A Phase 2 Study of MLN8237, a Novel Aurora A Kinase Inhibitor, in the Treatment of Patients With Platinum-Refractory or Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Combined Best Overall Response Rate Based on Investigator Assessment
研究概览
简要总结
The purpose of this study is to evaluate the anti-tumour activity of alisertib (MLN8237) in the treatment of participants with platinum-refractory or platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinomas.
详细描述
The drug being tested in this study is called alisertib (MLN8237). Alisertib is being tested to treat people who have platinum-refractory or platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. This study looked at the antitumor activity by response rate who would take alisertib.
The study enrolled 31 patients. Participants were categorized as per the disease state into 2 categories, refractory and resistant. Participants received:
• Alisertib 50 mg
All participants took alisertib 50 mg capsules every 12 hours each day for 7 days followed by a 14-day rest period in a 21-day cycle (up to 26 cycles).
This multi-center trial was conducted in France, Poland and the United States. The overall time to participate in this study was 12 months, unless it is determined that a participant would benefit from continued therapy beyond 12 months. Participants made multiple visits to the clinic, and were contacted up to a maximum of every 12 weeks up to 12 months after last dose of study drug for follow-up assessments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female participants 18 years or older.
- •Histologically or cytologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Postmenopausal at least 1 year, OR
- •Surgically sterile, OR
- •If childbearing potential, agree to 2 effective methods of nonhormonal contraception, or agree to completely abstain from heterosexual intercourse.
- •Able to provide written informed consent.
- •Within 7 days before study:
- •Absolute neutrophils (ANC) ≥ 1,500/μL
- •Platelets ≥100,000/ μL
- •Total bilirubin must be < 1.5 times upper limit of the normal (ULN)
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be ≤ 2.5 times the ULN. AST and ALT may be elevated up to 5 times the ULN if ascribed to metastatic liver disease.
- •Creatinine clearance ≥ 30 mL/minute
- •Platinum-refractory or -resistant disease.
- •Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) OR Cancer antigen (CA) 125 level of > 40 units/mL AND clinical evidence disease.
- •Recovered from effects of prior therapy.
排除标准
- •Pregnant or lactating.
- •Serious illness that could interfere with protocol completion.
- •Investigational treatment 28 days prior to first dose.
- •Maximum 4 prior systemic therapies: 2 platinum-based, 1 nonplatinum cytotoxic, 1 biological.
- •Known Central Nervous System metastases.
- •Prior allogeneic bone marrow or organ transplantation.
- •Radiotherapy within 21 days prior to first dose.
- •Radiotherapy to > 25% bone marrow.
- •Major surgery or infection requiring systemic antibiotic therapy within 14 days prior to first dose.
- •Inability to swallow orally administered medication.
- •Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected.
- •Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C.
研究组 & 干预措施
Alisertib 50 mg
Alisertib 50 mg, capsules, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 26 Cycles).
干预措施: Alisertib (Drug)
结局指标
主要结局
Combined Best Overall Response Rate Based on Investigator Assessment
时间窗: Every 2 cycles up to 12 months until progressive disease (PD); Participants who discontinue study drug before PD: Follow-Up (FU)-every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months)
Combined objective response rate is defined as the percentage of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 or response by Cancer antigen (CA) 125 criteria. According to RECIST: CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter of target lesions. CA 125 response criteria is defined as either: A 50% decrease from 2 initially elevated samples; the sample demonstrating the 50% decrease must have been confirmed by a fourth sample 28 days later (a total of 4 samples required) or A serial decrease of \> 75% over 3 samples; the third sample was to be obtained 28 days after the second (a total of 3 samples required).
次要结局
- Time To Progression (TTP)(Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months))
- Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events(First dose to 30 days past last dose (Up to 18.9 Months))
- Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events(Baseline, Cycle 1 Days 8 and 15, then Day 1 of every cycle (21 days), End of Treatment, End of Study/FU every 12 weeks for up to 12 months (Up to 22 Months))
- Progression Free Survival (PFS)(Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months))
- Clinical Benefit Rate(Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months))
- Duration Of Response (DOR)(Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months))
- Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events(Baseline, Cycle 1 Days 8 and 15, then Every cycle Days 1, 8 and 15 to End of Treatment Up to 18.0 Months)