Pediatric Cancers
A Phase I Study of Monotherapy Dalotuzumab and Ridaforolimus-Dalotuzumab Combination Treatment in Pediatric Patients With Advanced Solid Tumors
NCI-12-C-0140, NCT01431547
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Investigator(s): |
Lee J. Helman, M.D.
Principal Investigator
Phone: 301-496-4257
Fax: 301-496-0775
helmanl@nih.gov
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Pediatric Oncology
Phone: 301-496-4256
1-877-624-4878 (Toll free)
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Background:
- Dalotuzumab (MK-0646), an IGF-1R monoclonal antibody inhibitor, and ridaforolimus (MK-8669), a
small molecule inhibitor of the mammalian target of rapamycin (mTOR), are currently in development for a variety of solid tumors
- In a Phase III study of adult sarcoma patients, ridaforolimus was associated with a decreased risk of progression versus placebo
- Objective anti-tumor activity has been observed with IGF1R inhibition in EWS; the rationale for inhibiting IGF-1R signaling in sarcoma is also strong, especially in Ewing's sarcoma, in which a EWS-FLI results in transactivation of IGF-IGF1R signaling
- Simultaneously inhibiting both targets may result in synergistic anti-tumor activity in that IGF1R blockage is known to abrogate feedback phosphorylation of AKT in the setting of targeted mTOR inhibition
- The ridaforolimus-dalotuzumab combination was generally well tolerated in adults in a Phase I dose escalation trial, and the ridaforolimus-dalotuzumab combination is expected to be well tolerated in children
Objectives:
- Mono-therapy Primary Objectives:
- To define the DLT and MTD of dalotuzumab when administered as monotherapy to children from 3 to < 18 years of age with advanced solid tumors
- Characterize the PK of dalotuzumab when administered as monotherapy to children from 3 to < 18 years of age with advanced solid tumors
- Combination Therapy Primary Objectives:
- To define the DLT and MT and to further characterize the safety and tolerability of ridaforolimus and dalotuzumab when administered in combination to children from 6 to < 18 years of age with advanced solid tumors
- Characterize the PK of ridaforolimus and dalotuzumab when administered in combination to children from 6 to < 18 years of age with advanced solid tumors
Key Eligibility Criteria:
- Pediatric patients ages 3 to < 18 for monotherapy and ages 6 to < 18 for combination therapy
- Diagnosis of a malignant solid tumor that has progressed despite standard therapy or for which no standard therapy is known
Study Outline:
- This study is a companion protocol to MK-8669 PN056, A Phase I Study of Ridaforolimus in Pediatric Patients with Advanced Solid Tumors; MK-8669 PN062 is a multi-center, open-label Phase I dose-escalation trial of intravenous dalotuzumab and ridaforolimus oral tablets to acquire safety, tolerability, and pharmacokinetic (PK) data for monotherapy dalotuzumab and combination treatment of ridaforolimus-dalotuzumab in children with advanced solid tumors
- This study will be conducted in three parts:
- Part 1 will be conducted as a dose escalation to gather safety and PK data on dalotuzumab as monotherapy
- Part 2 will be a dose escalation to gather safety and PK data for the ridaforolimus-dalotuzumab combination
- Part 3 will consist of an expansion cohort at the recommended pediatric Phase II dose (RP2D) of the combination to further assess safety, PK, and potential efficacy in a selected population
- Patients will be monitored carefully for the development of adverse experiences and will be monitored for clinical and/or radiographic evidence of disease progression according to usual standards of clinical practice; adverse experiences will be evaluated according to criteria outlined in the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0
- There will be no intra-patient dose escalation for patients enrolled on this study; for individual patients that experience dose-limiting toxicities, dose modification of ridaforolimus or dalotuzumab may be made
- Patients will be treated until disease progression, unacceptable toxicity, or the withdrawal of consent, and will be treated thereafter at the discretion of the physician
Additional Information:
- This trial will be conducted at the NIH Clinical Center in Bethesda, MD. It is open to patients who meet the eligibility requirements, regardless of where they live in the United States.
- There is no charge for medical care received at NIH Clinical Center.
- PDQ (Physicians Data Query) - provides additional details about this study for health care providers.
Reviewed: 12/14/12
Updated: 2/15/13
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