A Phase 1b Trial to Assess the Modulation of Biological Markers in Patients With Potentially Resectable Soft Tissue Sarcoma Treated With Olaratumab Monotherapy Followed by Olaratumab Plus Doxorubicin Combination Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 10
- 主要终点
- Percent Change From Baseline in Enumeration of Circulating Tumor Cells (CTCs) in Whole Blood
研究概览
简要总结
The purpose of this study is to evaluate potential biomarkers and method of action, efficacy and safety of olaratumab in participants with soft tissue sarcoma (STS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Have a histologically confirmed diagnosis of STS for which olaratumab and doxorubicin would be appropriate therapy. Participants with a diagnosis of Grade 1 liposarcoma are eligible if there is histological or radiographic evidence of evolution to more aggressive disease. Participants with Kaposi's sarcoma and gastrointestinal stromal tumors (GIST) will be excluded. Participants must have potentially resectable disease (as assessed by the study investigator) and have a primary tumor lesion deemed amenable to serial biopsy.
- •For radiotherapy addendum only: Have a histologically confirmed diagnosis of STS of the extremities, Grade 2 or 3, >5 centimeters, for which olaratumab and radiotherapy would be appropriate therapy. Participants with Kaposi's sarcoma, GIST or myxoid liposarcoma will be excluded.
- •Have consented to undergo mandatory serial peripheral whole blood and tumor tissue sampling.
排除标准
- •Have active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of enrollment. Participants with a history of a CNS metastasis previously treated with curative intent (for example, stereotactic radiation or surgery) that have not progressed on follow-up imaging, have been asymptomatic for at least 60 days and are not receiving systemic corticosteroids and or/anticonvulsants, are eligible. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before enrollment to rule out brain metastasis.
- •Have received prior treatment with doxorubicin, epirubicin, idarubicin, and/or other anthracyclines or anthracenediones; the participant has received treatment with olaratumab or has participated in a prior olaratumab trial.
- •For radiotherapy addendum only: Have received previous radiotherapy in the primary tumor lesion and/or prior treatment with olaratumab or has participated in a prior olaratumab trial.
研究组 & 干预措施
Olaratumab + Doxorubicin
Cycle 1: Olaratumab 20 milligram per kilogram (mg/kg) given intravenously (IV) on Day 1 and Day 8 (21 day cycle).
Cycle 2: Olaratumab 20 mg/kg given IV on Day 1 and Day 8 plus doxorubicin 75 mg/m2 given IV on Day 1 (21 day cycle).
Cycle 3 through Cycle 7: Olaratumab 15 mg/kg given IV on Day 1 and Day 8 plus doxorubicin 75 mg/m2 given IV on Day 1 (21 day cycles).
干预措施: Olaratumab (Drug)
Olaratumab + Doxorubicin
Cycle 1: Olaratumab 20 milligram per kilogram (mg/kg) given intravenously (IV) on Day 1 and Day 8 (21 day cycle).
Cycle 2: Olaratumab 20 mg/kg given IV on Day 1 and Day 8 plus doxorubicin 75 mg/m2 given IV on Day 1 (21 day cycle).
Cycle 3 through Cycle 7: Olaratumab 15 mg/kg given IV on Day 1 and Day 8 plus doxorubicin 75 mg/m2 given IV on Day 1 (21 day cycles).
干预措施: Doxorubicin (Drug)
Olaratumab + Radiotherapy Addendum
Olaratumab given IV on Day 1 and Day 8 (21 day cycle) concurrently with radiotherapy.
Radiotherapy addendum was not implemented.
干预措施: Olaratumab (Drug)
Olaratumab + Radiotherapy Addendum
Olaratumab given IV on Day 1 and Day 8 (21 day cycle) concurrently with radiotherapy.
Radiotherapy addendum was not implemented.
干预措施: External Beam Radiotherapy (Radiation)
结局指标
主要结局
Percent Change From Baseline in Enumeration of Circulating Tumor Cells (CTCs) in Whole Blood
时间窗: Baseline, End of Cycle 1 (21 days)
Enumeration of CTCs pre- and post- treatment with olaratumab may be a useful biomarker given the predilection for sarcomas to spread hematogenously.
Percent Change From Baseline in Gene Expression of Platelet-Derived Growth Factor Receptor Alpha (PGDFRα) and PGDFR Beta (β) in Tumor Tissue
时间窗: Baseline, End of Cycle 1 (21 days)
Over-activity of PDGF signaling is associated with the development of certain malignant diseases. Olaratumab is an IgG1 antagonist of PDGFRα.
Percent Change From Baseline in Gene Expression of PDGF A, PDGF B, PDGF C, and PDGF-D Canonical Ligands in Tumor Tissue
时间窗: Baseline, End of Cycle 1 (21 days)
PDGF A, PDGF B, PDGF C, and PDGF D are platelet-derived growth factor canonical ligands associated with activation of PDGFR α and β.
次要结局
- Percentage of Participants With Resectable Tumors (Resectability Rate)(Cycle 1 through Cycle 7 (Up to 6 Months))
- Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Monotherapy(Cycle 1 Days 1 and 8: Predose; 5 minutes(m) post-infusion)
- Progression Free Survival (PFS)(Baseline to Objective Progression or Death from Any Cause (Up to 18 Months))
- Objective Response Rate (ORR): Percent of Participants With Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR)(Baseline to Measured Progressive Disease (Up to 18 Months))
- Disease Control Rate (DCR): Percent of Participants Who Exhibit Stable Disease (SD), CR or PR(Baseline to Measured Progressive Disease (Up to 18 Months))
- Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab(Cycle 2 Day 1: Predose, 5 minutes(m) post-infusion, 24 hours(h), 96h; Day 8:Predose, 5 m, and 24h, 48h, 96h, and 240h postdose; Cycle 3 Day 1 and Day 8: Predose and 5m post-infusion)
- Number of Participants With Anti-Olaratumab Antibodies(Predose Cycle 1 Day 1 through Follow-Up (Up to 8 Months))