A Study of Ridaforolimus in Pediatric Participants With Advanced Solid Tumors (MK-8669-056)

Phase 1

Terminated

• Conditions: Solid Tumors
• Interventions: Drug: Ridaforolimus

• Registration Number: NCT01431534
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-09-07
• Study First Submitted QC: 2011-09-07
• Study First Posted: 2011-09-09
• Study Start: 2012-01-30
• Primary Completion: 2013-08-20
• Study Completion: 2018-05-25
• Results First Submitted: 2018-10-29
• Status Verified: 2019-02
• Results First Submitted QC: 2019-02-27
• Last Update Submitted: 2019-02-27
• Results First Posted: 2019-03-01
• Last Update Posted: 2019-03-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ridaforolimus 22 mg/m^2	Ridaforolimus	Participants receive 22 mg/m\^2 of ridaforolimus administered orally for 5 consecutive days each week (2 days rest) in consecutive 28-day cycles for up to six months. Eligible participants can receive additional treatment in an extension phase of the study.
Ridaforolimus 28 mg/m^2	Ridaforolimus	Participants receive 28 mg/m\^2 of ridaforolimus administered orally for 5 consecutive days each week (2 days rest) in consecutive 28-day cycles for up to six months. Eligible participants can receive additional treatment in an extension phase of the study.
Ridaforolimus 33 mg/m^2	Ridaforolimus	Participants receive 33 mg/m\^2 of ridaforolimus administered orally for 5 consecutive days each week (2 days rest) in consecutive 28-day cycles for up to six months. Eligible participants can receive additional treatment in an extension phase of the study.

Primary Outcome Measures

Name	Time	Method
Number of Participants Experiencing a Dose Limiting Toxicity (DLT) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0)	Cycle 1 (cycle = 28 days)	DLT defined using NCI-CTCAE v.4.0 as any of the following events occurring during the first 28-day cycle that were possibly, probably, or definitely study drug-related: Grade 4 neutropenia for ≥5 days; Grade 3-4 neutropenia associated with fever, antibiotics, or hospitalization for infection; Grade 4 thrombocytopenia for ≥5 days or requiring platelet transfusion; ≥Grade 3 hyperglycemia for ≥5 days despite management; ≥Grade 3 diarrhea for \>24 hours despite management; ≥Grade 3 nausea or vomiting despite management; any other Grade ≥3 non-hematological toxicity persisting despite management (except alopecia, transient electrolyte abnormalities, transient Grade 3 liver function test elevations, and Grade 3 neurotoxicity for participants with baseline Grade 3 neurotoxicity); inability to complete DLT assessment period, interruption in dosing for \>10 dosing days during DLT assessment period, or any delay in the initiation of the next cycle for \>10 dosing days due to any related toxicity.
Area Under the Concentration-Time Curve of Ridaforolimus From Time 0 to 24 Hours (AUC0-24 hr)	Day 5 of Cycle 1 [28-day cycle]: pre-dose (0.0 hours) and 0.5, 1.0, 2.0, 4.0, 8.0, and 24.0 hours after administration of ridaforolimus	AUC is a measure of the amount of drug in the blood over time. Whole blood samples were collected pre-dose (within 5 minutes of ridaforolimus administration) and post-dose at specified time points on Day 5 of the first week of Cycle 1 to determine AUC0-24 hr.