A PHASE 3, RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED STUDY OF PF-06821497 (MEVROMETOSTAT) WITH ENZALUTAMIDE IN METASTATIC CASTRATION RESISTANT PROSTATE CANCER (MEVPRO-2)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Pfizer
- 入组人数
- 900
- 试验地点
- 409
- 主要终点
- Radiographic Progression Free Survival (rPFS)
研究概览
简要总结
This study will explore whether a combination of the investigational drug PF-06821497 and enzalutamide will work better than taking enzalutamide alone in participants with mCRPC who are ARSi or abiraterone naïve.
详细描述
This is a global, multicenter, randomized Phase 3 study evaluating PF-06821497 (mevrometostat) in combination with enzalutamide versus placebo in combination with enzalutamide in participants with mCRPC where no systemic anti-cancer treatments have been initiated after documentation of mCRPC with the exception of ADT (androgen deprivation therapy) and first-generation anti-androgen agents. Prior treatment with any of the ARSi's enzalutamide, darolutamide, apalutamide, or abiraterone acetate, is not permitted in any setting. Chemotherapy is permitted in the castrate sensitive setting.
This study consists of a Screening Phase, Randomization, Treatment Phase, Safety Follow-up, and Long-Term Follow-up. Participants will be randomized on a 1:1 basis to receive (Arm A) PF-06821497 in combination with enzalutamide, or (Arm B) placebo in combination with enzalutamide.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double-blind study. Participants will receive PF-06821497 or matching placebo in a blinded fashion, as indicated in Section 6.1. Participants, investigators and site staff, and sponsor staff will be aware that participants in both study arms are receiving enzalutamide. Enzalutamide will be provided in an open-label manner to participants in each treatment arm.
Participants and their caregivers will be blinded to their assigned study intervention.
Investigators and other site staff will be blinded to participants' assigned study intervention Sponsor staff will be blinded to participants' assigned study intervention, except for sponsor staff involved in the assignment or distribution of study intervention.
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
- •Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features.
- •Metastatic disease in bone documented on bone scan, or in soft tissue documented on CT/MRI scan.
- •Progressive disease in the setting of medical or surgical castration.
- •ECOG performance status 0 or 1, with a life expectancy of ≥12 months as assessed by the investigator.
排除标准
- •Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation in the past year or suicidal behavior in the past 5 years or laboratory abnormality that make the participant inappropriate for the study.
- •Known history of active inflammatory gastrointestinal disease, chronic diarrhea, or previous gastric resection or lap-band surgery.
- •Clinically significant cardiovascular disease.
- •Known or suspected brain metastasis or active leptomeningeal disease or clinically significant history of seizure.
- •Any history of myelodysplastic syndrome, acute myeloid leukemia, or any other prior malignancy with a few exceptions.
- •Participants must be treatment naïve at the mCRPC stage, eg, no cytotoxic chemotherapy, radio-ligand therapy (i.e. 177Lu- PSMA-617), CDK4/6 inhibitors, 5-alpha reductase inhibitors for prostate cancer in any setting, androgen receptor signaling inhibitors (ARSi) including enzalutamide, apalutamide, darolutamide, poly ADP-ribose polymerase (PARP) monotherapy or other systemic anti-cancer treatment with the following exceptions:
- •Treatment with first-generation antiandrogen (ADT) agents, estrogens, progestins, cyproterone acetate;
- •Docetaxel treatment is allowed for mCSPC, as long as no signs of failure, or disease progression occurred during treatment or within 3 months of treatment completion.
- •Previous administration with an investigational product (drug or vaccine) within 30 days or 5 half-lives preceding the first dose of study intervention (whichever is longer).
- •Inadequate organ function.
研究组 & 干预措施
Arm B
Participants will receive Placebo BID (twice daily) + enzalutamide 160 mg QD (once daily)
干预措施: Placebo (Drug)
Arm A
Participants will receive PF-06821497 (875 mg) BID (twice daily) + enzalutamide 160 mg QD (once daily)
干预措施: PF-06821497 (Drug)
Arm B
Participants will receive Placebo BID (twice daily) + enzalutamide 160 mg QD (once daily)
干预措施: Enzalutamide (Drug)
Arm A
Participants will receive PF-06821497 (875 mg) BID (twice daily) + enzalutamide 160 mg QD (once daily)
干预措施: Enzalutamide (Drug)
结局指标
主要结局
Radiographic Progression Free Survival (rPFS)
时间窗: Randomization up to approximately 3 years
rPFS is defined as the time from the date of randomization to first objective evidence of radiographic progression as assessed in soft tissue per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or in bone per Prostate Cancer Clinical Trials Working Group 3 (PCWG3) guidelines by BICR, or death, whichever occurs first.
次要结局
- Overall survival (OS)(Randomization up to approximately 5 years)
- To demonstrate that PF-06821497 in combination with enzalutamide is superior to placebo in combination with enzalutamide in prolonging TTPP(Randomization up to approximately 3 years)
- Time to prostate specific antigen (PSA) progression.(Randomization up to approximately 3 years)
- Prostate Specific Antigen Response(Randomization up to approximately 3 years.)
- Time to initiation of antineoplastic therapy.(Randomization up to approximately 3 years.)
- Time to initiation of cytotoxic chemotherapy.(Randomization up to approximately 3 years)
- Time to first symptomatic skeletal event(Randomization up to approximately 3 years.)
- Progression free survival on next line of therapy(Randomization up to approximately 3 years)
- Incidence of Adverse Events(Randomization up to approximately 5 years)
- To assess circulating tumor DNA (ctDNA) at baseline and on treatment to evaluate tumor burden.(Baseline up to approximately 3 years.)
- To evaluate the PK of PF-06821497 when dosed with enzalutamide(Cycle 1 Day 15 to last PK draw at Cycle 6 Day 1 (cycle length is 28 days))
- Change from baseline in patient reported pain symptoms per Brief Pain Inventory-Short Form (BPI-SF)(Randomization up to approximately 5 years)
- Change from baseline in BPI-SF Item 3 (Worst Pain) at Cycle 7 Day 1 (Week 25)(Randomization up to Week 25)
- Change from baseline in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy - Prostate (FACT-P)(Randomization up to approximately 5 years)
- Change from baseline in patient reported health status per European Quality of Life 5-Dimension 5 Level (EQ-5D-5L)(Randomization up to approximately 5 years)
- Symptomatic toxicity as measured by items from the Patient-Reported Outcome CTCAE (PRO-CTCAE)(Randomization up to approximately 5 years)
- Time to definitive deterioration in patient-reported health related quality of life (HRQoL) per FACT-P(Randomization up to approximately 5 years)
- Duration of Response (DoR) in measurable soft tissue disease(Randomization up to approximately 3 years.)
- To demonstrate that PF-06821497 in combination with enzalutamide is superior to placebo in combination with enzalutamide in prolonging Time To Pain Progression (TTPP)(Randomization up to approximately 5 years)
- Objective Response Rate (ORR)(Randomization up to approximately 3 years)
- Time to initiation of antineoplastic therapy.(Randomization up to approximately 5 years.)
- Time to initiation of cytotoxic chemotherapy.(Randomization up to approximately 5 years)
- Progression free survival on next line of therapy(Randomization up to approximately 5 years)
- Overall side effect burden as measured by the FACT- GP5(Randomization to approximately 5 years)