Clinical Trial: IMC-A12 in Treating Young Patients With Relapsed or Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor or Other Solid Tumor

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

Official Title: A Phase I Study of IMC-A12 (Anti-IGF-I Receptor Monoclonal Antibody, NSC #742460) in Children With Relapsed/Refractory Solid Tumors

Brief Summary: This phase I clinical trial is studying the side effects and best dose of IMC-A12 in treating young patients with relapsed or refractory Ewing sarcoma/peripheral primitive neuroectodermal tumor or other solid tumors. Monoclonal antibodies, such as IMC-A12, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) or recommended phase II dose of IMC-A12 (cixutumumab) in children with relapsed or refractory solid tumors using a limited dose-escalation strategy.

II. To define and describe the toxicities of this drug in children with relapsed or refractory solid tumors.

III. To characterize the pharmacokinetics of this drug in children with relapsed or refractory solid tumors.

SECONDARY OBJECTIVES:

I. To preliminarily define the antitumor activity of this drug in children with relapsed or refractory solid tumors within the confines of a phase I study.

II. To obtain initial phase II efficacy data on the antitumor activity of this drug in children with Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET).

III. To examine change in IGF-IR and insulin receptor (IR) levels and IGF-IR and IR activation in lymphocytes as biomarkers of IMC-A12 action and specificity.

IV. To evaluate the effect of this drug on circulating levels of proteins involved in linear growth and glucose homeostasis, including IGF-I, IGF-II, IGF-BP3, growth hormone, insulin, and C-peptide.

V. To develop exploratory data concerning biomarkers of activity.

OUTLINE: This is a dose-escalation study.

Patients receive cixutumumab IV over 1 hour on days 1, 8, 15, and 22. Treatment repeats every 4 weeks for up to 2 years in the absence of unacceptable toxicity
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 [ Time Frame: Weekly during each course ]
    Toxicity tables will be constructed to summarize the observed incidence by severity and type of toxicity.
  • MTD or recommended phase II dose [ Time Frame: During course 1 ]
    MTD will be the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT). DLT is defined as any hematological and non-hematological toxicities that is possible, probably, or definitely attributed to IMC-A12.
  • Pharmacokinetics of IMC-A12 [ Time Frame: At baseline, days 1, 8, 15, 22, and 28 of course 1, and days 15 and 28 of course 2 ]


Original Primary Outcome:

  • Maximum tolerated dose or recommended phase II dose
  • Toxicity profile
  • Response rate (complete and partial)
  • Pharmacokinetics


Current Secondary Outcome: Response rate (complete or partial response) in patients with Ewing sarcoma/peripheral PNET [ Time Frame: Up to 30 days after completion of treatment ]

Confidence intervals will be constructed according to the method of Chang and O'Brien to account for the two-stage design.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: February 2, 2008
Date Started: January 2008
Date Completion:
Last Updated: June 18, 2014
Last Verified: June 2014