Solid Tumors
Conditions
Brief summary
This is a study of dalotuzumab given as monotherapy and in combination with ridaforolimus for pediatric participants with advanced solid tumors. This study will have three parts. Part 1 will find a maximum tolerated dose (MTD) and collect pharmacokinetic (PK) data for dalotuzumab alone. Part 2 will find an MTD and collect PK data for dalotuzumab in combination with ridaforolimus. Part 3 will be an expansion cohort at the recommended Phase 2 dose (RPTD) found in Part 2 to confirm the RPTD and look at the potential efficacy of the combination therapy.
Interventions
DRUGdalotuzumab
For Part 1: dalotuzumab, intravenously (IV) over 60 minutes every three weeks, dose based on participant body surface area (BSA), starting dose of 900 mg/m\^2, and escalated for successive cohorts of participants until MTD is found
DRUGridaforolimus
For Part 2: ridaforolimus 10 mg enteric coated tablets, orally, on 5 consecutive days each week, dose based on participant BSA, at 1 dose level lower than the MTD or highest dose level used in the companion study MK-8669-056. For Part 3:ridaforolimus 10 mg enteric coated tablets, orally, on 5 consecutive days each week, dose based on participant BSA, at the dose level identified for combination therapy in Part 2
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Participants of age 3 to 17 years for Part 1 of the study and age 6 to 17 years for Parts 2 and 3 of the study * 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. * Measurable or non-measurable disease for Parts 1 and 2; measurable disease for Part 3 * Parts 2 and 3: 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 * Previously received dalotuzumab or other IGF-1R inhibitors for Part 1 * History of allergic reactions attributed to compounds of similar chemical or biologic composition to dalotuzumab or ridaforolimus * Persistent acute toxicity from previous therapy ≥Grade 2 (excluding alopecia, neuropathy, or hearing loss) * Uncontrolled intercurrent illness despite adequate therapy * Pregnant or breastfeeding * For Parts 2 and 3: requirement for concurrent treatment with medications that are inducers or inhibitors of cytochrome P450 (CYP3A) * Poorly controlled Type 1 or 2 diabetes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with dose limiting toxicities (DLTs) while receiving dalotuzumab alone | First 21 days of treatment |
| Number of participants with DLTs while receiving dalotuzumab and ridaforolimus combination therapy | First 21 days of treatment |
| Dalotuzumab mean serum trough concentration | Day 22, pre-dose (Part 1) |
| Dalotuzumab mean serum trough concentration in combination therapy | Day 22, pre-dose (Part 2) |
| Ridaforolimus geometric mean area under the concentration curve from Hour 0 to Hour 24 (AUC [0-24]) in combination therapy | Cycle 1, Day 5 (Part 2) |
Outcome results
None listed