Clinical Trial: Cixutumumab and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 1 Study of Doxorubicin and A12 in Advanced Soft Tissue Sarcoma

Brief Summary: 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.

Detailed Summary:

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.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: 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 ]

The MTD is defined as the dose of Cixitumumab that induces dose-limiting toxicity (DLT) in no more than 20% of patients.


Original Primary Outcome:

  • Maximum tolerated dose of anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • Confirmed response rate (complete and partial response as defined by RECIST) of anti-IGF-1R recombinant monoclonal antibody IMC-A12 in combination with doxorubicin hydrochloride


Current Secondary Outcome:

  • Changes in cardiac function as measured by MUGA scans of the left ventricular ejection fraction [ Time Frame: Baseline to 6 courses of treatment ]
  • Confirmed response rate (CR + PR) for comparison with doxorubicin treatment in similar historical patient populations [ Time Frame: Up to 6 months ]
    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.
  • Overall survival [ Time Frame: Until death due to any cause, or loss to follow-up, assessed up to 6 months ]
    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.
  • Progression-free survival [ Time Frame: Until documented disease progression or death or loss-to-follow-up, assessed up to 6 months ]
    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.


Original Secondary Outcome:

  • Progression-free and overall survival at 3 and 6 months
  • Changes in left ventricular ejection fraction levels from baseline as measured by MUGA scans after 2, 4, and 6 courses of combination therapy


Information By: National Cancer Institute (NCI)

Dates:
Date Received: July 19, 2008
Date Started: June 2008
Date Completion:
Last Updated: May 16, 2016
Last Verified: May 2016