A Phase 1 Study of Doxorubicin and A12 in Advanced Soft Tissue Sarcoma
16 Years
N/A
Both
Adult Angiosarcoma, Adult Desmoplastic Small Round Cell Tumor, Adult Epithelioid Sarcoma, Adult Extraskeletal Chondrosarcoma, Adult Extraskeletal Osteosarcoma, Adult Fibrosarcoma, Adult Leiomyosarcoma, Adult Liposarcoma, Adult Malignant Fibrous Histiocytoma of Bone, Adult Malignant Hemangiopericytoma, Adult Malignant Mesenchymoma, Adult Neurofibrosarcoma, Adult Rhabdomyosarcoma, Adult Synovial Sarcoma, Childhood Angiosarcoma, Childhood Desmoplastic Small Round Cell Tumor, Childhood Epithelioid Sarcoma, Childhood Fibrosarcoma, Childhood Leiomyosarcoma, Childhood Liposarcoma, Childhood Malignant Hemangiopericytoma, Childhood Malignant Mesenchymoma, Childhood Neurofibrosarcoma, Childhood Synovial Sarcoma, Dermatofibrosarcoma Protuberans, Metastatic Childhood Soft Tissue Sarcoma, Mixed Childhood Rhabdomyosarcoma, Pleomorphic Childhood Rhabdomyosarcoma, Previously Treated Childhood Rhabdomyosarcoma, Previously Untreated Childhood Rhabdomyosarcoma, Recurrent Adult Soft Tissue Sarcoma, Recurrent Childhood Rhabdomyosarcoma, Recurrent Childhood Soft Tissue Sarcoma, Stage III Adult Soft Tissue Sarcoma, Stage IV Adult Soft Tissue Sarcoma
Trial Information
A Phase 1 Study of Doxorubicin and A12 in Advanced Soft Tissue Sarcoma
PRIMARY OBJECTIVES:
I. To collect safety data about the combination of doxorubicin and Cixitumumab and determine
if they can be combined with acceptable toxicity at full doses.
SECONDARY OBJECTIVES:
I. To assess the confirmed response rate (CR + PR as defined by RECIST) of patients with
locally advanced or metastatic soft tissue sarcoma when treated with combination doxorubicin
and Cixitumumab II. To assess the 3 and 6 month progression free survival rate of patients
treated with doxorubicin and Cixitumumab.
III. To assess the progression free survival and overall survival of patients treated with
doxorubicin and Cixitumumab.
IV. To evaluate changes in left ventricular ejection fraction assessed by MUGA scan after 2,
4 and 6 cycles of therapy compared to baseline.
OUTLINE: This is a multicenter, dose-escalation study of anti-IGF-1R recombinant monoclonal
antibody cixutumumab.
Patients receive cixutumumab intravenously (IV) over 1 hour on days 1, 8, and 15 and
doxorubicin hydrochloride IV continuously over 44-52 hours beginning on day 1. Treatment
repeats every 21 days for up to 6 courses in the absence of disease progression or
unacceptable toxicity. Patients with stable or responding disease may continue to receive
cixutumumab in the absence of disease progression or unacceptable toxicity.
Inclusion Criteria:
- Histologically or cytologically confirmed soft tissue sarcoma
- Unresectable disease
- Locally advanced or metastatic disease
- The following tumor types are not allowed:
- Embryonal and alveolar rhabdomyosarcoma
- Gastrointestinal stromal tumor
- Alveolar soft part sarcoma
- Clear cell sarcoma
- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques or ≥ 10 mm by spiral CT scan
- No more than 1 prior therapy for sarcoma
- No known brain metastases
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- ANC ≥ 1,500/µL
- Platelet count ≥ 100,000/µL
- Leukocytes ≥ 3,000/µL
- Total bilirubin ≤ upper limit of normal(ULN)
- AST and ALT ≤ 2.5 times ULN
- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
- Fasting serum glucose < 120 mg/dL OR below ULN
- LVEF ≥ 50% by MUGA scan
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after the
last dose of anti-IGF-1R recombinant monoclonal antibody IMC-A12
- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to anti-IGF-1R recombinant monoclonal antibody IMC-A12
- No poorly controlled diabetes mellitus
- Patients with a history of diabetes mellitus are eligible provided their blood
glucose is within normal range and they are on a stable dietary or therapeutic
regimen for this condition
- No concurrent uncontrolled illness including, but not limited to, any of the
following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situation that would preclude compliance with
study requirements
- No other concurrent investigational or commercial agents or therapies
- Recovered from all prior therapy
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
- More than 4 weeks since prior major surgery, hormonal therapy (other than
replacement), or hormonal therapy
- No prior radiotherapy to the heart, mediastinum, or chest wall
- No prior anthracycline therapy or anti-IGF-1R therapy
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximally tolerated dose (MTD) of cixitumumab when administered in a combination regimen with fixed dose doxorubicin hydrochloride, in patients with locally advanced or metastatic soft tissue sarcoma
Outcome Description:
The MTD is defined as the dose of Cixitumumab that induces dose-limiting toxicity (DLT) in no more than 20% of patients.
Outcome Time Frame:
Up to 2 courses of treatment
Safety Issue:
Yes
Principal Investigator
Rashmi Chugh
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Chicago Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00285
NCT ID:
NCT00720174
Start Date:
June 2008
Completion Date:
Related Keywords:
- Adult Angiosarcoma
- Adult Desmoplastic Small Round Cell Tumor
- Adult Epithelioid Sarcoma
- Adult Extraskeletal Chondrosarcoma
- Adult Extraskeletal Osteosarcoma
- Adult Fibrosarcoma
- Adult Leiomyosarcoma
- Adult Liposarcoma
- Adult Malignant Fibrous Histiocytoma of Bone
- Adult Malignant Hemangiopericytoma
- Adult Malignant Mesenchymoma
- Adult Neurofibrosarcoma
- Adult Rhabdomyosarcoma
- Adult Synovial Sarcoma
- Childhood Angiosarcoma
- Childhood Desmoplastic Small Round Cell Tumor
- Childhood Epithelioid Sarcoma
- Childhood Fibrosarcoma
- Childhood Leiomyosarcoma
- Childhood Liposarcoma
- Childhood Malignant Hemangiopericytoma
- Childhood Malignant Mesenchymoma
- Childhood Neurofibrosarcoma
- Childhood Synovial Sarcoma
- Dermatofibrosarcoma Protuberans
- Metastatic Childhood Soft Tissue Sarcoma
- Mixed Childhood Rhabdomyosarcoma
- Pleomorphic Childhood Rhabdomyosarcoma
- Previously Treated Childhood Rhabdomyosarcoma
- Previously Untreated Childhood Rhabdomyosarcoma
- Recurrent Adult Soft Tissue Sarcoma
- Recurrent Childhood Rhabdomyosarcoma
- Recurrent Childhood Soft Tissue Sarcoma
- Stage III Adult Soft Tissue Sarcoma
- Stage IV Adult Soft Tissue Sarcoma
- Histiocytoma
- Chondrosarcoma
- Fibrosarcoma
- Hemangiopericytoma
- Hemangiosarcoma
- Leiomyosarcoma
- Liposarcoma
- Mesenchymoma
- Osteosarcoma
- Rhabdomyosarcoma
- Sarcoma, Synovial
- Sarcoma
- Histiocytoma, Benign Fibrous
- Dermatofibrosarcoma
- Neurofibrosarcoma
- Neurilemmoma
- Rhabdomyosarcoma, Embryonal
- Desmoplastic Small Round Cell Tumor
- Histiocytoma, Malignant Fibrous
- Liver Neoplasms
Name | Location |
|---|---|
| Loyola University Medical Center | Maywood, Illinois 60153 |
| Ingalls Memorial Hospital | Harvey, Illinois 60426 |
| Central Illinois Hematology Oncology Center | Springfield, Illinois 62701 |
| Decatur Memorial Hospital | Decatur, Illinois 62526 |
| University of Chicago Comprehensive Cancer Center | Chicago, Illinois 60637-1470 |
| Froedtert and the Medical College of Wisconsin | Milwaukee, Wisconsin 53226 |
| Evanston CCOP-NorthShore University HealthSystem | Evanston, Illinois 60201 |
| Joliet Oncology-Hematology Associates Limited | Joliet, Illinois 60435 |
| Illinois CancerCare-Peoria | Peoria, Illinois 61615 |
| Fort Wayne Medical Oncology and Hematology Inc - State Boulevard | Fort Wayne, Indiana 46845 |
| Saint John's Mercy Medical Center | Saint Louis, Missouri 63141 |
| University of Maryland Greenebaum Cancer Center | Baltimore, Maryland 21201 |
| University of Michigan University Hospital | Ann Arbor, Michigan 48109 |
