A Phase 1b/2, With Phase 2 Randomized, Study Evaluating the Efficacy of Doxorubicin With or Without a Human Anti-PDGFRα Monoclonal Antibody (IMC-3G3) in the Treatment of Advanced Soft Tissue Sarcoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 148
- 试验地点
- 1
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
The main purpose of this study is to gather information about the use of an investigational drug called olaratumab with a drug for soft tissue sarcoma called doxorubicin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant has histologically- or cytologically-confirmed malignant soft tissue sarcoma
- •The participant has advanced soft tissue sarcoma (STS), not amenable to treatment with surgery or radiotherapy
- •The participant's Eastern Cooperative Oncology Group (ECOG) performance status is 0-2
- •The participant has available tumor tissue from either the primary or metastatic tumor for determination of PDGFRα expression
- •The participant has adequate hematologic function as defined by an absolute neutrophil count (ANC) ≥ 1500 μL, hemoglobin ≥ 9.0 g/dL, and a platelet count of 100,000/μL obtained within 2 weeks prior to study entry
- •The participant has adequate hepatic function as defined by a total bilirubin ≤ 1.5 mg/dL, and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 times the upper limit of normal (ULN)
- •The participant has adequate renal function as defined by serum creatinine ≤ 1.5 × the institutional ULN. If creatinine is above the ULN, the participant's creatinine clearance is ≥ 45 mL/min
- •Because the teratogenicity of Olaratumab is not known, women of childbearing potential (WOCBP) and sexually active males must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
排除标准
- •The participant has histologically- or cytologically-confirmed Kaposi's sarcoma
- •The participant has untreated central nervous system metastases
- •The participant received prior treatment with doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones (ie, mitoxantrone)
- •The participant received prior radiation therapy to the mediastinal/pericardial area
- •The participant has a history of another primary cancer, with the exception of a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor treated with curative intent, no known active disease present, and no treatment administered during the last 3 years prior to study entry
- •The participant is receiving concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemo-embolization, targeted therapy, or an investigational agent
- •The participant has an elective or a planned major surgery to be performed during the course of the study
- •The participant has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, requiring parenteral antibiotics, symptomatic congestive heart failure, severe myocardial insufficiency, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •The participant has unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 6 months prior to study entry
- •The participant has known immunodeficiency virus (HIV) infection
- •The participant, if female, is pregnant or lactating
- •The participant has a known allergy to any of the treatment components
研究组 & 干预措施
Phase 1b: Olaratumab + doxorubicin
All cycles are 21 days.
Cycles 1-8: Olaratumab 15 mg/kg on days 1+8, and doxorubicin 75 mg/m2 on day 1
All subsequent cycles until progression: Olaratumab 15 mg/kg on days 1+8
干预措施: Olaratumab (Biological)
Phase 1b: Olaratumab + doxorubicin
All cycles are 21 days.
Cycles 1-8: Olaratumab 15 mg/kg on days 1+8, and doxorubicin 75 mg/m2 on day 1
All subsequent cycles until progression: Olaratumab 15 mg/kg on days 1+8
干预措施: doxorubicin (Drug)
Phase 2: Olaratumab and doxorubicin
All cycles are 21 days.
Cycles 1-8: Olaratumab 15 mg/kg on days 1+8, and doxorubicin 75 mg/m2 on day 1
All subsequent cycles until progression: Olaratumab 15 mg/kg on days 1+8
干预措施: Olaratumab (Biological)
Phase 2: Olaratumab and doxorubicin
All cycles are 21 days.
Cycles 1-8: Olaratumab 15 mg/kg on days 1+8, and doxorubicin 75 mg/m2 on day 1
All subsequent cycles until progression: Olaratumab 15 mg/kg on days 1+8
干预措施: doxorubicin (Drug)
Phase 2: Doxorubicin: Optional Olaratumab After Progression
All cycles are 21 days.
Cycles 1-8: doxorubicin 75 mg/m2 on day 1 until disease progression.
At disease progression: optional Olaratumab 15 mg/kg on days 1+8 until further progression.
干预措施: doxorubicin (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: Randomization Until the First Radiographic Documentation of Objective Progression (Up to 29 Months)
PFS is measured from randomization until the first radiographic documentation of progression of disease (PD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) or death from any cause. Participants who died without PD was considered to have progressed on the day of death. The following censoring rules applied: If no radiologic assessment at baseline or post baseline, participant was censored at the date of randomization. Participants were censored at the day of their last tumor assessment if no PD and were lost to follow up; If death or PD occurred after 2 or more consecutive missing radiographic visits, censoring occurred at the date of the last adequate radiographic visit. If participant started new treatment before PD, the participant was censored at the date of last tumor assessment prior to new therapy. If treatment was discontinued for reasons other than PD and no further assessment, censoring occurred at last tumor assessment.
Number of Participants With Treatment Related Adverse Events (TEAE), Adverse Events (AE) or Serious Adverse Events (SAE) for Safety for the Phase 1b Portion of the Study
时间窗: Baseline Up to 30 Months
All Phase 1b participants who experienced at least 1 TEAE in the Phase 1b portion of the study. Adverse Event with missing relationship to study is counted as related. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
次要结局
- Overall Survival (OS)(Randomization to the Date of Death From Any Cause (Up To 47 Months))
- Percentage of Participants With Objective Response (Objective Response Rate)(Randomization Until Progressive Disease (Up to 30 Months))
- Percentage of Participants Who Are Progression-Free (PFS) at 3 Months(Randomization Until First Radiographic PD or Death from Any Cause (Up to 3 Months))
- Number of Participants With AEs and SAEs for Phase 2 Portion(Baseline, Up to 30 Months)
- Pharmacokinetic (PK) Maximum Concentration (Cmax) Cycle 1 Day 1, Cycle 3 Day 1 of Olaratumab(Cycle 1 Day 1: Preinfusion, End of Infusion,1hr,48hr,72hr,168 hr Post infusion; Cycle 3 Day 1:Preinfusion, End of Infusion,1hr,24hr,48hr,72hr,168hr Post Infusion)
- PK: Minimum Concentration (Cmin) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab(Cycle 1 Day 8: Preinfusion, 1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr, 24hr,72hr,168hr Post Infusion)
- PK: Area Under Concentration Curve Versus Time (AUCτ) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab(Cycle 1 Day 8:Preinfusion,1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr,24hr,72hr,168hr Post Infusion)
- Percentage of Participants With Anti-Olaratumab Antibody Assessment(Baseline, Up to 30 Months)
- PK: Half-Life (T1/2) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab(Cycle 1 Day 8:Preinfusion,1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr,24hr,72hr,168hr Post Infusion)