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

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:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Merck:

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 ]

Estimated Enrollment:	60
Study Start Date:	February 2012
Estimated Study Completion Date:	October 2013
Estimated Primary Completion Date:	October 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

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
ClinicalTrials.gov Identifier:	NCT01431547 History of Changes
Other Study ID Numbers:	8669-062
Study First Received:	September 7, 2011
Last Updated:	May 10, 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 May 16, 2013