A Phase 1b/Adaptive Phase 2 Study of Docetaxel With or Without MLN1117 in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 14
- 主要终点
- Maximum Tolerated Dose (MTD) of TAK-117 in Combination With Docetaxel 36 mg/m^2 in Phase 1b
研究概览
简要总结
The purpose of this study is to determine the recommended phase 2 dose (RP2D) of TAK-117 when administered in combination with docetaxel in participants with non-small cell lung cancer (NSCLC) and to evaluate efficacy, safety, and tolerability of TAK-117 administered alone and in combination with docetaxel at the RP2D in participants with locally advanced or metastatic non-small cell lung cancer.
详细描述
The drug being evaluated in this study is called TAK-117. TAK-117 is tested in combination with docetaxel versus docetaxel alone for the treatment of non-small cell lung cancer (NSCLC).
This study consisted of 2 phases:
- Phase 1b - dose escalation phase
- Phase 2 - expansion phase.
The study enrolled 14 patients with NSCLC who have been treated with multiple prior lines of therapies will be enrolled for Phase 1b. The participants will receive docetaxel (36 mg/m^2) intravenous (IV) and TAK-117 tablets, orally administered, once daily in 21-day dosing cycles. The TAK-117 dose will be escalated until recommended Phase 2 dose (RP2D) is determined.
Each part of the adaptive Phase 2 portion of the study is designed as a stand-alone, randomized study evaluating PFS as the primary efficacy measure in a total of 60 participants between the 2 treatment arms: TAK-117 plus docetaxel versus docetaxel alone. An event-driven analysis of PFS will be performed after each part of Phase 2. On the basis of the PFS analysis of the preceding part of the study, the study may be stopped for efficacy or futility, or proceed to the next part. However, Phase 2 of the study was cancelled.
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
- 未提供
排除标准
- •Previous treatment with a PI3K or AKT inhibitor.
- •Prior cancer therapy or other investigational therapy within 2 weeks before the first administration of study drug or failed to recover from the reversible effects of prior anticancer therapies. For prior therapies with a half-life longer than 3 days, the interval must be at least 28 days before the first administration of study drug, and the participant must have documented progressive disease.
- •Has poorly controlled diabetes mellitus defined as HbA1c > 6.5%.
- •Has taken strong inhibitors or strong inducers of CYP3A4 within 14 days before the first dose of study drug.
- •Has taken histamine-H2 receptor antagonists and/or neutralizing antacids within 24 hours before the first administration of study drug.
- •Has taken proton pump inhibitors within 7 days before the first administration of study drug.
- •Has a condition that requires the concomitant use of any of the protocol-excluded medications, supplements, or food products during the course of the study .
- •Has any clinically significant co-morbidities.
- •Has acute myocardial infarction within 6 months before starting study drug, current or history of New York Heart Association Class III or IV heart failure; evidence of current uncontrolled cardiovascular conditions including cardiac arrhythmias, angina, pulmonary hypertension, or electrocardiogram (ECG) evidence of acute ischemia or active conduction system abnormalities; Fridericia's corrected QT interval > 475 milliseconds (msec) (males) or > 450 msec (females) on a 12-lead ECG during the Screening period; or abnormalities on 12-lead ECG including, but not limited to, changes in rhythm and intervals that in the opinion of the investigator are considered to be clinically significant.
- •Has known, previously diagnosed human immunodeficiency virus infection or active chronic hepatitis B or C.
- •Has brain metastasis, unless has completed definitive therapy, is not on steroids, has a stable neurologic status for at least 2 weeks after completion of the definitive therapy and steroids, and does not have neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- •Has active secondary malignancy that requires treatment.
- •Has any serious medical or psychiatric illness, including drug or alcohol abuse.
- •Male participants who intend to donate sperm during the course of this study or 120 days after receiving their last dose of TAK-117 and, for docetaxel, for as long as is mandated by local labeling.
- •Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before administration of the first dose of study drug.
- •Is unwilling or unable to abide by the requirements of the study.
研究组 & 干预措施
TAK-117 200 mg + Docetaxel (36 mg/m^2)
TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up ro Cycle 9 (approximately 189 days).
干预措施: Docetaxel (Drug)
TAK-117 200 mg + Docetaxel (36 mg/m^2)
TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up ro Cycle 9 (approximately 189 days).
干预措施: TAK-117 (Drug)
TAK-117 300 mg + Docetaxel 36 mg/m^2
TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days).
干预措施: Docetaxel (Drug)
TAK-117 300 mg + Docetaxel 36 mg/m^2
TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days).
干预措施: TAK-117 (Drug)
Phase 2 - TAK-117 + Docetaxel 36 mg/m^2
TAK-117 tablets, at the dose determined in the dose escalation phase, on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of a 21-day cycle plus Docetaxel 36 mg/m^2 IV infusion on Days 1 and 8 of a 21-day cycle.
干预措施: Docetaxel (Drug)
Phase 2 - TAK-117 + Docetaxel 36 mg/m^2
TAK-117 tablets, at the dose determined in the dose escalation phase, on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of a 21-day cycle plus Docetaxel 36 mg/m^2 IV infusion on Days 1 and 8 of a 21-day cycle.
干预措施: TAK-117 (Drug)
Phase 2 - Docetaxel 75 mg/m^2
Docetaxel 75 mg/m^2, IV infusion once every 3 weeks (per approved prescribing information) with dosing on Day 1 of each 21-day cycle.
干预措施: Docetaxel (Drug)
Phase 2 - Docetaxel 75 mg/m^2
Docetaxel 75 mg/m^2, IV infusion once every 3 weeks (per approved prescribing information) with dosing on Day 1 of each 21-day cycle.
干预措施: TAK-117 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of TAK-117 in Combination With Docetaxel 36 mg/m^2 in Phase 1b
时间窗: Cycle 1 (Up to Day 21)
The MTD is defined as the dose of TAK-117 in combination with docetaxel 36 mg/m\^2 at which 1 of 6 evaluable participants experience DLT. DLT was evaluated according to NCI CTCAE version 4.03 and was defined as any of the following events: 1. Grade 4 neutropenia or thrombocytopenia lasting ≥7 consecutive days; 2. Grade 4 neutropenia with fever and/or infection; 3. Platelet count \<10,000/mm\^3; 4. ≥Grade 3 thrombocytopenia with bleeding; 5. Any other ≥Grade 4 hematologic toxicity; 6. Any other ≥Grade 3 nonhematologic toxicity, with following exceptions: ≥Grade 3 arthralgia/myalgia, ≥Grade 3 nausea/emesis, ≥Grade 3 diarrhoea, Grade 3 fatigue, Grade 3 Rash, Grade 3 nonhematological toxicity that could be controlled to ≤Grade 1 with appropriate treatment; 7. Inability to administer at least 75% of planned doses; 8. Clinically significant occurrence per investigator that is a safety risk.
Recommended Phase 2 Dose of TAK-117 in Phase 1b
时间窗: Cycle 1 (Up to Day 21)
The recommended phase 2 dose was determined in Phase 1b based on participant dose-limiting toxicities and the maximum tolerated dose.
Progression-Free Survival (PFS) in Phase 2
时间窗: Approximately 12 months in Phase 2
PFS is defined as the time from the date randomization to the date of first documented progressive disease (PD) or death as assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease.
Number of Participants With Dose-Limiting Toxicity (DLT) in Phase 1b
时间窗: Cycle 1 (Up to Day 21)
DLT was evaluated according to National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 and was defined as any of the following events: 1. Grade 4 neutropenia or thrombocytopenia lasting ≥7 consecutive days; 2. Grade 4 neutropenia with fever and/or infection; 3. Platelet count \<10,000/mm\^3; 4. ≥Grade 3 thrombocytopenia with bleeding; 5. Any other ≥Grade 4 hematologic toxicity; 6. Any other ≥Grade 3 nonhematologic toxicity, with following exceptions: ≥Grade 3 arthralgia/myalgia, ≥Grade 3 nausea/emesis, ≥Grade 3 diarrhoea, Grade 3 fatigue, Grade 3 Rash, Grade 3 nonhematological toxicity that could be controlled to ≤Grade 1 with appropriate treatment; 7. Inability to administer at least 75% of planned doses; 8. Clinically significant occurrence per investigator that is a safety risk.
次要结局
- Overall Survival (OS) in Phase 2(Approximately 12 months in Phase 2)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Phase 1b(From first dose of study drug to 30 days after last dose of study drug (Up to Day 223))
- Response Rate in Phase 2(Approximately 12 months in Phase 2)
- Number of Participants With Significant Change in Physical Examination Reported as Adverse Events in Phase 2(Approximately 12 months in Phase 2)
- Disease Control Rate in Phase 2(Approximately 12 months in Phase 2)
- TAK-117 Plasma Concentration in Phase 1b(Cycle 1 Day 1 pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose)
- Number of Participants With Significant Change in Physical Examination Reported as Adverse Events in Phase 1b(First dose of study drug through 30 days after the last dose of study drug (Up to Day 223))
- TAK-117 Plasma Concentrations When Administered 1 Day After Docetaxel in Phase 2(1 day post docetaxel dose)
- Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 2(Approximately 12 months in Phase 2)
- Number of Participants With Significant Change in Vital Signs Reported as Adverse Events in Phase 1b(First dose of study drug through 30 days after the last dose of study drug (Up to Day 223))
- Number of Participants With Electrocardiogram (ECG) Findings Reported as Adverse Events in Phase 1b(First dose of study drug through 30 days after the last dose of study drug (Up to Day 223))
- Number of Participants With Significant Change in Vital Signs Reported as Adverse Events in Phase 2(Approximately 12 months in Phase 2)
- Time to Progression in Phase 2(Approximately 12 months in Phase 2)
- Cmax: Maximum Observed Plasma Concentration for TAK-117(Cycle 1 Day 1 pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose)
- AUCtau: Area Under the Concentration Time Curve From Time 0 to the Next Dose in Phase 1b for TAK-117(Cycle 1 Day 1 pre-dose and up to 24 hours post-dose)
- AUC(Last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration in Phase 1b for TAK-117(Cycle 1 Day 1 pre-dose and up to 24 hours post-dose)
- Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b(First dose of study drug through 30 days after the last dose of study drug (Up to Day 223))
- Duration of Response in Phase 2(Approximately 12 months in Phase 2)
- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-117(Cycle 1 Day 1 pre-dose and up to 24 hours post-dose)
- Number of Participants With Electrocardiogram (ECG) Findings Reported as Adverse Events in Phase 2(Approximately 12 months in Phase 2)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Phase 2(Approximately 12 months in Phase 2)
- CL/F: Oral Clearance for TAK-117(Cycle 1 Day 1 pre-dose and up to 24 hours post-dose)
- T1/2: Terminal Phase Elimination Half-life (T1/2) for TAK-117(Cycle 1 Day 1 pre-dose and up to 24 hours post-dose)