2024-519369-24-00招募中3 期
C2321008: A PHASE 3, RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED STUDY OF MEVROMETOSTAT (PF-06821497) WITH ENZALUTAMIDE IN METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER (MEVPRO-3)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Pfizer Inc.
- 入组人数
- 50
- 试验地点
- 11
- 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 mevrometostat in combination with enzalutamide is superior to placebo in combination with enzalutamide in prolonging blinded independent central review (BICR)-assessed radiologic progression-free survival (rPFS)
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 of age or older (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 prostate cancer documented by positive bone scan (for bone disease) or metastatic lesion(s) on CT or MRI scan (for soft tissue/visceral disease).
- •Resolution of acute effects of any prior therapy to either baseline severity or CTCAE Grade ≤1 (except for AEs which do not constitute a safety risk in the investigator’s judgement).
- •Participants cannot have received any cytotoxic chemotherapy, ARPIs (eg, enzalutamide, apalutamide, abiraterone acetate, or darolutamide), any other systemic anticancer therapies for mCSPC, with the following exceptions: a.ADT (chemical or surgical) must be started prior to randomization and must continue throughout the study. Prior therapy with up to 3 months of ADT (with or without antiandrogens) is allowed with no radiographic evidence of disease progression or rising PSA levels indicative of disease progression prior to Day 1.; b. Treatment with estrogens, cyproterone acetate or first-generation antiandrogens is allowed until randomization, but must be discontinued prior to randomization.; c. Participants may have received 1 course of palliative radiation or surgery for symptomatic control secondary to prostate cancer, which should be completed at least 2 weeks prior to randomization.
- •Participants must have ECOG PS 0 or 1.
排除标准
- •Any medical or psychiatric condition including any active suicidal ideation in the past year or suicidal behavior in the past 5 years or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
- •Inability to swallow oral medications.
- •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, or other clinically significant cardiovascular disease as assessed by the investigator. If a participant has a cardiac rhythm device/pacemaker placed and QTcF >470 ms, the participant may be considered eligible. QTcF >480 ms 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 nonmelanoma 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.
- •In the opinion of the investigator, any clinically significant gastrointestinal disorder affecting absorption.
- •Known allergic or hypersensitivity reactions to mevrometostat or its excipients or to enzalutamide or its excipients.
- •Current use of any prohibited concomitant medication(s) or unwillingness or inability to use a required concomitant medication(s).
- •Prior treatment with: a.ADT in the adjuvant/neoadjuvant setting, where the completion of ADT was <12 months prior to randomization and the total duration of ADT was >36 months; b. ARPI’s such as abiraterone, apalutamide, darolutamide, enzalutamide or other investigational ARPI’s; c.Cytochrome P17 enzyme inhibitors such as oral ketoconazole as anticancer treatments for prostate cancer; d. Chemotherapy including docetaxel or immunotherapy for prostate cancer.; e. Radiopharmaceuticals (ie, 177Lu-PSMA-617, radium-223); f. CDK4/6 inhibitors; g. Any other anticancer treatment for metastatic prostate cancer, excluding palliative radiotherapy/surgery and ADT as discussed above.
- •Previous administration of an investigational product (drug or vaccine) which does not meet exclusion criterion 7 within 30 days or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). Participation in studies of other investigational products (drug or vaccine) at any time during participation in this 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 Appendix 7 Section 10.7.2 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.
- •Major surgery (as defined by investigator) from which the participant has not fully recovered at least 28 days prior to randomization.
- •Hepatic dysfunction defined as having any 1 of the following, which may be confirmed by a single repeat test, if necessary: a. Total bilirubin ≥1.5 x ULN (≥3 x ULN for participants with documented Gilbert’s syndrome, direct bilirubin >ULN is exclusionary) b. AST >2.5 x ULN c. ALT >2.5 x ULN
- •Hematologic abnormalities defined as having any 1 of the following, which may be confirmed by a single repeat test, if necessary: a. ANC <1500/mm3; b. Platelets <100,000/mm3, independent of transfusion within 14 days of randomization; 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.
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)
- Proportion of participants with measurable soft tissue disease at baseline with an objective response per RECIST 1.1 (assessed by BICR and investigator)
- Duration of soft tissue response per RECIST 1.1 (assessed by BICR and investigator)
- Proportion of participants with prostate-specific antigen (PSA) response ≥50% in participants with detectable PSA values at baseline
- Time to PSA progression
- Time to initiation of antineoplastic therapy
- Time to first symptomatic skeletal event
- Time from randomization to castration-resistant prostate cancer (CRPC)
- Type, incidence, severity (as graded by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] v5.0), seriousness and relationship to study medications of adverse events (AEs) and any laboratory test and electrocardiogram (ECG) abnormalities
- PK characterized by pre-dose trough and post-dose plasma concentrations of mevrometostat at selected visits
- Change from baseline and time to confirmed deterioration in participantreported worst pain symptoms per Brief Pain Inventory – Short Form (BPI-SF)
- Change from baseline in health-related quality of life (HRQoL), functioning, and symptoms and time to definitive deterioration per Functional Assessment of Cancer Therapy – Prostate (FACT-P)
- Change from baseline and time to definitive deterioration in participantreported prostate cancer specific functioning and symptoms per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Prostate Cancer 25 (EORTC QLQ-PR25)
- Change from baseline and time to confirmed deterioration in participantreported fatigue symptoms per Brief Fatigue Inventory (BFI)
- Change from baseline in participant-reported general health status per European Quality of Life 5-Dimensions 5-Level (EQ-5D-5L)
- ctDNA burden at baseline and on study
研究者
Clinical Medical Lead
Scientific
Pfizer Inc.
研究点 (11)
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