Clinical trial NCT00960063: 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)
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 (Protocol No. 05883)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Neoplasms
Solid Tumors
Bone Cancer
Kidney Tumor
Neuroblastoma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2009-08-17
Enrollment: 4
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities
timeFrame: Up to ~30 days after last dose of study drug (Up to ~10.3 months)
Secondary outcomes:
measure: Best Overall Response Based on Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Screening, every 6 weeks and at ~30 days after last dose of study drug (Up to ~10.3 months)
measure: Maximum Observed Concentration (Cmax) of Robatumumab
timeFrame: 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
measure: Plasma Level of Insulin-like Growth Factor-I (IGF-I)
timeFrame: On Day 1 of Cycles 1, 2, 3 and 5, and ~30 days after last dose of study drug (Up to~10.3 months)
measure: Number of Participants Who Developed Anti-robatumumab Antibodies
timeFrame: 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)
measure: Time to Maximum Observed Concentration (Tmax) of Robatumumab
timeFrame: 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
measure: Area Under the Curve at the Time of Final Quantifiable Sample (AUCtf) for Robatumumab
timeFrame: 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
measure: Area Under the Curve During a Dosing Interval τ (AUCτ) for Robatumumab
timeFrame: 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
measure: Plasma Level of Insulin-like Growth Factor-2 (IGF-II)
timeFrame: On Day 1 of Cycles 1, 2, 3 and 5, and ~30 days after last dose of study drug (Up to~10.3 months)
measure: Plasma Level of Insulin-like Growth Factor Binding Protein-2 (IGFBP-2)
timeFrame: On Day 1 of Cycles 1, 2, 3 and 5, and ~30 days after last dose of study drug (Up to~10.3 months)
measure: Plasma Level of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3)
timeFrame: On Day 1 of Cycles 1, 2, 3 and 5, and ~30 days after last dose of study drug (Up to~10.3 months)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: