Clinical Trial: Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase II Study of Cixutumumab (IMC-A12) in Combination With Temsirolimus in Pediatric Patients With Recurrent or Refractory Solid Tumors

Brief Summary: This phase II trial studies how well cixutumumab and temsirolimus work in treating patients with recurrent or refractory 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. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cixutumumab and temsirolimus together may kill more tumor cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the objective response rate to the combination of cixutumumab and temsirolimus in patients with relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, or non-rhabdomyosarcoma soft tissue sarcoma.

SECONDARY OBJECTIVES:

I. To assess the progression-free survival for patients treated in each disease stratum with this drug combination.

II. To assess the incidence of insulin-like growth factor 1 receptor (IGF-1R), insulin receptor, ERK, RON, and mammalian target of rapamycin (mTOR) pathway activation in archival tumor material, and correlate with response.

III. To evaluate minimal residual disease and IGF-1R tumor cell expression in the blood and bone marrow of Ewing sarcoma patients using flow cytometry.

IV. To further describe the toxicities (including dose-limiting toxicities) of cixutumumab and temsirolimus administered on this schedule.

OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis (osteosarcoma vs Ewing sarcoma/PNET vs rhabdomyosarcoma vs non-rhabdomyosarcoma soft tissue sarcoma).

Patients receive cixutumumab IV over 1 hour and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

Archived tumor tissue samples from most recent biopsy are collected and analyzed for IGF-1R, insulin receptor, AKT, ERK, mTOR, and S6 kinase pathway activation by immunohistochemistry (IHC) and
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Objective Response Rate (PR or CR) by Response Evaluation Criteria in Solid Tumors (RECIST). [ Time Frame: 6 cycles (168 days) ]

We will consider the combination of sufficient activity if the true response rate is 35% or greater. .


Original Primary Outcome:

  • Objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST), assessed up to 5 years
  • Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0


Current Secondary Outcome:

  • Progression-free Survival [ Time Frame: The date of enrollment until the end PFI date, calculated as the date of disease progression, date of death, date of removal of all tumor by surgery or last patient contact, whichever occurs first, assessed up to 5 years ]
    Will be calculated according to the method of Gray accounting for censoring and the competing events.
  • Percentage of Patients Expressing IGF-1R, Insulin Receptor, ERK, RON, and mTOR [ Time Frame: Up to 5 years ]
  • Percentage of Patients With Detectable Bone Marrow Micrometastatic Disease Estimated as the Proportion of Eligible Patients Entered Into the Ewing Sarcoma Stratum Who Have Detectable Tumor Cells in the Marrow at Enrollment [ Time Frame: Baseline ]
  • Observed Incidence in Each Reporting Period by Type and Grade of Toxicity as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [ Time Frame: 25 cycles (700 days) ]


Original Secondary Outcome:

  • Progression-free survival assessed up to 5 years
  • Expression of IGF-1R, insulin receptor, ERK, RON, and mTOR
  • Percentage of patients with detectable bone marrow micrometastatic disease at baseline estimated as the proportion of eligible patients entered into the Ewing sarcoma stratum who have detectable tumor cells in the marrow at enrollment


Information By: National Cancer Institute (NCI)

Dates:
Date Received: June 6, 2012
Date Started: June 2012
Date Completion:
Last Updated: November 1, 2016
Last Verified: November 2016