Clinical trial NCT01431547: Study of Dalotuzumab Alone and With Ridaforolimus in Pediatric Participants With Advanced Solid Tumors (MK-8669-062 AM1)
Official title: A Phase I Study of Monotherapy Dalotuzumab and Ridaforolimus-Dalotuzumab Combination Treatment in Pediatric Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-09-09
Enrollment: 21
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of participants with dose limiting toxicities (DLTs) while receiving dalotuzumab alone
timeFrame: First 21 days of treatment
measure: Number of participants with DLTs while receiving dalotuzumab and ridaforolimus combination therapy
timeFrame: First 21 days of treatment
measure: Dalotuzumab mean serum trough concentration
timeFrame: Day 22, pre-dose (Part 1)
measure: Dalotuzumab mean serum trough concentration in combination therapy
timeFrame: Day 22, pre-dose (Part 2)
measure: Ridaforolimus geometric mean area under the concentration curve from Hour 0 to Hour 24 (AUC [0-24]) in combination therapy
timeFrame: Cycle 1, Day 5 (Part 2)
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: 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.