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Pediatric Cancers

Phase I Study of Temsirolimus in Combination With Irinotecan and Temozolomide in Children, Adolescents, and Young Adults With Relapsed or Refractory Solid Tumors

NCI-11-C-0053, NCT01141244

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Investigator(s):

Brigitte Widemann, M.D.
Principal Investigator
Phone: 301-496-7387
widemanb@mail.nih.gov

Referral Contact(s):

Pediatric Oncology
Phone: 301-496-4256
1-877-624-4878 (Toll free)

 

Background:

  • When activated and associated with appropriate members of a functional complex, the mammalian target of rapamycin (mTOR) plays an important role in regulation of protein synthesis, cell growth, and proliferation
  • mTOR inhibitors have the potential to augment the activity of conventional chemotherapeutic drugs
  • Irinotecan and temozolomide in combination have activity against solid tumors such as Ewing sarcoma and neuroblastoma and are associated with relatively mild toxicity
  • In this Phase 1 study, mTOR inhibitor temsirolimus will be administered in combination with irinotecan and temozolomide in patients with recurrent or refractory solid tumors

Objectives:

    Primary Objectives:

    • Estimate the maximum tolerated dose (MTD) or recommended Phase 2 dose of temsirolimus administered in combination with irinotecan and temozolomide every 3 weeks to children with recurrent or refractory solid tumors
    • Define and describe the toxicities of the combination of temsirolimus, irinotecan, and temozolomide administered on this schedule

    Secondary Objectives:

    • Preliminarily define the antitumor activity of the combination of temsirolimus, irinotecan, and temozolomide within the confines of the Phase 1 study
    • Collect preliminary data regarding the biologic effects

      Key Eligibility Criteria:

      • > 12 months and ≤ 21 years of age
      • Measurable or evaluable solid tumors including CNS tumors (histological verification of malignancy at time of original diagnosis or relapse required except in patients with intrinsic brain stem tumors, optic pathway gliomas, and patients with pineal tumors with levations of serum or CSF alpha-fetoprotein or beta-HCG)
      • Current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with acceptable quality of life
      • Fully recovered from acute toxic effects of prior therapies that must have been completed within the specified time frames
      • Safety laboratory values and performance status must meet specified limits

      Study Outline:

      • Rolling six Phase I trial of temsirolimus in combination with irinotecan and temozolomide
      • Irinotecan (50 mg/m2/dose) and temozolomide (100 mg/m2/dose) will be administered orally daily x 5 every 3 weeks for a 21-day cycle
      • Temsirolimus will be administered intravenously (IV) over 30 minutes on Days 1 and 8 (beginning at 15 mg/m2/dose); the Day 1 dose will be given within 8 hours following administration of temozolomide and irinotecan; the cycle duration will be 21 days
      • Therapy may continue for up to 12 months in the absence of progressive disease or unacceptable toxicity
      • A minimum of two evaluable patients will be entered at each dose level for determination of maximum tolerated dose (MTD)
      • Once MTD has been defined, up to six additional patients with relapsed/refractory solid tumors may be enrolled to acquire additional safety data regarding this combination (assuming an inevaluability of 10 percent, a maximum of 34 patients is anticipated)

      Additional Information:

      • This trial will be conducted at the NIH Clinical Center in Bethesda, MD. It is open to patients who meet the eligibility requirements, regardless of where they live in the United States.
      • There is no charge for medical care received at NIH Clinical Center.
      • PDQ (Physicians Data Query) - provides additional details about this study for health care providers.


      Reviewed: 12/14/12
      Updated: 5/20/11

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