A Study of Robatumumab (SCH 717454, MK-7454) in Combination With Different Treatment Regimens in Pediatric Participants With Advanced Solid Tumors (P05883, MK-7454-006)

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 1

Conditions: Neuroblastoma; Kidney Tumor; Neoplasms; Solid Tumors; Bone Cancer

Treatments: Drug: Etoposide; Drug: Ifosfamide; Drug: Doxorubicin; Drug: Vincristine; Biological: Robatumumab; Drug: Cyclophosphamide; Drug: Temozolomide; Drug: Irinotecan

Study type: Interventional

Funder types: Industry

Identifiers

NCT00960063

P05883

MK-7454-006 (Other Identifier)

Details and patient eligibility

About

This is a Phase 1/1B, non-randomized, open-label, dose-escalation study of robatumumab (SCH 717454, MK-7454) administered in combination with chemotherapy in pediatric participants with solid tumors, to be conducted in conformance with Good Clinical Practices. This study will evaluate the safety, tolerability and dose-finding of robatumumab when administered in combination with temozolomide and irinotecan (Arm A); or cyclophosphamide, doxorubicin, and vincristine (Arm B), or ifosfamide and etoposide (Arm C).

The primary study hypothesis is that robatumumab can be safely administered in combination with chemotherapy regimens in pediatric participants with solid tumors.

Enrollment: 4 patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Must be <= 21 years of age (older participants may be allowed on study on a case-by-case basis); may be of either sex, and of any race/ethnicity.
• Must have histologic confirmation of the advanced solid tumor, except for brainstem tumors.
• Must have Karnofsky performance score of >=50 (if participant is >16 years of age) or a Lansky score of >50 (if participant is <=16 years of age).
• Must have adequate organ function during Screening.
• Must be able to adhere to dose and visit schedules.

Exclusion criteria

• Must not have a history of another malignancy.
• Must not have uncontrolled diabetes mellitus.
• Must not have persistent, unresolved common terminology criteria for adverse events (CTCAE) Grade >=2 drug-related toxicity associated with previous treatment.
• Must not have known hypersensitivity to other antibodies, or any accompanying excipients associated with these medications.
• If female, must not be breast-feeding, pregnant, intending to become pregnant, or have a positive pregnancy test at Screening.
• Must not be known to have human immunodeficiency virus (HIV) infection or known HIV-related malignancy.
• Must not be known to have active Hepatitis B, or Hepatitis C.
• Must not have any serious or uncontrolled infection.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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4 participants in 3 patient groups

Temozolomide+Irinotecan+Robatumumab

Experimental group

Description:

Participants receive temozolomide 100 mg/m\^2/day intravenously (IV) on Days 1-5 PLUS irinotecan 10 mg/m\^2/day IV on Days 1-5 and Days 8-12 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle.

Treatment:

Biological: Robatumumab

Drug: Temozolomide

Drug: Irinotecan

Vincristine+Doxorubicin+Cyclophosphamide+Robatumumab

Experimental group

Description:

Participants receive vincristine 2 mg/m\^2 (maximum 2 mg) IV on Day 1 PLUS cyclophosphamide 1200 mg/m\^2 IV on Day 1 PLUS doxorubicin hydrochloride 75 mg/m\^2 IV continuously over 48 hours PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle.

Treatment:

Biological: Robatumumab

Drug: Cyclophosphamide

Drug: Doxorubicin

Drug: Vincristine

Ifosfamide+Etoposide+Robatumumab

Experimental group

Description:

Participants receive ifosfamide 1800 mg/m\^2 per day IV PLUS etoposide 100 mg/m\^2 per day IV on Days 1-5 PLUS robatumumab 10 mg/kg or 20 mg/kg IV on Day 1 of each 3-week cycle.

Treatment:

Biological: Robatumumab

Drug: Ifosfamide

Drug: Etoposide