NCT01682772Unknown2 期
A Phase II Trial of Olaparib in Patients With Advanced Castration Resistant Prostate Cancer (TOPARP)
Institute of Cancer Research, United Kingdom2 个研究点 分布在 1 个国家目标入组 148 人开始时间: 2012年7月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 148
- 试验地点
- 2
- 主要终点
- Response rate to Olaparib
研究概览
简要总结
This is an open-label, single arm, two part adaptive design phase II trial of Olaparib in patients with advanced castration resistant prostate cancer.
The trial aims to evaluate the the anti-tumour activity of Olaparib in metastatic castration resistant prostate cancer, identify molecular signatures of tumour cells in responding and non-responding patients, and to identify predictive biomarkers of Olaparib response.
详细描述
Patients with advanced castration resistant prostate cancer will receive single agent Olaparib at a dose of 400mg twice daily, continuously on a 28 day cycle. Olaparib will be administered until objective disease progression or unacceptable toxicity or patient withdrawal for whatever reason
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- Male
- 接受健康志愿者
- 否
入选标准
- •Subject capable of understanding & complying with protocol requirements & signed the informed consent form
- •Minimum age 18 years
- •Histologically confirmed adenocarcinoma of the prostate with tumour tissue available for molecular analyses
- •At least one but no more than two previous taxane-based chemotherapy regimens. If docetaxel chemotherapy is used more than once, this will be considered as one regime. Patients may have had prior exposure to cabazitaxel treatment
- •At least 28 days since the completion of prior therapy, including major surgery, chemotherapy & other investigational agents. Clinically relevant sequelae should have resolved to grade 1 or less prior to recommencing treatment. For hormonal treatment & radiotherapy refer to the protocol guidelines
- •Documented prostate cancer progression as described in the protocol.
- •Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nM). If the patient is being treated with LHRH agonists this must have been initiated at least 4 weeks prior to Cycle 1 Day 1 & must be continued throughout the study.
- •Eastern Cooperative Oncology Group Performance Status of 0, 1, 2
- •Life expectancy > 12 weeks
- •Able to swallow a whole tablet
- •Patient & the patient's partner of childbearing potential, must agree to use medically accepted methods of contraception during the course of the study & for 3 months after the last dose of study drug
- •Agreeable to have all the biomarker studies including the paired fresh tumour biopsies.
- •CTC count of 5 cells/7.5mls blood or more at screening. Note: For Part B, CTC count >5 cells/7.5mls blood is not mandatory if patient has measurable disease by modified RECIST and a lesion >2cm and PSA greater than or equal to 2ng/ml at screening.
- •Adequate bone marrow, hepatic & renal function as defined in the protocol
- •For Part B only, patients must have genomic defects associated with olaparib sensitivity identified by NGS by the central lab.
排除标准
- •Surgery, or local prostatic intervention (excluding a prostatic biopsy) less than 28 days of Cycle 1 Day 1
- •Less than 28 days from any active anticancer therapy or investigational agents. For hormonal treatment & radiotherapy refer to the guidelines outlined in the inclusion criteria
- •Prior treatment with a PARP inhibitor, platinum, cyclophosphamide or mitoxantrone chemotherapy
- •Uncontrolled intercurrent illness including, but not limited to, active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease), unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or psychiatric illness/social situations that would limit compliance with study requirements
- •Any acute toxicities due to prior chemotherapy & / or radiotherapy that have not resolved to a NCI-CTCAE v4.02 grade 0 or 1 with the exception of chemotherapy induced alopecia & grade 2 peripheral neuropathy
- •Malignancy within the previous 2-years with a > 30% probability of recurrence within 12 months with the exception of non-melanoma skin cancer, in-situ or superficial bladder cancer
- •Patients with myelodysplastic syndrome/acute myeloid leukaemia
- •Patients with known symptomatic brain metastasis are not suitable for enrollment. Patients with asymptomatic, stable, treated brain metastases are eligible for study entry
- •Patients with symptomatic or impending cord compression unless appropriately treated beforehand & clinically stable & asymptomatic
- •Patients who have experienced a seizure or seizures within 6 months of study treatment or who are currently being treated with cytochrome P450 enzyme inducing anti-epileptic drugs for seizures
- •Patients receiving any of the following classes of inhibitors of CYP3A4 (see protocol for guidelines & wash out periods)
- •Patients with gastrointestinal disorders likely to interfere with absorption of the study medication
- •Initiating bisphosphonate therapy or adjusting bisphosphonate dose/regimen within 30 days prior to Cycle 1 Day
- •Patients on a stable bisphosphonate regimen are eligible & may continue
- •Presence of a condition or situation, which, may put the patient at significant risk, confound the study results, or interfere significantly with participation in the study
研究组 & 干预措施
Olaparib 400mg
Experimental
Oral Olaparib at a dose of 400mg twice daily, continuously on a 28 day cycle
干预措施: Olaparib (Drug)
Olaparib 300mg
Experimental
Oral Olaparib at a dose of 300mg twice daily, continuously on a 28 day cycle
干预措施: Olaparib (Drug)
结局指标
主要结局
Response rate to Olaparib
时间窗: Response will be evaluated 6 months post trial entry
Response will be defined on the basis of the following outcomes, if any of these occur patients will be considered to have responded: * Objective response by modified RECIST * PSA decline of ≥50% according to the Prostate Cancer Working Group 2 * Conversion of circulating tumour cell count from ≥5 cells/7.5ml blood at baseline to \<5 cells/7.5ml blood confirmed by at least two readings 4 weeks apart
次要结局
- Radiographic progression free survival(Radiographic progression free survival will be evaluated 6 months post trial entry)
- Time to PSA Progression(Time to PSA progression will be evaluated 6 months post trial entry)
- Time to radiographic progression(Will be evaluated 6 months post trial entry)
- Progression free survival(Progression free survival will be evaluated 6 months post trial entry)
- CTC count conversion rate(CTC count conversion rate will be evaluated 6 months post trial entry)
- Duration of PSA response(Duration of PSA response will be evaluated 6 months post trial entry)
- Number of participants with grade 3 or 4 adverse events as a measure of safety and tolerability.(Will be evaluated 1) when the first 5 and 10 participants have completed the 1st cycle of treatment and, 2) at 6 months post trial entry.)
- Overall survival(Will be evaluated 6 months post trial entry)
- PSA objective response(Will be evaluated 6 months post trial entry)
研究者
研究点 (2)
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