Study of Dalotuzumab Alone and With Ridaforolimus in Pediatric Participants With Advanced Solid Tumors (MK-8669-062 AM1)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I Study of Monotherapy Dalotuzumab and Ridaforolimus-Dalotuzumab Combination Treatment in Pediatric Patients With Advanced Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: dalotuzumab
* Drug: dalotuzumab
* Drug: ridaforolimus


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dalotuzumab<br> | Drug: dalotuzumab<br>* 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<br>|
| Experimental: Parts 2 and 3: Dalotuzumab + ridaforolimus<br> | Drug: dalotuzumab<br>* For Part 2: dalotuzumab IV over 60 minutes every three weeks, dose based on participant BSA, starting at the lowest tolerated dose that met PK target levels in Part 1. For Part 3: dalotuzumab IV over 60 minutes every three weeks, dose based on participant BSA, at the dose level identified for combination therapy in Part 2<br>Drug: ridaforolimus<br>* 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<br>* Other names: MK-8669;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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) |