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)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 4
- 主要终点
- Number of Participants With Dose Limiting Toxicities
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Temozolomide+Irinotecan+Robatumumab
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.
干预措施: Temozolomide (Drug)
Temozolomide+Irinotecan+Robatumumab
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.
干预措施: Irinotecan (Drug)
Temozolomide+Irinotecan+Robatumumab
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.
干预措施: Robatumumab (Biological)
Vincristine+Doxorubicin+Cyclophosphamide+Robatumumab
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.
干预措施: Vincristine (Drug)
Vincristine+Doxorubicin+Cyclophosphamide+Robatumumab
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.
干预措施: Robatumumab (Biological)
Vincristine+Doxorubicin+Cyclophosphamide+Robatumumab
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.
干预措施: Doxorubicin (Drug)
Vincristine+Doxorubicin+Cyclophosphamide+Robatumumab
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.
干预措施: Cyclophosphamide (Drug)
Ifosfamide+Etoposide+Robatumumab
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.
干预措施: Ifosfamide (Drug)
Ifosfamide+Etoposide+Robatumumab
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.
干预措施: Robatumumab (Biological)
Ifosfamide+Etoposide+Robatumumab
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.
干预措施: Etoposide (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities
时间窗: Up to ~30 days after last dose of study drug (Up to ~10.3 months)
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.
次要结局
- 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)
- 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))
- Plasma Level of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3)(On Day 1 of Cycles 1, 2, 3 and 5, and ~30 days after last dose of study drug (Up to~10.3 months))
- 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))
- 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)
- Area Under the Curve at the Time of Final Quantifiable Sample (AUCtf) for 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)
- Area Under the Curve During a Dosing Interval τ (AUCτ) for 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-2 (IGF-II)(On Day 1 of Cycles 1, 2, 3 and 5, and ~30 days after last dose of study drug (Up to~10.3 months))
- Plasma Level of Insulin-like Growth Factor Binding Protein-2 (IGFBP-2)(On Day 1 of Cycles 1, 2, 3 and 5, and ~30 days after last dose of study drug (Up to~10.3 months))