Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma
Summary
RATIONALE: 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.
PURPOSE: This 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.
Description
OBJECTIVES:
Primary
- To determine the feasibility of administering cixutumumab in combination with an intensive multi-agent interval compressed chemotherapy regimen for the treatment of high-risk metastatic rhabdomyosarcoma (RMS).
- To determine the feasibility of adding temozolomide to vincristine and irinotecan in these patients.
- To assess immediate and short-term side effects of concurrent temozolomide, vincristine, and irinotecan with radiotherapy in these patients.
- To determine the feasibility of administering cixutumumab in combination with an intensive multi-agent interval compressed chemotherapy regimen comprising temozolomide, vincristine, and irinotecan in these patients.
Secondary
- To gain a preliminary estimate of the response rate to cixutumumab and/or temozolomide, vincristine, and irinotecan in these patients.
- To obtain preliminary efficacy data for cixutumumab and/or temozolomide in combination with an intensive multi-agent interval compressed chemotherapy regimen in these patients.
- 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.
- To assess changes in serum levels of IGF-I, IGF-II, IGF-BP3 as biomarkers of IGF-IR inhibition.
OUTLINE: This is a multicenter, dose-escalation study of cixutumumab. Patients are assigned to 1 of 3 treatment groups according to the timing of their enrollment onto the study.
- Group 1: Patients receive vincristine sulfate IV on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, and 30; doxorubicin hydrochloride IV on days 1 and 2 of weeks 7, 11, 15, 28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; dactinomycin IV on day 1 of weeks 35, 38, 41, and 44; and cixutumumab IV over 1 hour on day 1 of weeks 1-51. Patients also undergo radiotherapy* on days 1-5 of weeks 20-24.
- Group 2: Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo radiotherapy* as in group 1. Patients also receive oral temozolomide on days 1-5 of weeks 1, 4, 20, 23, 47, and 50.
- Group 3: Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, dactinomycin, and cixutumumab and undergo radiotherapy* as in group 1. Patients also receive temozolomide as in group 2.
- NOTE: *Patients with parameningeal tumors and evidence of intracranial extension or those requiring emergency radiotherapy may receive radiotherapy starting in week 1; cixutumumab should be withheld during radiotherapy.
Patients in groups 1 and 3 may undergo blood sample collection at baseline and after completion of week 6 for IGF-I, IGF-II, and IGF-BP3 biomarker analysis.
After completion of study therapy, patients are followed up periodically for up to 10 years.
Study Design
Masking: Open Label, Primary Purpose: Treatment
Conditions
Sarcoma
Intervention
cixutumumab, dactinomycin, cyclophosphamide, doxorubicin hydrochloride, etoposide, ifosfamide, irinotecan hydrochloride, temozolomide, vincristine sulfate
Location
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock
Arkansas
United States
72205
Status
Recruiting
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01055314
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-08-27T03:16:26-0400
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Medical and Biotech [MESH] Definitions
Mesna
A sulfhydryl compound used to prevent urothelial toxicity by inactivating metabolites from ANTINEOPLASTIC AGENTS, such as IFOSFAMIDE or CYCLOPHOSPHAMIDE.
Ifosfamide
Positional isomer of CYCLOPHOSPHAMIDE which is active as an alkylating agent and an immunosuppressive agent.
Etoposide
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
Cytochrome P-450 Cyp2b1
A major cytochrome P-450 enzyme which is inducible by PHENOBARBITAL in both the LIVER and SMALL INTESTINE. It is active in the metabolism of compounds like pentoxyresorufin, TESTOSTERONE, and ANDROSTENEDIONE. This enzyme, encoded by CYP2B1 gene, also mediates the activation of CYCLOPHOSPHAMIDE and IFOSFAMIDE to MUTAGENS.
Dactinomycin
A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015)
