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

NCT ID: NCT01431547

Last Updated: 2016-06-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2013-09-30

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.

Conditions

Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Dalotuzumab

Group Type: EXPERIMENTAL

dalotuzumab

Intervention Type: DRUG

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

Parts 2 and 3: Dalotuzumab + ridaforolimus

Group Type: EXPERIMENTAL

dalotuzumab

Intervention Type: DRUG

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

ridaforolimus

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

MK-8669

Eligibility Criteria

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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

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.

Reference Type: RESULT

PMID: 27185573 (View on PubMed)

Other Identifiers

8669-062

Identifier Type: -

Identifier Source: org_study_id