A Randomized Phase II Trial to Evaluate the Antitumor Activity of Enzalutamide and Talazoparib (PF-06944076) for the Treatment of Metastatic Hormone-naïve Prostate Cancer
概览
- 阶段
- 2 期
- 干预措施
- Enzalutamide
- 疾病 / 适应症
- Metastatic Prostate Cancer
- 发起方
- MedSIR
- 入组人数
- 54
- 试验地点
- 8
- 主要终点
- Prostate specific antigen complete response (PSA-CR)
- 状态
- 已完成
- 最后更新
- 11个月前
概览
简要总结
This is a multicenter, open-label, randomized, two-arm, phase II clinical trial to evaluate the efficacy and safety of talazoparib (PF-06944076) in combination with enzalutamide in patients with metastatic hormone-naïve prostate cancer (mHNPC)
详细描述
Men age ≥ 18 years with high-volume mHNPC that are not candidates for curative intent and have not received previous systemic treatment with any other agent for unresectable locally advanced or mHNPC. After signing ICF and confirm eligibility, patients will start treatment with enzalutamide in addition to standard ADT. After 2 cycles of enzalutamide-containing regimen, patients will be randomized in a 1:2 ratio to: Cohort A - Enzalutamide 160 mg orally daily continuously; Cohort B - Enzalutamide 160 mg in combination with talazoparib (PF-06944076) 0.5 mg, both orally daily and continuously in 28-day cycles. In either arm, patients will be requested to continue ADT throughout trial participation (unless surgical castration). Randomization will be stratified based on HR gene alterations (presence versus absence/unknown) detected in the baseline biopsy. Patients will receive treatment until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason. Patients discontinuing the study treatment period will enter a post-treatment follow-up period during which survival and at least the first two new anti-cancer therapies will be collected every six months (± 14 days) from the last dose of investigational product until the end of study (EoS).
研究者
入排标准
入选标准
- •Adult patients (\>18 y.o.) who signed informed consent form (ICF) prior to participation in any study-related activities.
- •Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •High-volume metastatic disease documented on bone scan or computed tomography (CT)/magnetic resonance imaging (MRI) scan, defined as the presence of either visceral disease and/or at least four bone metastases on bone scan, with at least one of them beyond spine/pelvis.
- •Life expectancy of ≥ 12 months.
- •Histologically confirmed adenocarcinoma of the prostate without predominance of small-cell or neuroendocrine features according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines based on local testing on the most recent analyzed biopsy.
- •Note: Central confirmation of adenocarcinoma is not required for study entry. However, tissue blocks, or slides, must be submitted to confirm the diagnoses by a Sponsor-designated central laboratory retrospectively and/or exploratory biomarker analyses.
- •Willingness and ability to provide tumor paired biopsies during the study participation in order to perform exploratory studies. At the study entry, the most recent tumor biopsy since last progression from either metastatic or primary tissues will be provided. If not feasible, patient eligibility should be evaluated by a Sponsor's qualified designee.
- •Adequate hematologic and organ function within 28 days before the first study treatment on Cycle 1 Day 1, defined by the following:
- •Hematological: White blood cell (WBC) count \> 3.0 x 109/L; Absolute neutrophil count (ANC) \> 1.5 x 109/L; Platelet count \> 100.0 x109/L; Hemoglobin (Hb) \> 9.0 g/dL.
排除标准
- •Prior treatment with enzalutamide, apalutamide, darolutamide or abiraterone acetate.
- •History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills.
- •Known hypersensitivity to recombinant proteins, or any excipient contained in the drug formulation for talazoparib (PF-06944076) and enzalutamide.
- •Prior systemic therapy for metastatic prostate cancer (mPCa). Note: Initiation of androgen deprivation therapy (ADT) within 4 weeks prior to study entry would be allowed (with or without first-generation antiandrogens), providing a tumor biopsy sample was taken prior to initiation of ADT is made available for biomarker studies and upon approval by the sponsor. If patient was started on first-generation antiandrogens, these would be discontinued on prior to randomization.
- •Note: Patients relapsing after having received an ADT-based regimen in neoadjuvant or adjuvant setting will be suitable for the study if metastatic progression occured while on non-castrate testosterone levels or at least 12 months after discontinuation of ADT.
- •Treatment with approved or investigational cancer therapy within 28 days (or 5 half-lives of the drug- whichever is longer) prior to initiation of study treatment.
- •Known or suspected brain metastases or active leptomeningeal disease.
- •Symptomatic or impending spinal cord compression or cauda equina syndrome.
- •Subject has a history of seizure or any condition that may predispose to seizure (i.e. prior significant brain trauma, brain vascular malformations, ...), or subjects that have had unexplained loss of consciousness or transient ischemic attacks within 1 year prior to scheduled Day 1 of treatment.
- •Therapeutic radiation therapy within 14 days (seven days for limited-field palliative radiotherapy) prior to study enrolment, or patients who have not recovered from radiotherapy-related toxicities to grade ≤ 1 according to National Cancer Insitute ́s Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v.)5.
研究组 & 干预措施
Control Arm (Arm A)
Patients will receive enzalutamide capsules orally once daily continuously (160 mg) in addition to standard ADT (unless surgical castration).
干预措施: Enzalutamide
Interventional Arm (Arm B)
Patients will receive enzalutamide capsules 160 mg in combination with talazoparib (PF-06944076) capsules 0.5 mg, both orally daily and continuously in 28-day cycle, in addition to standard ADT (unless surgical castration).
干预措施: Enzalutamide
Interventional Arm (Arm B)
Patients will receive enzalutamide capsules 160 mg in combination with talazoparib (PF-06944076) capsules 0.5 mg, both orally daily and continuously in 28-day cycle, in addition to standard ADT (unless surgical castration).
干预措施: Talazoparib
结局指标
主要结局
Prostate specific antigen complete response (PSA-CR)
时间窗: Baseline up to 12 months
The primary efficacy endpoint for the study is the PSA-CR. The PSA-CR is defined as the percentage of patients with PSA \< 0.2 ng/mL divided by the number of patients in the analysis set.
次要结局
- Efficacy determined by Time to development of castration resistant (TTCR) prostate cancer(Baseline up to 12 months)
- Efficacy determined by Prostate specific antigen complete response (PSA-CR)(Baseline up to 7 months)
- Efficacy determined by PSA response(Baseline up to 7 and 12 months)
- Efficacy determined by Prostate-Specific Antigen progression-free survival (PSA-PFS)(Baseline up to 12 months)
- Efficacy determined by Radiological progression-free survival (rPFS)(Baseline up to 12 months)
- Efficacy determined by Overall survival (OS)(Baseline up to 12 months)
- Incidence of adverse events (AEs)(Up to 53 months after study start)
- Efficacy determined by Time to Clinical Progression (TCP)(Baseline up to 12 months)
- Efficacy determined by Prostate-Specific Antigen progression of disease (PSA-PD)(Baseline up to 12 months)