A Study of SCH 717454 in Combination With Different Treatment Regimens in Pediatric Subjects With Advanced Solid Tumors (Study P05883) | RxWiki

A Study of SCH 717454 in Combination With Different Treatment Regimens in Pediatric Subjects With Advanced Solid Tumors (Study P05883)

Overview[ - collapse ][ - ]

Purpose	Hypothesis: SCH 717454 can be safely administered in combination with chemotherapy regimens in pediatric subjects. This is a Phase 1/1B, non-randomized, open-label, dose-escalation study of SCH 717454 administered in combination with chemotherapy in pediatric subjects with solid tumors, to be conducted in conformance with Good Clinical Practices. This study has three independent arms that consist of an evaluation of the safety, tolerability, and dose-finding of SCH 717454 when administered in combination with temozolomide and irinotecan (Arm A); or cyclophosphamide, doxorubicin, and vincristine (Arm B), or ifosfamide and etoposide (Arm C).
Condition	Neoplasms Solid Tumors Bone Cancer Kidney Tumor Neuroblastoma
Intervention	Drug: Temozolomide, Irinotecan, and SCH 717454 Drug: Vincristine, Doxorubicin, Cyclophosphamide (CAV), and SCH 717454 Drug: Ifosfamide, Etoposide (IE), and SCH 717454
Phase	Phase 1
Sponsor	Merck Sharp & Dohme Corp.
Responsible Party	Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier	NCT00960063
First Received	August 14, 2009
Last Updated	January 30, 2014
Last verified	January 2014

Tracking Information[ + expand ][ + ]

First Received Date	August 14, 2009
Last Updated Date	January 30, 2014
Start Date	November 2009
Estimated Primary Completion Date	December 2010
Current Primary Outcome Measures	All Dose Limiting Toxicities tabulated by treatment arm and dose level [Time Frame: From beginning of treatment to approximately 30 days after the final dose of SCH 717454 or the standard treatment assigned (whichever is last). Data will be collected at all visits.] [Designated as safety issue: Yes]
Current Secondary Outcome Measures	To obtain preliminary information on the RECIST-determined response rate for SCH 717454 administered in combination with different treatment agents [Time Frame: Data will be collected at Screening, every 6 weeks and 30 days after the final dose of SCH 717454 or the standard treatment assigned (whichever is last).] [Designated as safety issue: No] Pharmacokinetic parameters of SCH 717454 in pediatric population will be evaluated. Summary statistics (eg, means and coefficients of variation) will be provided for the concentration data. [Time Frame: From beginning of treatment to 4 months after last dose of SCH 717454] [Designated as safety issue: No] The pharmacodynamic effects of SCH 717454 in pediatric population will be assessed. Absolute levels and changes in pharmacodynamic measurements will be compared among each other and with clinical outcome, in terms of both toxicity and efficacy. [Time Frame: On Day 1 of: Cycles 1, 2, 3, 5, and approximately 30 days after the final dose of SCH 717454 or the standard treatment assigned (whichever is last).] [Designated as safety issue: No] The incidence of anti-SCH 717454 antibodies. [Time Frame: Prior to 1st and 8th dose of SCH 717454, approximately 30 days after the final dose of SCH 717454 or the standard treatment assigned (whichever is last), and 4 months after last dose of SCH 717454.] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief Title	A Study of SCH 717454 in Combination With Different Treatment Regimens in Pediatric Subjects With Advanced Solid Tumors (Study P05883)
Official Title	A Phase 1/1B Dose-Escalation Study to Determine the Safety and Tolerability of SCH 717454 Administered in Combination With Chemotherapy in Pediatric Subjects With Advanced Solid Tumors P05883
Brief Summary	Hypothesis: SCH 717454 can be safely administered in combination with chemotherapy regimens in pediatric subjects. This is a Phase 1/1B, non-randomized, open-label, dose-escalation study of SCH 717454 administered in combination with chemotherapy in pediatric subjects with solid tumors, to be conducted in conformance with Good Clinical Practices. This study has three independent arms that consist of an evaluation of the safety, tolerability, and dose-finding of SCH 717454 when administered in combination with temozolomide and irinotecan (Arm A); or cyclophosphamide, doxorubicin, and vincristine (Arm B), or ifosfamide and etoposide (Arm C).
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 1
Study Design	Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Neoplasms Solid Tumors Bone Cancer Kidney Tumor Neuroblastoma
Intervention	Drug: Temozolomide, Irinotecan, and SCH 717454 Temozolomide 100 mg/m2/day on Days 1-5; and irinotecan 10 mg/m2/day IV on Days 1-5 and Days 8-12 and SCH 717454 on Day 1. Drug: Vincristine, Doxorubicin, Cyclophosphamide (CAV), and SCH 717454 Vincristine 2 mg/m2 (max 2mg) on Day 1; Cyclophosphamide 1200 mg/m2 IV on Day 1, Doxorubicin hydrochloride 75 mg/m2 IV continuously over 48 hours (dactinomycin 1.25 mg/m2 can be substituted for doxorubicin after Cycle 1, when a total doxorubicin dose of 450 mg/m2 is reached). SCH 717454 on Day 1 Subjects with high risk Ewing's sarcoma may be enrolled on Arm B on a case-by-case basis, and if they tolerate the combination during the first cycle, may then be treated with alternating cycles of treatment of CAV and ifosfamide/etoposide (IE) in combination with SCH 717454. Drug: Ifosfamide, Etoposide (IE), and SCH 717454 Ifosfamide 1800 mg/m2 per day IV and etoposide 100 mg/m2 per day IV on Days 1-5 with SCH 717454 on Day 1.
Study Arm (s)	Experimental: Arm A: Temozolomide, Irinotecan, and SCH 717454 Experimental: Arm B: Vincristine, Doxorubicin, Cyclophosphamide, SCH 717454 Experimental: Arm C: Ifosfamide, Etoposide (IE), and SCH 717454

Recruitment Information[ + expand ][ + ]

Recruitment Status	Terminated
Estimated Enrollment	4
Estimated Completion Date	December 2010
Estimated Primary Completion Date	December 2010
Eligibility Criteria	Inclusion Criteria: - Each subject must be <= 21 years of age (older subjects may be allowed on study on a case-by-case basis). A subject may be of either sex, and of any race/ethnicity. - Each subject must have histologic confirmation of the advanced solid tumor, except for brainstem tumors. - Each subject must have Karnofsky performance score of >= 50 (if subject is > 16 years of age) or a Lansky score of > 50 (if subject is <= 16 years of age). - Each subject must have adequate organ function during Screening. - Each subject must be able to adhere to dose and visit schedules. Exclusion Criteria: - A subject must not have a history of another malignancy. - A subject must not have uncontrolled diabetes mellitus. - A subject must not have persistent, unresolved common terminology criteria for adverse events (CTCAE) Grade >=2 drug-related toxicity associated with previous treatment. - A subject must not have known hypersensitivity to other antibodies, or any accompanying excipients associated with these medications. - A female subject must not be breast-feeding, pregnant, intending to become pregnant, or have a positive pregnancy test at Screening. - A subject must not be known to have human immunodeficiency virus (HIV) infection or known HIV-related malignancy. - A subject must not be known to have active Hepatitis B, or Hepatitis C. - A subject must not have any serious or uncontrolled infection.
Gender	Both
Ages	N/A
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	Not Provided

Administrative Information[ + expand ][ + ]

NCT Number	NCT00960063
Other Study ID Numbers	P05883
Has Data Monitoring Committee	No
Information Provided By	Merck Sharp & Dohme Corp.
Study Sponsor	Merck Sharp & Dohme Corp.
Collaborators	Not Provided
Investigators	Not Provided
Verification Date	January 2014