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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00960063
First received: August 14, 2009
Last updated: January 30, 2014
Last verified: January 2014
  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 Intervention Phase
Neoplasms
Solid Tumors
Bone Cancer
Kidney Tumor
Neuroblastoma
Drug: Temozolomide, Irinotecan, and SCH 717454
Drug: Vincristine, Doxorubicin, Cyclophosphamide (CAV), and SCH 717454
Drug: Ifosfamide, Etoposide (IE), and SCH 717454
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

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 ]

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 ]

Enrollment: 4
Study Start Date: November 2009
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Temozolomide, Irinotecan, and SCH 717454 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.
Experimental: Arm B: Vincristine, Doxorubicin, Cyclophosphamide, SCH 717454 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.

Experimental: Arm C: Ifosfamide, Etoposide (IE), and 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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00960063     History of Changes
Other Study ID Numbers: P05883
Study First Received: August 14, 2009
Last Updated: January 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Neuroblastoma
Kidney Neoplasms
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Cyclophosphamide
Temozolomide
Ifosfamide
Isophosphamide mustard
Irinotecan
Etoposide phosphate
Liposomal doxorubicin
Etoposide
Doxorubicin
Vincristine
Antibodies, Monoclonal
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014