NCT01862328已完成1 期
A Phase 1b, Open-Label, Dose Escalation, Multi-arm Study of MLN4924 Plus Docetaxel, Gemcitabine, or Combination of Carboplatin and Paclitaxel in Patients With Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 64
- 主要终点
- Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The purpose of this study is to establish the maximum tolerated dose (MTD) and assess the safety and tolerability of MLN4924 (pevonedistat) in combination with docetaxel, paclitaxel and carboplatin, and gemcitabine in participants with solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 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
- •18 years of age or older
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
- •Have a histologically or cytologically confirmed metastatic or locally advanced and incurable solid tumor that is felt to be appropriate for treatment with 1 of the 3 chemotherapy regimens in this study, or have progressed despite standard therapy, or for whom conventional therapy is not considered effective. The tumor must be radiographically or clinically evaluable and/or measurable
- •Recovered (that is, <=Grade 1 toxicity) from the effects of prior antineoplastic therapy
- •Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence
- •Male participants who agree to practice effective barrier contraception or agree to practice true abstinence
- •Voluntary written consent must be given before performance of any study-related procedure
- •Suitable venous access for the study-required blood sampling
- •Adequate clinical laboratory values during the screening period as specified in the protocol
- •Participants who are willing to refrain from donating blood for at least 90 days after their final dose of MLN4924 and (for male participants) willing to refrain from donating semen for at least 4 months after their final dose of MLN4924
- •Availability of fixed tumor specimen (block or slides) for exploratory biomarker analysis. If no slides or block are available, fresh tumor biopsies should be obtained and used for these assessments
排除标准
- •Major surgery within 14 days before the first dose of study drug
- •Female participants who are lactating or pregnant
- •Active uncontrolled infection or severe infectious disease
- •Receiving antibiotic therapy within 14 days before the first dose of study treatment
- •Life-threatening illness unrelated to cancer
- •Known hypersensitivity to study-assigned chemotherapy
- •Prior treatment with MLN4924; however, prior treatment with docetaxel, paclitaxel,carboplatin, and gemcitabine is allowed
- •History of severe hypersensitivity reactions to docetaxel (polysorbate 80-based formulations) for participants to be enrolled in Arm 1 (MLN4924 + docetaxel), history of hypersensitivity to carboplatin for participants to be enrolled in Arm 2 (MLN4924 + paclitaxel + carboplatin), or history of severe hypersensitivity to paclitaxel (cremophor-based formulations) for participants to be enrolled in Arm 2
- •Persistent diarrhea (greater than Grade 2) lasting >3 days within 2 weeks before the first dose of study treatment
- •Systemic antineoplastic therapy within 21 days before the first dose of study drug
- •Radiotherapy within 14 days preceding the first dose of study treatment
- •Prior treatment with radiation therapy involving greater than or equal to (>=) 25% of the hematopoietically active bone marrow
- •Treatment with cytochrome P450 3A (CYP3A) inducers within 14 days before the first dose of MLN
- •Treatment with CYP3A inhibitors within 14 days before the first dose of MLN4924; however, voriconazole and fluconazole need only be stopped for 3 days before MLN
- •Participants must have no history of amiodarone use in the 6 months before the first dose of MLN4924
- •Clinically uncontrolled central nervous system (CNS) involvement
- •Any serious medical or psychiatric illness
- •Treatment with any investigational products 21 days prior to treatment
- •Unwilling or unable to refrain from using statins 24 hours before, the day of, and 24 hours after each MLN4924 administration
- •Known human immunodeficiency virus (HIV) positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
- •Known hepatic cirrhosis
- •Known cardiac/cardiopulmonary disease
- •Left ventricular ejection fraction
- •with a cardiac pacer whose heart rate is set at a fixed rate and participants on concomitant medication that may limit increase in heart rate in response to hypotension 24 History of severe intolerance to cytotoxic agent(s) given in the assigned arm
研究组 & 干预措施
MLN4924 + Paclitaxel + Carboplatin (Arm 2)
Experimental
干预措施: Carboplatin (Drug)
MLN4924 and Docetaxel (Arm 1)
Experimental
干预措施: MLN4924 (Drug)
MLN4924 and Docetaxel (Arm 1)
Experimental
干预措施: Docetaxel (Drug)
MLN4924 + Paclitaxel + Carboplatin (Arm 2)
Experimental
干预措施: MLN4924 (Drug)
MLN4924 + Paclitaxel + Carboplatin (Arm 2)
Experimental
干预措施: Paclitaxel (Drug)
MLN4924 + Gemcitabine (Arm 3)
Experimental
干预措施: MLN4924 (Drug)
MLN4924 + Gemcitabine (Arm 3)
Experimental
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: Baseline up to 30 days after the last dose of study drug (up to 5 years)
Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings
时间窗: Baseline up to 30 days after the last dose of study drug (up to 5 years)
Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings
时间窗: Baseline up to 30 days after the last dose of study drug (up to 5 years)
次要结局
- Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924(Cycle 1 Day 1 pre-dose and at multiple time points (up to 20 hours) post-dose (Cycle Length=21 days [Arm 1 and 2] and 28 days [Arm 3]))
- MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924(Cycle 1 Days 1 and 5 pre-dose and at multiple time points (up to 20 hours) post-dose (Cycle Length=21 days [Arm 1 and 2]))
- Percentage of Participants With Objective Response(Screening, Cycle 2 Days 15 (Arm 1, 2a, and 2) and 22 (Arm 3) then every other Cycle thereafter up to 30 days after the last dose of study drug (up to 5 years) (Cycle Length = 21 days [Arm 1, 2a, and 2] and 28 days [Arm 3]))
- Duration of Response(From the date of first documented response (CR or PR) to the date of first documented PD or the date of last disease assessment if the participants discontinued the study before PD (up to 5 years))
研究者
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