Cixutumumab and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma
This phase I trial is studying the side effects and best dose of cixutumumab given together with doxorubicin hydrochloride and to see how well they work in treating patients with unresectable, locally advanced, or metastatic soft tissue sarcoma. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving monoclonal antibody cixutumumab together with doxorubicin hydrochloride may kill more tumor cells.
Adult Desmoplastic Small Round Cell Tumor
Adult Epithelioid Sarcoma
Adult Extraskeletal Chondrosarcoma
Adult Extraskeletal Osteosarcoma
Adult Malignant Fibrous Histiocytoma of Bone
Adult Malignant Hemangiopericytoma
Adult Malignant Mesenchymoma
Adult Synovial Sarcoma
Childhood Desmoplastic Small Round Cell Tumor
Childhood Epithelioid Sarcoma
Childhood Malignant Hemangiopericytoma
Childhood Malignant Mesenchymoma
Childhood Synovial Sarcoma
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
Drug: doxorubicin hydrochloride
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 Study of Doxorubicin and A12 in Advanced Soft Tissue Sarcoma|
- 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 [ Time Frame: Up to 2 courses of treatment ] [ Designated as safety issue: Yes ]The MTD is defined as the dose of Cixitumumab that induces dose-limiting toxicity (DLT) in no more than 20% of patients.
- Progression-free survival [ Time Frame: Until documented disease progression or death or loss-to-follow-up, assessed up to 6 months ] [ Designated as safety issue: No ]Will be estimated using the product-limit method Kaplan and Meier. With point-wise estimates for the 3 and 6-month progression-free survival proportions reported with 95% confidence intervals using Greenwood's formula for calculation of the variance.
- Overall survival [ Time Frame: Until death due to any cause, or loss to follow-up, assessed up to 6 months ] [ Designated as safety issue: No ]Will be estimated using the product-limit method Kaplan and Meier. With point-wise estimates for the 3 and 6-month survival proportions reported with 95% confidence intervals using Greenwood's formula for calculation of the variance.
- Changes in cardiac function as measured by MUGA scans of the left ventricular ejection fraction [ Time Frame: Baseline to 6 courses of treatment ] [ Designated as safety issue: No ]
- Confirmed response rate (CR + PR) for comparison with doxorubicin treatment in similar historical patient populations [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]The mean response probability with 90% credible interval will be reported for those patients treated at the dose of cixitumumab found to be the MTD.
|Study Start Date:||June 2008|
|Primary Completion Date:||January 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (cixutumumab and doxorubicin hydrochloride)
Patients receive cixutumumab 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.
Other Names:Drug: doxorubicin hydrochloride
Other Names:Other: laboratory biomarker analysis
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00720174
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|Decatur Memorial Hospital|
|Decatur, Illinois, United States, 62526|
|NorthShore University HealthSystem-Evanston Hospital|
|Evanston, Illinois, United States, 60201|
|Ingalls Memorial Hospital|
|Harvey, Illinois, United States, 60426|
|Joliet Oncology-Hematology Associates Limited|
|Joliet, Illinois, United States, 60435|
|Loyola University Medical Center|
|Maywood, Illinois, United States, 60153|
|Peoria, Illinois, United States, 61615|
|Central Illinois Hematology Oncology Center|
|Springfield, Illinois, United States, 60702|
|United States, Indiana|
|Fort Wayne Medical Oncology and Hematology Inc-Parkview|
|Fort Wayne, Indiana, United States, 46845|
|United States, Maryland|
|University of Maryland/Greenebaum Cancer Center|
|Baltimore, Maryland, United States, 21201|
|United States, Michigan|
|University of Michigan University Hospital|
|Ann Arbor, Michigan, United States, 48109|
|University of Michigan|
|Ann Arbor, Michigan, United States, 48109|
|United States, Missouri|
|Saint John's Mercy Medical Center|
|Saint Louis, Missouri, United States, 63141|
|United States, Wisconsin|
|Froedtert and the Medical College of Wisconsin|
|Milwaukee, Wisconsin, United States, 53226|
|Principal Investigator:||Rashmi Chugh||University of Chicago|