Clinical trial NCT01431534: A Study of Ridaforolimus in Pediatric Participants With Advanced Solid Tumors (MK-8669-056)
Official title: A Phase I Study of Ridaforolimus in Pediatric Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-09-09
Enrollment: 20
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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)
timeFrame: Cycle 1 (cycle = 28 days)
measure: Area Under the Concentration-Time Curve of Ridaforolimus From Time 0 to 24 Hours (AUC0-24 hr)
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Pearson AD, Federico SM, Aerts I, Hargrave DR, DuBois SG, Iannone R, Geschwindt RD, Wang R, Haluska FG, Trippett TM, Geoerger B. A phase 1 study of oral ridaforolimus in pediatric patients with advanced solid tumors. Oncotarget. 2016 Dec 20;7(51):84736-84747. doi: 10.18632/oncotarget.12450.