A Phase 1, Pharmacologic and Pharmacodynamic Study of MM-121 in Combination With Multiple Anticancer Therapies in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 43
- 主要终点
- To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Pemetrexed
研究概览
简要总结
To evaluate the safety and tolerability of escalating doses of MM-121 + certain anticancer therapies
详细描述
This study was a Phase 1 and pharmacologic dose-escalation trial of MM-121 in combination with certain anticancer therapies. The dose-escalation portion of the study employed a 3 + 3 design to assess the safety, tolerability, and pharmacokinetics of MM-121 administered weekly in combination with certain anticancer therapies in patients with advanced/recurrent cancer. Doses of MM-121 and/or the anticancer therapy were escalated until either the MTD is identified or the combination was shown to be tolerable at the highest planned doses.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Advanced-stage solid tumors
- •≥ 18 years of age
- •Adequate liver and kidney function
排除标准
- •Any other active malignancy
- •No known HIV, Hepatitis C or B
研究组 & 干预措施
MM-121 plus Gemcitabine
escalating doses of MM-121 and gemcitabine on Day 1 and Day 8 of every 3 week cycle
干预措施: MM-121 (Drug)
MM-121 plus Gemcitabine
escalating doses of MM-121 and gemcitabine on Day 1 and Day 8 of every 3 week cycle
干预措施: Gemcitabine (Drug)
MM-121 plus Carboplatin
carboplatin at AUC 6 with escalating doses of MM-121 on Day 1 of every 3 week cycle
干预措施: MM-121 (Drug)
MM-121 plus Carboplatin
carboplatin at AUC 6 with escalating doses of MM-121 on Day 1 of every 3 week cycle
干预措施: Carboplatin (Drug)
MM-121 plus Pemetrexed
pemetrexed at 500 mg/m2 with escalating doses of MM-121 on Day 1 of every 3 week cycle
干预措施: MM-121 (Drug)
MM-121 plus Pemetrexed
pemetrexed at 500 mg/m2 with escalating doses of MM-121 on Day 1 of every 3 week cycle
干预措施: Pemetrexed (Drug)
MM-121 plus Cabazitaxel
escalating doses of MM-121 and cabazitaxel on Day 1 of every 3 week cycle
干预措施: MM-121 (Drug)
MM-121 plus Cabazitaxel
escalating doses of MM-121 and cabazitaxel on Day 1 of every 3 week cycle
干预措施: Cabazitaxel (Drug)
结局指标
主要结局
To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Pemetrexed
时间窗: From date of first dose to 30 days after termination, the longest 88.1 weeks
Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Pemetrexed doses tested: 500 mg/m2 Day 1
To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Cabazitaxel
时间窗: From date of first dose to 30 days after termination, the longest 88.1 weeks
Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Cabazitaxel doses tested: 20 or 25 mg/m2 Day 1 of 3
To Characterize Dose-limiting Toxicities (DLTs) Associated With the Combination of MM-121 With Anticancer Therapies
时间窗: From date of first dose to 30 days after termination, the longest 88.1 weeks
To establish the safety of escalating doses of MM-121 administered in combination with multiple anti-cancer therapies in order to determine the recommended phase 2 dose. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD to be used for the expansion cohort. DLTs were not measured in the Expansion Cohort.
To Evaluate the Safety and Tolerability of Escalating Doses of the MM-121 Anticancer Therapies
时间窗: From date of first dose to 30 days after termination, the longest 88.1 weeks
Safety and tolerability data presented in detail in the adverse events and serious adverse events section of the results posting
To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: MM-121 Doses
时间窗: From date of first dose to 30 days after termination, the longest 88.1 weeks
Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Gemcitabine doses tested: 1000 mg/m2 Day 1 and 8 Pemetrexed doses tested: 500 mg/m2 Day 1 Carboplatin doses tested: 5 or 6 AUC Day 1 Cabazitaxel doses tested: 20 or 25 mg/m2 Day 1 of 3
To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Gemcitabine
时间窗: From date of first dose to 30 days after termination, the longest 88.1 weeks
Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Gemcitabine doses tested: 1000 mg/m2 Day 1 and 8
To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Carboplatin
时间窗: From date of first dose to 30 days after termination, the longest 88.1 weeks
Maximum Tolerated Dose reported in Target AUC, as calculated by the Calvert Formula Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose. Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Carboplatin doses tested: 5 or 6 AUC Day 1
次要结局
- Objective Response Rate(patients were assessed for response during their time on study, the longest of which was 88.1 weeks)
- Pharmacokinetics(Collections taken at Cycle 1, Week 1 for all patients at start of the infusion (pretreatment), at the end of the infusion, and at 2, 4, 24 and 48 hours after the start of the MM-121 infusion)
- Pharmacokinetics (AUClast)(Collections taken at Cycle 1, Week 1 for all patients at the start of the infusion (pretreatment), at the end of the infusion, and at 2, 4, 24 and 48 hours after the start of the MM-121 infusion)
- Immunogenicity(Samples were collected for all patients pre-dose on all cycles for duration of treatment, the longest of which was 88.1 weeks, and a collection was made post-infusion in any case of infusion reaction)