2024-511652-40-00招募中3 期
C2321003: 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 Inc.
- 入组人数
- 328
- 试验地点
- 81
- 主要终点
- BICR assessed rPFS per RECIST 1.1 (soft tissue disease) and PCWG3 (bone disease).
研究概览
简要总结
To demonstrate that PF-06821497 in combination with enzalutamide is superior to placebo in combination with enzalutamide in prolonging rPFS.
研究设计
- 分配方式
- Randomized
- 主要目的
- Overall Design
- 盲法
- Double (Subject, Carer, Investigator)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male participants aged ≥18 years (or the minimum age of consent in accordance with local regulations) at screening.
- •Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features (neuroendocrine differentiation and other histologic components are permitted if adenocarcinoma is the primary histology). For participants without a prior histological diagnosis, a baseline de novo biopsy must be used to confirm the diagnosis.
- •Metastatic disease in bone documented on bone scan, or in soft tissue documented on CT/MRI scan.
- •Surgically or medically castrated, with serum testosterone ≤50 ng/dL (≤1.73 nmol/L) at screening.
- •Progressive disease in the setting of medical or surgical castration as defined by meeting 1 or more of the following 3 criteria: a. Prostate specific antigen (PSA) progression defined by rising PSA of at least 2 consecutive rises in most recent PSA to be documented over a reference value (measure 1) taken at least 7 days apart within the last 12 months. If the third PSA measure is not greater than the second measure, a fourth PSA measure is required to be taken and be greater than the second measure. The last of these PSA values, obtained before randomization must be ≥1 μg/L if qualifying only by PSA progression; b. Soft tissue disease progression as defined by RECIST 1.1.; c. Bone disease progression defined by PCWG3 with 2 or more new metastatic bone lesions on a whole-body radionuclide bone scan.
- •Prior to randomization, there must be resolution of acute effects of any prior therapy to either baseline severity or CTCAE Grade ≤1 (except for AEs such as alopecia and peripheral neuropathy not constituting a safety risk in the investigator’s judgment).
- •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/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
- •Inadequate renal function defined by an eGFR <45 mL/min/1.73 m².. Based upon participant age at screening, eGFR is calculated using the recommended formulas in Section 10.7.1 to determine eligibility and to provide a baseline to quantify any subsequent kidney safety events.
- •Hepatic dysfunction defined as: a. Total bilirubin ≥1.5 × ULN; b. AST >2.5 × ULN; c. ALT >2.5 × ULN
- •Hematologic abnormalities defined as: a. ANC <1500/mm3; b. Platelets <100,000/μL; c. Hemoglobin <9 g/dL, independent of transfusion within 14 days of randomization
- •Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
- •Clinically significant cardiovascular disease, defined as: a. Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Class III or IV), cerebrovascular accident, or symptomatic pulmonary embolism or other clinically significant episode of thromboembolic disease, congenital long QT syndrome, Torsade de Pointes, clinically important arrhythmias, left anterior hemiblock (bifascicular block), ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2; b. Cardiac rhythm device/pacemaker.; c. QTcF >480 msec on screening ECG.
- •CNS pathology/neurological findings: a. Known or suspected brain metastasis or active leptomeningeal disease.; b. Symptomatic or impending spinal cord compression or cauda equina syndrome.; c. Participants with epidural disease, canal disease and prior cord involvement are NOT excluded if those areas have been treated, are stable, and not neurologically impaired.; d. Clinically significant history of seizure or any condition that may predispose to seizure (eg, prior cortical stroke, significant brain trauma). Also, history of unexplained loss of consciousness or transient ischemic attack within 12 months of randomization.
- •Any history of myelodysplastic syndrome, acute myeloid leukemia, or any other prior malignancy except for any of the following: a. Carcinoma in situ or non-melanoma skin cancer.; b. Any prior malignancies ≥3 years before randomization with no subsequent evidence of recurrence or progression regardless of the stage.; c. Stage 0 or Stage 1 cancer <3 years before randomization that has a remote probability of recurrence or progression in the opinion of the investigator.
- •Participants must be treatment naïve at the mCRPC stage, eg, participants cannot have received any cytotoxic chemotherapy (includes but not limited to docetaxel), received ARSI/ abiraterone acetate in mCRPC, mCSPC or non-metastatic PC. Prior docetaxel in mCSPC is allowed.
- •Prior treatment with opioids for pain related to either primary prostate cancer or metastasis within 28 days prior to randomization are not permitted.
- •Previous administration with an investigational product (drug or vaccine which does not meet exclusion criterion 5 above) within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
- •Current use or anticipated need for drugs that are known strong CYP3A4/5 inhibitors and inducers (with exception of enzalutamide as part of this study) outlined in Section 6.9.1 and Section 6.9.2, including their administration within 10 days or 5 half-lives, whichever is longer prior to randomization.
- •Major surgery or palliative localized radiation therapy within 14 days before randomization.
结局指标
主要结局
BICR assessed rPFS per RECIST 1.1 (soft tissue disease) and PCWG3 (bone disease).
BICR assessed rPFS per RECIST 1.1 (soft tissue disease) and PCWG3 (bone disease).
次要结局
- OS (alpha protected)
- TTPP (alpha protected): assessed using time to first ≥2- point increase from baseline score on BPISF Item 3 (Worst Pain) observed at 2 consecutive visits or the initiation of short- or long-acting opioid use for pain
- Proportion of participants with measurable soft tissue disease at baseline with an objective response per RECIST 1.1 (assessed by BICR)
- Duration of soft tissue response per RECIST 1.1 (assessed by BICR)
- Proportion of participants with PSA response ≥50% in participants with detectable PSA values at baseline
- Time to PSA progression
- Time to initiation of new antineoplastic therapy
- Time to initiation of cytotoxic chemotherapy
- Time to first symptomatic skeletal event
- PFS2 based on investigator assessment separately
- Type, incidence, severity (as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0), seriousness and relationship to study medications of AEs and any laboratory test and ECG abnormalities
- ctDNA burden at baseline and on study
- PK characterized by pre-dose trough and post-dose plasma concentrations of PF- 06821497 at selected visits
- Change from baseline in participant reported pain symptoms per BPI-SF; Change from baseline in BPI-SF Item 3 (Worst Pain) at Cycle 7 Day 1 (Week 25); Change from baseline in HRQoL, functioning and symptoms per FACT-P; Change from baseline in participant reported health status per EQ- 5D-5L; Symptomatic toxicity and the overall side effect burden as measured by items from the PRO-CTCAE and FACT-GP5; Time to definitive deterioration in participant reported HRQoL and physical well-being per FACT-P
研究者
Clinical Medical Lead
Scientific
Pfizer Inc.
研究点 (81)
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