CTRI/2025/05/086865尚未招募1 期
A Phase I/Ib, Multi-center, Randomized, Open-Label Study to Assess the Safety, Tolerability and Anti-tumor Activity of RP12146, a Poly (ADP-ribose) Polymerase (PARP) Inhibitor, in Patients with BRCA1/2 Mutated Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 40
- 试验地点
- 6
- 主要终点
- Incidence of Adverse Events (AE), Grade 3/4 AEs, Serious Adverse Events (SAEs), and Dose-limiting toxicities (DLTs),
研究概览
简要总结
| This is a phase I/Ib, open label, multi-center study in metastatic castration-resistant prostate cancers who have failed at least one line of androgen receptor (AR) directed therapies (e.g., abiraterone acetate, enzalutamide, and apalutamide) or one prior taxane-based chemotherapy (e.g., docetaxel) and have somatic/germline BRCA1/2 mutation. |
In Phase-I (Dose Escalation) study, optimal dose either 200mg BID or 400mg BID as decided by Data and Safety Monitoring Board (DSMB) based on emerging safety and tolerability data. This will be followed by Phase-I/b (Dose Expansion) study where two parallel expansion groups will receive IP, one with optimal dose and second with one dose lower than optimal dose.
In Phase-I, approximately 6-9 patients will be enrolled while in Phase-Ib remaining patients to complete enrollment of 40 patients.
Each cycle is of 28 days. Patients will receive IP until disease progression or consent withdrawal, or unacceptable toxicity leading to discontinuation of the patients. Hence duration of participation in this study is variable, and patients will continue in the study until disease progression, unequivocal clinical progression, consent withdrawal, or unacceptable toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 90.00 Year(s)（—）
- 性别
- Male
入选标准
- •For Part A Patients must be greater than equal to 18 years of age or older at the time of signing informed consent Patients must have histologically and or cytologically confirmed metastatic castration-resistant prostate cancer (mCRPC) Patients must provide informed consent for screening of BRCA1 or BRCA2 mutation status For Part B Provision of full informed consent prior to any study-specific procedures.
- •Patients must be greater than equal to 18 years of age, at the time of signing informed consent.
- •Patients who have histologically and/or cytologically confirmed mCRPC.
- •Presence of a deleterious somatic or germline BRCA1 and BRCA2 mutation as confirmed by the central genomics testing laboratory.
- •Disease status is defined as: Surgically or medically castrated male patients with metastatic prostate cancer whose disease has progressed following at least one line of androgen receptor (AR) directed therapies or one prior taxane-based chemotherapy (e.g., docetaxel).
- •Patients with at least one measurable lesion per RECIST 1.1 at baseline that can be accurately assessed by CT or MRI scan and is suitable for repeated assessment at follow-up visits.
- •ECOG performance status 0 to
- •Life expectancy of at least 3 months.
- •Adequate bone marrow, liver, and renal functions as assessed within 7 (± 2) days before the first dose of the study drug.
- •Patient with vasectomy or patient who agrees to remain completely abstinent or who uses barrier contraceptive measures and agrees to refrain from donating sperm during the entire study treatment period.
- •Ability to swallow and retain oral medication.
- •Willingness and capability to comply with the requirements of the study.
排除标准
- •Patients with castration-sensitive or non-metastatic castration-resistant prostate cancer Patients who have had or are receiving anticancer therapy such as chemotherapy, biologic therapy, or any investigational product within 4 weeks or 5 half-lives prior to C1D1, whichever is shorter Patients who have not recovered from acute toxicities defined as NCI-CTCAE grade greater than 1 of previous therapy except treatment-related alopecia Prior treatment with a PARP inhibitor such as Olaparib, Rucaparib, Talazoparib, or any other investigational PARP inhibitor Major surgery within 4 weeks of starting study treatment or any patient who has not recovered from the effects of major surgery Patients with symptomatic uncontrolled brain metastasis HIV-positive patients who are on antiretroviral therapy, or patients with active hepatitis C virus infection or active hepatitis B virus infection Active gastrointestinal tract disease with malabsorption syndrome or uncontrolled inflammatory gastrointestinal diseases such as Crohn’s disease or ulcerative colitis Myocardial infarction within 6 months before starting therapy, symptomatic congestive heart failure New York Heart Association greater than Class II, unstable angina, or unstable cardiac arrhythmia requiring medication, or clinically relevant findings in the ECG such as second or third-degree AV block, significant prolongation of the QTcF interval unless agreed otherwise between the investigator and the medical monitor Concurrent disease or condition that would interfere with study participation or safety Concurrent medications or substances with the potential to affect the activity or pharmacokinetics of RP12146 Symptomatic spinal cord compression unless it is appropriately treated and clinically stable, or impending spinal cord compression unless it is asymptomatic Patients with other active malignancies at the time of screening with the exception of basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin A serious uncontrolled medical disorder or active infection which would impair the ability of the patient to receive protocol therapy or whose control may be jeopardized by the complications of this therapy.
结局指标
主要结局
Incidence of Adverse Events (AE), Grade 3/4 AEs, Serious Adverse Events (SAEs), and Dose-limiting toxicities (DLTs),
时间窗: 28 days for DLT.
To determine the Maximum tolerated dose (MTD)/Optimal dose of RP12146
时间窗: 28 days for DLT.
Incidence of drug interruption, dose modification, and drug discontinuation
时间窗: 28 days for DLT.
次要结局
- Overall Response Rate (ORR), Duration of Response (DoR), Clinical Benefit Rate (CBR), and Radiographic Progression-Free Survival (rPFS) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1(Prostate Specific Antigen (PSA) response defined as greater than 50 percent decline from baseline to lowest post-baseline PSA)
研究者
研究点 (6)
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