refractory Rhabdomyosarcoma Group 4 Relapsed or Refractory Non-rhabdo Soft Tissue Sarcoma
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/11 (100.00%)   5/11 (45.45%)   7/11 (63.64%)   6/12 (50.00%) 
Blood and lymphatic system disorders         
Anemia  2/11 (18.18%)  0/11 (0.00%)  2/11 (18.18%)  0/12 (0.00%) 
Gastrointestinal disorders         
Mucositis oral  5/11 (45.45%)  1/11 (9.09%)  3/11 (27.27%)  3/12 (25.00%) 
General disorders         
Pain  0/11 (0.00%)  0/11 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Infections and infestations         
Paronychia  0/11 (0.00%)  1/11 (9.09%)  0/11 (0.00%)  0/12 (0.00%) 
Investigations         
Creatinine increased  1/11 (9.09%)  0/11 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Lymphocyte count decreased  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Neutrophil count decreased  3/11 (27.27%)  0/11 (0.00%)  1/11 (9.09%)  1/12 (8.33%) 
Platelet count decreased  0/11 (0.00%)  2/11 (18.18%)  3/11 (27.27%)  0/12 (0.00%) 
White blood cell decreased  2/11 (18.18%)  0/11 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Metabolism and nutrition disorders         
Hyperglycemia  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Hypokalemia  3/11 (27.27%)  0/11 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Hyponatremia  2/11 (18.18%)  0/11 (0.00%)  0/11 (0.00%)  0/12 (0.00%) 
Hypophosphatemia  2/11 (18.18%)  0/11 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Nervous system disorders         
Tremor  0/11 (0.00%)  1/11 (9.09%)  0/11 (0.00%)  0/12 (0.00%) 
Psychiatric disorders         
Confusion  0/11 (0.00%)  1/11 (9.09%)  0/11 (0.00%)  0/12 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Epistaxis  0/11 (0.00%)  0/11 (0.00%)  1/11 (9.09%)  0/12 (0.00%) 
Hypoxia  0/11 (0.00%)  0/11 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
Vascular disorders         
Hypertension  0/11 (0.00%)  0/11 (0.00%)  0/11 (0.00%)  1/12 (8.33%) 
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.
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: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01614795    
Other Study ID Numbers: NCI-2012-01971
NCI-2012-01971 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ADVL1221
COG-ADVL1221
CDR0000734871
ADVL1221 ( Other Identifier: Childrens Oncology Group )
ADVL1221 ( Other Identifier: CTEP )
U10CA098543 ( U.S. NIH Grant/Contract )
First Submitted: June 6, 2012
First Posted: June 8, 2012
Results First Submitted: March 19, 2015
Results First Posted: March 31, 2015
Last Update Posted: December 11, 2018