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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01431547
First received: September 7, 2011
Last updated: November 20, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Solid Tumors
Drug: dalotuzumab
Drug: ridaforolimus
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Monotherapy Dalotuzumab and Ridaforolimus-Dalotuzumab Combination Treatment in Pediatric Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of participants with dose limiting toxicities (DLTs) while receiving dalotuzumab alone [ Time Frame: First 21 days of treatment ] [ Designated as safety issue: Yes ]
  • Number of participants with DLTs while receiving dalotuzumab and ridaforolimus combination therapy [ Time Frame: First 21 days of treatment ] [ Designated as safety issue: Yes ]
  • Dalotuzumab mean serum trough concentration [ Time Frame: Day 22, pre-dose (Part 1) ] [ Designated as safety issue: No ]
  • Dalotuzumab mean serum trough concentration in combination therapy [ Time Frame: Day 22, pre-dose (Part 2) ] [ Designated as safety issue: No ]
  • Ridaforolimus geometric mean area under the concentration curve from Hour 0 to Hour 24 (AUC [0-24]) in combination therapy [ Time Frame: Cycle 1, Day 5 (Part 2) ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: February 2012
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Experimental: Parts 2 and 3: Dalotuzumab + ridaforolimus 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 Name: MK-8669

  Eligibility

Ages Eligible for Study:   3 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01431547     History of Changes
Other Study ID Numbers: 8669-062
Study First Received: September 7, 2011
Last Updated: November 20, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Antibodies, Monoclonal
Sirolimus
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 23, 2014