Dose Finding and Randomized, Multicenter, Placebo-Controlled, Phase 2 Study of Enzastaurin and Sunitinib Versus Placebo and Sunitinib in Patients With Metastatic Renal Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Progression Free Survival (PFS) in Part 2
研究概览
简要总结
This study will compare the effects of Enzastaurin plus Sunitinib versus Sunitinib alone in metastatic Renal Cell Cancer.
详细描述
This is a multicenter, Phase 2 study of enzastaurin and sunitinib versus placebo and sunitinib as first-line therapy in participants with metastatic renal cell carcinoma, containing 2 parts. Part 1 is a safety lead-in study with 12 participants and possible dose escalation. Part 2 is a randomized, double-blind, Phase 2 study in 110 participants.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Participants with metastatic Renal Cell Carcinoma (RCC) who have not received prior treatment with systemic (adjuvant or neoadjuvant) therapy for RCC (including targeted therapy such as tyrosine kinase inhibitors or bevacizumab, immunotherapy, chemotherapy, hormonal, or investigational therapy)
- •Histologically confirmed RCC with metastases with a component of clear (conventional) cell histology
- •Evidence of unidimensional measurable disease, measured by computed tomography (CT) scan or magnetic resonance imaging (MRI)
- •Primary tumor has been surgically removed by nephrectomy or nephron-sparing surgery
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- •Participants must sign an informed consent document
排除标准
- •Have received prior treatment with sunitinib or enzastaurin
- •Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry
- •Have had any of the following within 12 months prior to study drug administration:
- •myocardial infarction,
- •severe/unstable angina,
- •coronary/peripheral artery bypass graft,
- •symptomatic congestive heart failure (CHF),
- •cerebrovascular accident,
- •transient ischemic attack, or
- •pulmonary embolism
- •Note: Ongoing treatment with therapeutic doses of Coumadin® (warfarin) or a derivative of Coumadin or phenprocoumon is not allowed, but prophylactic, low-dose Coumadin (≤ 2 mg daily) for deep vein thrombosis is allowed. In such cases, prothrombin time/international normalization ratio (PT/INR) should be very closely monitored as clinically indicated
- •Ongoing cardiac arrhythmias >New York Health Association Class II, atrial fibrillation of any grade, or prolongation of the QTc interval to >450 millisecond (msec) for males or >470 msec for females.
- •Have uncontrolled hypertension [>150/100 millimeter of mercury (mm/Hg) despite optimal medical therapy], or history of poor compliance with antihypertensive treatment
- •Require concomitant use of potent Cytochrome P450 3A4 (CYP3A4) inducer, for example, rifampicin or potent CYP3A inhibitors, such as ketoconazole.
- •Significant surgery or radiation therapy <4 weeks of starting study treatment. Prior palliative radiotherapy to metastatic lesion(s) is/are permitted, provided there is at least 1 measurable lesion that has not been irradiated
- •Participants who are pregnant or breast feeding
研究组 & 干预措施
Part 1 Arm A: Enzastaurin + Sunitinib
(Cohort 1): On cycle 1, day 1 a loading dose 125 milligram (mg) of Enzastaurin was administered by mouth orally, (BID) twice a day, followed by Enzastaurin 125 mg administered, twice a day, Days 2 through 42 of a 6-week cycle.
(Cohort 2): Cycle 1, Day 1 loading dose 375 mg of Enzastaurin administered po three times a day (TID), followed by 250 mg, po, BID continuously until disease progression, unacceptable toxicity, death, or discontinuation from the study for any other reason.
Sunitinib 50 mg was administered orally, once daily, Days 1-28, then rest (no drug given) days 29-42.
Phase 2 (Part 2): Randomized Double-Blind: Dosing was determined by Part 1. Part 2 was not activated per recommendation of safety review committee.
Enzastaurin: Cycle 1, Day 1 loading dose 375 mg administered orally, (TID) three times a day, followed by Part 1 dose twice a day on Days 2-42 of 6 week cycle.
Sunitinib: 50 mg administered orally, once daily, on Days 1-28, then rest Days 29-42.
干预措施: Enzastaurin (Drug)
Part 1 Arm A: Enzastaurin + Sunitinib
(Cohort 1): On cycle 1, day 1 a loading dose 125 milligram (mg) of Enzastaurin was administered by mouth orally, (BID) twice a day, followed by Enzastaurin 125 mg administered, twice a day, Days 2 through 42 of a 6-week cycle.
(Cohort 2): Cycle 1, Day 1 loading dose 375 mg of Enzastaurin administered po three times a day (TID), followed by 250 mg, po, BID continuously until disease progression, unacceptable toxicity, death, or discontinuation from the study for any other reason.
Sunitinib 50 mg was administered orally, once daily, Days 1-28, then rest (no drug given) days 29-42.
Phase 2 (Part 2): Randomized Double-Blind: Dosing was determined by Part 1. Part 2 was not activated per recommendation of safety review committee.
Enzastaurin: Cycle 1, Day 1 loading dose 375 mg administered orally, (TID) three times a day, followed by Part 1 dose twice a day on Days 2-42 of 6 week cycle.
Sunitinib: 50 mg administered orally, once daily, on Days 1-28, then rest Days 29-42.
干预措施: Sunitinib (Drug)
Part 2 Arm B: Sunitinib + Placebo
Part 2 was not activated per recommendation of safety review committee.
Sunitinib: 50 mg administered orally, once daily, Day 1-28, then rest Days 29-42.
Placebo: Cycle 1 Day 1 loading dose 3 tablets on Day 1, then 2 tablets daily, days 2-42.
干预措施: Sunitinib (Drug)
Part 2 Arm B: Sunitinib + Placebo
Part 2 was not activated per recommendation of safety review committee.
Sunitinib: 50 mg administered orally, once daily, Day 1-28, then rest Days 29-42.
Placebo: Cycle 1 Day 1 loading dose 3 tablets on Day 1, then 2 tablets daily, days 2-42.
干预措施: Placebo (Drug)
结局指标
主要结局
Progression Free Survival (PFS) in Part 2
时间窗: Randomization to Measured Progressive Disease (PD) (Up to 24 Months)
Progression-free survival (PFS) was defined as the number of months between the date of randomization and the date of first documented disease progression or the date of death due to any cause, whichever came first.
次要结局
- Number of Participants With Adverse Events (AEs) or Serious AEs (SAEs) in Part 1(Randomization to Study Completion (Up to 6 Cycles))
- Overall Survival (OS) in Part 2(Randomization to Death from Any Cause (Up to 24 Months))
- Pharmacokinetics (PK): Area Under Concentration Time Curve During One Dosing Interval at Steady State (AUCτ,ss) of Enzastaurin + Metabolite (LSN326020) + Total Analytes in Part 1(Cycle 1 Day 15: Predose, 2, 4, and 6 - 8 hours, Up to 12 Hours Post dose)
- Time-To-Tumor Progression in Part 2(Randomization to the Date of Objective Progressive Disease or Date of Death due to Study Disease, whichever came first (Up to 24 Months))
- PK: Maximum Concentration at Steady State (Cmax,ss) of Enzastaurin + LSN326020 + Total Analytes in Part 1(Cycle 1 Day 15: Predose, 2, 4, and 6 - 8 hours, Up to 12 Hours Post dose)