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

Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01431547
• Other study ID #: 8669-062
• Status: Completed
• Phase: Phase 1
• First received: September 7, 2011
• Last updated: June 16, 2016
• Start date: February 2012
• Est. completion date: September 2013

Study information

• Verified date: June 2016
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 17 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumors

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & 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 adv — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with dose limiting toxicities (DLTs) while receiving dalotuzumab alone		First 21 days of treatment	Yes
Primary	Number of participants with DLTs while receiving dalotuzumab and ridaforolimus combination therapy		First 21 days of treatment	Yes
Primary	Dalotuzumab mean serum trough concentration		Day 22, pre-dose (Part 1)	No
Primary	Dalotuzumab mean serum trough concentration in combination therapy		Day 22, pre-dose (Part 2)	No
Primary	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)	No