An Open-Label Study to Evaluate the Pharmacokinetics of Doxorubicin Following the Concomitant Intravenous Administration of Olaratumab (IMC-3G3) to Patients With Advanced Soft Tissue Sarcoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 6
- 主要终点
- Pharmacokinetics (PK): Area Under The Concentration Curve Zero to Infinity (AUC[0-∞]) Doxorubicin
研究概览
简要总结
The purpose of this study is to assess how the body handles olaratumab when it is given with another drug called doxorubicin.
The safety and tolerability of these drugs will be studied. Each participant will complete two 21-day cycles in a fixed order. Participants who complete Cycle 2 may continue to receive olaratumab + doxorubicin for an additional six 21-day cycles and then may receive olaratumab alone until discontinuation criteria are met.
Screening is required within 21 days prior to first dose.
Part B was added in October, 2015 to assess how the body handles a higher dose of olaratumab when given with doxorubicin.
Participants may only enroll in one part.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 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 histological or cytological evidence of a diagnosis of soft tissue sarcoma (STS) that is advanced and/or metastatic
- •Have the presence of measurable and/or nonmeasurable disease
- •Have given written informed consent prior to any study-specific procedures
- •Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale
- •Have discontinued previous treatments for cancer and recovered from the acute effects of therapy
- •Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
排除标准
- •Have received treatment within 28 days of the initial dose of study drug with an investigational product or non-approved use of a drug or device for noncancer indications
- •Have received prior treatment with doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones
- •Have active central nervous system (CNS) metastasis. Participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids
- •Have unstable hepatic disease with a grade equal to or greater than Child-Pugh B
- •Have an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis
- •Have a history of another primary cancer, with the exception of a) curatively resected nonmelanoma 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
- •Have a history of chronic heart failure or left ventricular dysfunction
- •Have a resting heart rate of less than (<)50 beats per minute (bpm) or greater than (>)100 bpm
- •Have a history of radiation therapy involving the mediastinal/pericardial area. Previous radiation therapy is allowed but must not have included whole pelvis radiation
研究组 & 干预措施
Part A
Doxorubicin Alone: On Cycle 1, Day 1, participants received 75 milligram/square meter (mg/m2) of doxorubicin intravenously (IV).
Olaratumab Alone: On Cycle 1, Day 10, participants received 15 milligram/kilogram (mg/kg) of olaratumab IV.
Olaratumab + Doxorubicin: For Cycles 2 to 8, participants received 15 mg/kg of olaratumab on Days 1 and 8 of each 21-day cycle, IV and 75 mg/m2 of doxorubicin IV immediately following the completion of the olaratumab infusion.
Participants continued to receive olaratumab monotherapy (on days 1 and 8 of each cycle) for Cycle 9 onward, until discontinuation criteria are met.
干预措施: Olaratumab (Drug)
Part A
Doxorubicin Alone: On Cycle 1, Day 1, participants received 75 milligram/square meter (mg/m2) of doxorubicin intravenously (IV).
Olaratumab Alone: On Cycle 1, Day 10, participants received 15 milligram/kilogram (mg/kg) of olaratumab IV.
Olaratumab + Doxorubicin: For Cycles 2 to 8, participants received 15 mg/kg of olaratumab on Days 1 and 8 of each 21-day cycle, IV and 75 mg/m2 of doxorubicin IV immediately following the completion of the olaratumab infusion.
Participants continued to receive olaratumab monotherapy (on days 1 and 8 of each cycle) for Cycle 9 onward, until discontinuation criteria are met.
干预措施: Doxorubicin (Drug)
Part B
Doxorubicin Alone: On Cycle 1, Day 1, participants received doxorubicin 75 mg/m2 IV
Olaratumab Alone: On Cycle 1, Day 10, participants received 20 mg/kg of olaratumab IV.
Olaratumab + Doxorubicin:
For Cycle 2, participants received 20 mg of olaratumab on Days 1 and 8 of each 21-day cycle, IV. On Day 1 of Cycle 2, doxorubicin 75 mg/m2 was administered IV immediately following the completion of the olaratumab infusion.
For Cycles 3 - 8, Day 1 and 8, olaratumab 15 mg/kg was administered and on Day 1 doxorubicin 75 mg/m2 was administered IV immediately following the completion of the olaratumab infusion.
Participants continued to receive olaratumab monotherapy (on days 1 and 8 of each cycle) for Cycle 9 onwards, until discontinuation criteria are met.
干预措施: Olaratumab (Drug)
Part B
Doxorubicin Alone: On Cycle 1, Day 1, participants received doxorubicin 75 mg/m2 IV
Olaratumab Alone: On Cycle 1, Day 10, participants received 20 mg/kg of olaratumab IV.
Olaratumab + Doxorubicin:
For Cycle 2, participants received 20 mg of olaratumab on Days 1 and 8 of each 21-day cycle, IV. On Day 1 of Cycle 2, doxorubicin 75 mg/m2 was administered IV immediately following the completion of the olaratumab infusion.
For Cycles 3 - 8, Day 1 and 8, olaratumab 15 mg/kg was administered and on Day 1 doxorubicin 75 mg/m2 was administered IV immediately following the completion of the olaratumab infusion.
Participants continued to receive olaratumab monotherapy (on days 1 and 8 of each cycle) for Cycle 9 onwards, until discontinuation criteria are met.
干预措施: Doxorubicin (Drug)
结局指标
主要结局
Pharmacokinetics (PK): Area Under The Concentration Curve Zero to Infinity (AUC[0-∞]) Doxorubicin
时间窗: Cycle(C)1 and (C)2, Day(D)1: Predose, 0.5, 1, 2, 4, 8, 24, 48, 72, 96 Hours (Hrs) Post dose
PK: Maximum Concentration (Cmax) Doxorubicin
时间窗: C1 and C2, D1: Predose, 0.5, 1, 2, 4, 8, 24, 48, 72, 96 Hrs Post dose
次要结局
- PK:Time of Maximum Observed Concentration (Tmax) Doxorubicin(C1 and C2, D1: Predose, 0.5, 1, 2, 4, 8, 24, 48, 72, 96 Hrs Post dose)
- PK: AUC Zero to Time t, Where t is the Last Time Point (0-tLast) Olaratumab(C1 D10: Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose; C2 D1: Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose)
- PK: Cmax Olaratumab(C1 D10:Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose; C2 D1: Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose)
- PK: Tmax Olaratumab(C1 D10: Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose; C2 D1: Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose)
- Percentage of Participants With Olaratumab Antibodies(Preinfusion on Day 1 of Cycles 1 through 3 and Preinfusion on Day 1 of Every Second Cycle Thereafter, Up to 30-Day Follow Up)
- Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)](Baseline to Measured Progressive Disease, Study Discontinuation or Death (Up to 24 Months))