Clinical Trial: Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma

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

Official Title: A Pilot Study to Evaluate Novel Agents (Temozolomide and Cixutumumab [IMC-A12, Anti-IGF-IR Monoclonal Antibody NSC # 742460]) in Combination With Intensive Multi-agent Interval Compressed Therapy for

Brief Summary: This randomized pilot clinical trial is studying the side effects and how well giving temozolomide and cixutumumab together with combination chemotherapy works in treating patients with metastatic rhabdomyosarcoma. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Giving temozolomide and cixutumumab together with combination chemotherapy may kill more tumor cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the feasibility of administering IMC-A12 (cixutumumab) in combination with a multi-agent intensive chemotherapy regimen for the treatment of high-risk rhabdomyosarcoma (RMS).

II. To determine the feasibility of adding temozolomide to vincristine (vincristine sulfate)/irinotecan (irinotecan hydrochloride) cycles in patients with high-risk RMS.

III. To assess immediate and short-term side effects of delivery of concurrent temozolomide-vincristine-irinotecan with irradiation in patients with high-risk RMS.

SECONDARY OBJECTIVES:

I. To gain a preliminary estimate of the response rate to IMC-A12 or temozolomide plus vincristine/irinotecan in previously untreated high-risk RMS.

II. To obtain preliminary efficacy data for IMC-A12 or temozolomide in combination with a multi-agent interval compressed chemotherapy regimen in previously untreated high-risk RMS.

III. To determine the effectiveness of detecting metastatic disease with fludeoxyglucose F 18 positron emission tomography (FDG PET) and to compare assessment of response using standard imaging techniques with response assessed by FDG PET.

IV. To assess changes in serum levels of insulin-like growth factor (IGF)-I, IGF-II, IGF-BP3 as biomarkers of IGF-IR inhibition.

OUTLINE: This is a dose-escalation study of cixutumumab. Patients are assigned to 1 of 2 treatment groups according to the timing of their enrollment onto the study.

GROUP 1: Patients rec
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Feasibility of the addition of cixutumumab to chemotherapy determined by patient enrollment [ Time Frame: Up to 54 weeks ]
  • Feasibility of the addition of temozolomide to chemotherapy determined by patient enrollment [ Time Frame: Up to 54 weeks ]
  • Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: 6 months ]


Original Primary Outcome:

  • Feasibility
  • Immediate and short-term side effects


Current Secondary Outcome:

  • Event-free survival [ Time Frame: Up to 5 years ]
  • Response rate assessed by Response Evaluation Criteria for Solid Tumors (RECIST) [ Time Frame: Up to 5 years ]
    An O'Brien-Fleming monitoring boundary (truncated at 3 standard deviations) and a spending function approach will be employed for interim monitoring of efficacy. A futility analysis will also be performed, testing a 'null hypothesis' that the relative risk of failure with this therapy is 0.60 (compared to the ID/IE therapy experience), with consideration of suspension of accrual should this hypothesis be rejected at any of the scheduled interim looks at a significance level of 0.005.


Original Secondary Outcome:

  • Preliminary response rate
  • Preliminary efficacy
  • Effectiveness of FDG PET in detecting metastatic disease
  • Levels of IGF-I, IGF-II, and IGF-BP3


Information By: National Cancer Institute (NCI)

Dates:
Date Received: January 22, 2010
Date Started: January 2010
Date Completion:
Last Updated: May 22, 2015
Last Verified: September 2014