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

NCT01431547 | Completed Phase 1

• 1 other identifier: 8669-062
• Study Type: interventional
• Target: 21
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (5)

• 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)

Study Arms (2)

Part 1: Dalotuzumab

EXPERIMENTAL

Drug: dalotuzumab

Parts 2 and 3: Dalotuzumab + ridaforolimus

EXPERIMENTAL

Drug: dalotuzumab; Drug: ridaforolimus

Interventions

dalotuzumab 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

Part 1: Dalotuzumab

ridaforolimus 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

Also known as: MK-8669

Parts 2 and 3: Dalotuzumab + ridaforolimus

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 27185573 RESULT

MeSH Terms

Interventions

dalotuzumab; ridaforolimus

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2011
• First Posted: September 9, 2011
• Study Start: February 1, 2012
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: June 17, 2016

Record last verified: 2016-06