A Study of Ridaforolimus in Pediatric Participants With Advanced Solid Tumors (MK-8669-056)
Condition: Solid Tumors
MeSH terms: Neoplasms
Intervention: Ridaforolimus
Intervention description: Oral administration of 10 mg enteric-coated tablets at doses of 22 mg/m^2, 28 mg/m^2, or 33 mg/m^2 based on body surface area (BSA), once daily for 5 consecutive days each week in consecutive 28-day cycles.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 6 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      The main objectives of this trial are to determine the recommended dose of ridaforolimus for
      pediatric participants with advanced solid tumors by measuring the number of participants
      experiencing dose-limiting toxicities (DLTs) while on different doses of ridaforolimus, and
      to characterize the pharmacokinetics of ridaforolimus in these participants. The primary
      hypotheses of this study are that 1) the DLTs observed will be dose-dependent and allow for
      definition of a maximum tolerated dose (MTD) and 2) at a safe and well tolerated dose,
      ridaforolimus geometric mean (GM) Day-5 blood area under the concentration-time curve at 24
      hours (AUC0-24) exceeds 75% (or 1304-ng*hr/mL) of the estimated GM Day-5, 40-mg AUC0-24 in
      adults.

      Study-related visits concluded in August 2013. Participants who did not have disease
      progression, adequately tolerated therapy, and continued to meet eligibility criteria for 6
      months after the enrollment period had been completed could continue treatment in an
      extension phase until they met discontinuation criteria or voluntarily withdrew.
    

Eligibility criteria:

        Inclusion criteria:

          -  Histologic or cytologic diagnosis of a malignant solid tumor, including tumors of the
             central nervous system and lymphoma, that have progressed despite standard therapy or
             for which no effective standard therapy is known. Participants who have received
             standard therapy and continue to have biopsy-proven residual stable disease are
             eligible

          -  Measurable or non-measurable disease

          -  Must be able to swallow tablets

          -  Performance Status: Lansky Play Scale ≥70 for children <10 years of age; Karnofsky
             score ≥70 for children ≥10 to <16 years; or Eastern Cooperative Oncology Group (ECOG)
             Status 0-2 for patients age 16 and older

          -  Adequate organ function

          -  For females of reproductive potential, a negative pregnancy test must be documented
             within 72 hours of receiving the first dose of study medication

          -  Participants of reproductive potential must agree to use (or have their partner use)
             adequate contraception throughout the study, starting with Visit 1 through 30 days
             after the last dose of study drug

        Exclusion criteria:

          -  Currently receiving any other investigational agents or using any investigational
             devices

          -  Leukemia

          -  Participant previously received ridaforolimus, rapamycin, or other rapamycin analogs

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to ridaforolimus

          -  Persistent acute toxicity from previous therapy ≥Grade 2 (excluding alopecia,
             neuropathy, or hearing loss)

          -  Uncontrolled intercurrent illness despite adequate therapy

          -  Pregnant or breastfeeding

          -  Requirement for concurrent treatment with medications that are inducers or inhibitors
             of cytochrome P450 (CYP3A)

          -  Poorly controlled Type 1 or 2 diabetes