A Phase II Trial of R1507, a Recombinant Human Monoclonal Antibody to the Insulin-Like Growth Factor-1 Receptor for the Treatment of Participants With Recurrent or Refractory Ewing's Sarcoma, Osteosarcoma, Synovial Sarcoma, Rhabdomyosarcoma and Other Sarcomas.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 317
- 试验地点
- 41
- 主要终点
- Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8
研究概览
简要总结
The study was primarily designed to determine objective response, progression-free survival (PFS), and the safety and tolerability of R1507 in participants with recurrent or refractory Ewing's sarcoma, osteosarcoma, synovial sarcoma, rhabdomyosarcoma and other sarcomas including alveolar soft part sarcoma, desmoplastic small round cell tumor, extraskeletal myxoid chondrosarcoma, clear cell sarcoma, and myxoid liposarcoma.
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
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •progressive, recurrent or refractory Ewing's sarcoma, or recurrent or refractory osteosarcoma, synovial sarcoma, rhabdomyosarcoma, or other sarcomas of the following sub-types: alveolar soft part sarcoma, desmoplastic small round cell tumor, extraskeletal myxoid chondrosarcoma, clear cell sarcoma and myxoid liposarcoma;
- •Cohort 3 only: age must be >= 2 and <= 21 years
排除标准
- •clinically significant unrelated systemic illness which would compromise the participant's ability to tolerate the investigational agent, or interfere with the study procedures or results;
- •known hypersensitivity to any of the components of R1507 or prior hypersensitivity reactions to monoclonal antibodies;
- •treatment (within the past 2 weeks) with pharmacologic doses of corticosteroids or other immunosuppressive agents;
- •current or prior therapy with insulin-like growth factor (IGF) inhibitor (monoclonal or specific kinase inhibitor);
- •history of solid organ transplant;
- •other malignant disease diagnosed within the previous 5 years, excluding intra-epithelial cervical neoplasia or non-melanoma skin cancer;
- •active central nervous system disease
研究组 & 干预措施
Cohort 1: Ewings Sarcoma Primary Cohort
Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 1 includes individuals with Ewing's sarcoma who have relapsed within 24 weeks after diagnosis and have received two or more prior chemotherapy regimens.
干预措施: RG1507 (Drug)
Cohort 2: Ewings Sarcoma Secondary Cohort
Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.
干预措施: RG1507 (Drug)
Cohort 3: Ewings Sarcoma Expanded Cohort
Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.
干预措施: RG1507 (Drug)
Cohort 4: Osteosarcoma
Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.
干预措施: RG1507 (Drug)
Cohort 5: Synovial Sarcoma
Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.
干预措施: RG1507 (Drug)
Cohort 6: Rhabdomyosarcoma
Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.
干预措施: RG1507 (Drug)
Cohort 7a: Alveolar Soft Part Sarcoma
Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a includes individuals with alveolar soft part sarcoma.
干预措施: RG1507 (Drug)
Cohort 7b: Desmoplastic Small Round Cell Tumors.
Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.
干预措施: RG1507 (Drug)
Cohort 7c: Extraskeletal Myxoid Chondrosarcoma
Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.
干预措施: RG1507 (Drug)
Cohort 7d: Clear Cell Sarcoma
Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.
干预措施: RG1507 (Drug)
Cohort 7e: Myxoid Liposarcoma
Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.
干预措施: RG1507 (Drug)
Cohort 8: Diagnosis Not Specified
Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.
干预措施: RG1507 (Drug)
结局指标
主要结局
Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8
时间窗: Baseline up to 6 years (assessed at baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression)
Complete response is the disappearance of all known disease, determined by two consecutive observations not less than 4 weeks apart. Partial response is \>=50% decrease in the total tumor load of the lesions that have been measured to determine the effect of therapy not less than four weeks apart. The observations must be consecutive.
Progression-Free Survival (PFS) Rate According to WHO Response Criteria at 18 Weeks From Start of R2607 Treatment in Cohort 1
时间窗: Baseline up to 18 weeks (assessed at baseline, every 6 weeks until disease progression)
The PFS survival rate is a landmark analysis of progression-free survival at 18 weeks from start of treatment. Progression-free survival rate at 18 weeks is a dichotomous endpoint, with a patient categorized as alive (with either stable disease or objective response) at 18 weeks from start of treatment.
Percentage of Participants With Adverse Events (AEs) in Cohort 1 and 2
时间窗: Baseline up to 6 years
次要结局
- Percentage of Participants With Complete or Partial Response According to WHO Response Criteria in Cohort 1(Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years))
- PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8(Baseline, every 6 weeks until disease progression (up to 18 weeks))
- Percentage of Participants With AEs in Cohorts 3-8(Baseline up to 6 years)
- Duration of Response (DOR) According to WHO Response Criteria in Cohorts 1 to 8(Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years))
- Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8(Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years))
- Failure-Free Survival (FFS) According to WHO Response Criteria in Cohorts 1 to 8(Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years))
- Overall Survival (OS) in Cohorts 1 to 8(Baseline until death (up to 6 years))
- PFS According to WHO Response Criteria in Cohorts 1 to 8(Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years))
- Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of R1507(Predose (0 hours [h]), end of 60-90 minutes infusion (EOI), postdose (2, 24, 72-96 h) in Week 1; predose (0 h) and EOI in Weeks 2, 4, 6, 9; predose (0 h), EOI, postdose (48 h) in Week 12; predose (0 h) in Week 13, at final visit (up to 6 years))
- Pharmacokinetics: Clearance (CL) of R1507(Predose (0 h), EOI (infusion over 60-90 minutes), postdose (2, 24, 72-96 h) in Week 1; predose (0 h) and EOI in Weeks 2, 4, 6, 9; predose (0 h), EOI, postdose (48 h) in Week 12; predose (0 h) in Week 13, at final visit (up to 6 years))