2024-511650-50-00招募中3 期
C2321014: A PHASE 3, RANDOMIZED, OPEN-LABEL STUDY OF PF-06821497 (MEVROMETOSTAT) IN COMBINATION WITH ENZALUTAMIDE COMPARED WITH ENZALUTAMIDE OR DOCETAXEL IN PARTICIPANTS WITH METASTATIC CASTRATION RESISTANT PROSTATE CANCER PREVIOUSLY TREATED WITH ABIRATERONE ACETATE (MEVPRO-1)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Pfizer Inc.
- 入组人数
- 205
- 试验地点
- 59
- 主要终点
- BICR assessed rPFS per RECIST v1.1 (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 PCT of enzalutamide or docetaxel in prolonging rPFS.
研究设计
- 分配方式
- Randomized
- 主要目的
- Overall Design
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 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 surgical or medical castration as defined by 1 or more of the following 3 criteria:PSA progression defined as a minimum of two rising PSA levels with an interval of ≥1 week between each determination within the last 12 months. The PSA value at the Screening visit must be ≥1 ng/mL if confirmed rise in PSA is the only indication of progression per PCWG3 criteria;Soft tissue disease progression as defined by RECIST v1.1;Bone disease progression defined by PCWG3 with 2 or more new metastatic bone lesions on a whole-body radionuclide bone scan.
- •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 - 2, with life expectancy of at least 6 months as assessed by the investigator.
排除标准
- •Any medical (including active or clinically significant bacterial, fungal or viral infection) 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 m
- •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. For eligibility assessment based upon estimated renal function, the higher of the screening and baseline eGFR values may be used.
- •Hepatic dysfunction defined as: Total bilirubin ≥1.5 × ULN; AST ≥2.5 × ULN; ALT ≥2.5 × ULN
- •Previous administration with an investigational product (drug or vaccine which does not meet exclusion criterion 5 above) within 30 days or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
- •Hematologic abnormalities defined as: ANC ≤1500/mm3; Platelets ≤100,000/μL; 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: 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; Cardiac rhythm device/pacemaker; QTcF >480 msec on screening ECG.
- •CNS pathology/neurological findings: Known or suspected brain metastasis or active leptomeningeal disease; Symptomatic or impending spinal cord compression or cauda equina syndrome; 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; 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: Carcinoma in situ or non-melanoma skin cancer; Any prior malignancies ≥3 years before randomization with no subsequent evidence of recurrence or progression regardless of the stage; 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.
- •Prior treatment for prostate cancer at any stage with any cytotoxic chemotherapy, radioligand therapy (ie, 177Lu-PSMA-617, radium-223), ARSi (including enzalutamide, apalutamide, darolutamide), PARP monotherapy or other systemic anti-cancer treatment (approved drugs or experimental compounds such as, antibody therapy, immunotherapy, gene therapy, angiogenesis inhibitors, CDK4/6 inhibitors, EZH2 inhibitors) with the following exceptions: a. a. Treatment with first-generation antiandrogen agents (eg, bicalutamide, nilutamide, and flutamide), but must be discontinued prior to the first dose of study medication.; b. b. 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.
- •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 Sections 6.9.1 and 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 v1.1 (soft tissue disease) and PCWG3 (bone disease).
BICR assessed rPFS per RECIST v1.1 (soft tissue disease) and PCWG3 (bone disease).
次要结局
- Time to first symptomatic skeletal event.
- OS (alpha protected).
- Proportion of participants with measurable soft tissue disease at baseline with an objective response per RECIST v1.1 (assessed by BICR).
- Proportion of participants with PSA response ≥50% in participants with detectable PSA values at baseline.
- Time to PSA progression.
- Duration of response in soft tissue disease per RECIST v1.1 (assessed by BICR).
- Time to initiation of new antineoplastic therapy.
- PFS2 based on investigator assessment
- Change from baseline in patient reported pain symptoms per BPI-SF
- Change from baseline in HRQoL, functioning and symptoms per FACT-P
- Symptomatic toxicity and the overall side effect burden as measured by items from the Patient-Reported Outcome CTCAE (PRO-CTCAE) and FACT-GP5
- Time to confirmatory deterioration in patient-reported pain symptoms per BPISF Item 3 “worst pain in 24 hours”
- ctDNA burden at baseline and on study.
- Type, incidence, severity (as graded by NCI CTCAE v5.0), seriousness and relationship to study medications of AEs.
- Change from baseline in patient reported health status per EQ-5D-5L
- Time to definitive deterioration in patientreported HRQoL and physical well-being per FACT-P.
- PK characterized by pre-dose trough and post-dose plasma concentrations of PF- 06821497 at selected visits.
研究者
Clinical Medical Lead
Scientific
Pfizer Inc.
研究点 (59)
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