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

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

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: dalotuzumab; Drug: dalotuzumab; Drug: ridaforolimus

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dalotuzumab	Drug: dalotuzumab; 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; Drug: dalotuzumab; 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
Experimental: Parts 2 and 3: Dalotuzumab + ridaforolimus	Drug: dalotuzumab; 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; Drug: dalotuzumab; 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; Drug: ridaforolimus; 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; Other Names: MK-8669

What is the study measuring?

Primary Outcome Measures

Outcome 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)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Frappaz D, Federico SM, Pearson AD, Gore L, Macy ME, DuBois SG, Aerts I, Iannone R, Geschwindt R, Van Schanke A, Wang R, Geoerger B. Phase 1 study of dalotuzumab monotherapy and ridaforolimus-dalotuzumab combination therapy in paediatric patients with advanced solid tumours. Eur J Cancer. 2016 Jul;62:9-17. doi: 10.1016/j.ejca.2016.03.084. Epub 2016 May 10.

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: September 7, 2011
• First Submitted That Met QC Criteria: September 7, 2011
• First Posted (Estimate): September 9, 2011

Study Record Updates

• Last Update Posted (Estimate): June 17, 2016
• Last Update Submitted That Met QC Criteria: June 16, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: 8669-062