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)

NCT00960063 | Terminated Phase 1 Results

• 2 other identifiers: P05883MK-7454-006
• Study Type: interventional
• Target: 4
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose Limiting Toxicities

  Dose-limiting toxicity was defined by the following adverse events (AEs) that were considered possibly or probably related to either robatumumab or to its interaction with the chemotherapy regimen assigned: neutropenia (Grade 4 for \>1 week that did not resolve prior to Day 1 of the next cycle; Grade 3-4 neutropenia with Grade ≥2 fever lasting 3 days; neutropenic infection; failure to recover to study entry/eligibility criteria laboratory requirement levels that resulted in a delay of 14 days between treatment cycles), thrombocytopenia (Grade 4 for \>1 week that did not resolve prior to Day 1 of the next cycle; Grade 3-4 requiring a platelet transfusion on 2 separate days within a cycle) or all other AEs (Grade ≥3 \[any duration\] not ameliorable by supportive or symptomatic measures). The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.0) was to be used to grade AEs.

  Up to ~30 days after last dose of study drug (Up to ~10.3 months)

Secondary Outcomes (10)

• Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST)

  Screening, every 6 weeks and at ~30 days after last dose of study drug (Up to ~10.3 months)

• Maximum Observed Concentration (Cmax) of Robatumumab

  Cycles 1 & 2: pre- and post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post start of infusion; then pre-and post-dose in odd-numbered cycles, and Post Study Visits 1 and 2

• Plasma Level of Insulin-like Growth Factor-I (IGF-I)

  On Day 1 of Cycles 1, 2, 3 and 5, and ~30 days after last dose of study drug (Up to~10.3 months)

• Number of Participants Who Developed Anti-robatumumab Antibodies

  Prior to 1st and 8th doses of robatumumab, ~30 days after last dose of study drug, and 4 months after last dose of study drug (Up to ~13.3 months)

• Time to Maximum Observed Concentration (Tmax) of Robatumumab

  Cycles 1 & 2: pre- and post-infusion, and at 3, 6, 24, 48, 168, 336, and 504 hours post start of infusion; then pre-and post-dose in odd-numbered cycles, and Post Study Visits 1 and 2

Study Arms (3)

Temozolomide+Irinotecan+Robatumumab

EXPERIMENTAL

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.

Drug: Temozolomide; Drug: Irinotecan; Biological: Robatumumab

Vincristine+Doxorubicin+Cyclophosphamide+Robatumumab

EXPERIMENTAL

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.

Drug: Vincristine; Biological: Robatumumab; Drug: Doxorubicin; Drug: Cyclophosphamide

Ifosfamide+Etoposide+Robatumumab

EXPERIMENTAL

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.

Drug: Ifosfamide; Biological: Robatumumab; Drug: Etoposide

Interventions

Temozolomide DRUG

Temozolomide+Irinotecan+Robatumumab

Vincristine DRUG

Vincristine+Doxorubicin+Cyclophosphamide+Robatumumab

Ifosfamide DRUG

Ifosfamide+Etoposide+Robatumumab

Irinotecan DRUG

Temozolomide+Irinotecan+Robatumumab

Robatumumab BIOLOGICAL

Ifosfamide+Etoposide+Robatumumab; Temozolomide+Irinotecan+Robatumumab; Vincristine+Doxorubicin+Cyclophosphamide+Robatumumab

Doxorubicin DRUG

Vincristine+Doxorubicin+Cyclophosphamide+Robatumumab

Cyclophosphamide DRUG

Vincristine+Doxorubicin+Cyclophosphamide+Robatumumab

Etoposide DRUG

Ifosfamide+Etoposide+Robatumumab

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Neoplasms; Bone Neoplasms; Carcinoma, Renal Cell; Neuroblastoma

Interventions

Temozolomide; Vincristine; Ifosfamide; Irinotecan; robatumumab; Doxorubicin; Cyclophosphamide; Etoposide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Oxazines; Camptothecin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2009
• First Posted: August 17, 2009
• Study Start: November 11, 2009
• Primary Completion: December 22, 2010
• Study Completion: December 22, 2010
• Last Updated: August 27, 2018
• Results First Posted: February 10, 2016

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share