A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Mevrometostat (PF-06821497) With Enzalutamide in Metastatic Castration-Sensitive Prostate Cancer (MEVPRO-3)
Study Identifier:
C2321008
CT.gov Identifier:
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
Study Contact Information:
N/A
Recruiting
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Study Summary
This study will explore whether a combination of the investigational drug mevrometostat (PF-06821497) and enzalutamide will work better than taking enzalutamide alone in participants with mCSPC who are ARPI naïve and have not yet received chemotherapy in the mCSPC setting.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
III
Sex
Male
Age
18+ years
Study Drug
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Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
Inclusion criteria
- Inclusion Criteria
- * 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.
- * Metastatic prostate cancer documented by positive bone scan (for bone disease) or metastatic lesion(s) on CT or MRI (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 must have ECOG PS 0 or 1.
- CFDA
- 1 Male study participants aged 18 years and above (or the minimum age of informed consent as determined by local regulations) at the time of screening were enrolled.
- 2 Histologically or cytologically confirmed prostate adenocarcinoma without small cell features (neuroendocrine differentiation and other histologic components are permitted if adenocarcinoma is the predominant histologic finding). For study participants without a prior histologic diagnosis, a fresh baseline biopsy specimen must be used to confirm the diagnosis.
- 3 Metastatic prostate cancer confirmed by a positive bone scan (bone lesions) or metastatic lesions (soft tissue/visceral lesions) on CT or MRI scans. a. If no evaluable bone lesions (according to PCWG3 criteria) are present, measurable soft tissue/visceral lesions (according to RECIST v1.1) are required. b. For study participants with only measurable soft tissue lesions, those with only regional lymph node disease (i.e., lymph node disease below the aortic bifurcation) are ineligible for study entry. c. PET and SPECT are not evaluable imaging modalities for this study. d. If a bone scan shows intense, symmetrical activity in the bones (called hyperbone scintigraphy), the patient is considered ineligible.
- 4 Any acute effects of previous treatment have resolved to baseline or CTCAE ≤ Grade 1 (except for AEs that are judged by the investigator not to pose a safety risk).
- 5 Study participants cannot have received any cytotoxic chemotherapy, ARPI (e.g., enzalutamide, apalutamide, abiraterone acetate, or darolutamide), or any other systemic anticancer treatment for mCSPC, with the following exceptions: a. ADT (chemotherapy or surgery) must be started before randomization and must be continued throughout the study. Up to 3 months of previous ADT (with or without antiandrogens) is permitted, with no radiographic evidence of disease progression or elevated PSA levels before study day 1. b. Estrogen, cyproterone acetate, or first-generation antiandrogen therapy is permitted until randomization but must be discontinued before randomization. c. Study participants may have received 1 previous course of palliative radiation therapy or surgery to control secondary symptoms of prostate cancer, which should have been completed at least 2 weeks before randomization. Note: Radical prostate surgery or radical radiation therapy with curative intent for the primary prostate tumor of participants with mCSPC is not permitted.
- 6 Study participants must have an ECOG PS score of 0 or 1
- Inclusion Criteria *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. *Metastatic prostate cancer documented by positive bone scan (for bone disease) or metastatic lesion(s) on CT or MRI (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 must have ECOG PS 0 or 1.
Exclusion criteria
- Exclusion Criteria
- * 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.
- * Clinically significant cardiovascular disease.
- * Known or suspected brain metastasis or active leptomeningeal disease.
- * Participants must be treatment naive at the mCSPC stage, eg, participants cannot have received any cytotoxic chemotherapy with the following exceptions: Treatment with first-generation antiandrogen (ADT) agents is allowed for mCSPC.
- * Previous administration with an investigational product (drug or vaccine) within 30 days.
- * 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).
- * Inadequate organ function.
- CFDA
- 1Any medical or psychiatric condition that may increase the risk of study participation or (in the investigator's judgment) may make the study participant unsuitable for study participation, including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormalities. a. HIV/HBV/HCV testing is not required unless mandated by local health regulatory authorities. b. Study participants with known HIV or AIDS-related illnesses or active hepatitis B or C are excluded. Active HBV is defined as the presence of the following: HBsAg reactive or detectable HBV DNA [qualitative] Note: HBsAg(-), HBcAb(+) study participants are eligible for study participation and should be monitored/treated according to local standard of care. Active HCV is defined as: Detectable HCV RNA [qualitative] c. Exclude study participants with a known history of chronic liver disease, including alcoholic liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, Wilson's disease, hemochromatosis, alpha-1 antitrypsin deficiency, or other chronic liver diseases. d. Exclude study participants with a known history of active inflammatory gastrointestinal disease, chronic diarrhea, or a previous gastrectomy or gastric banding procedure.
- 2Any of the following within the past 6 months: myocardial infarction, severe/unstable angina, coronary artery/peripheral artery bypass grafting, symptomatic congestive heart failure (New York Heart Association class III or IV), cerebrovascular accident or symptomatic pulmonary embolism or other clinically significant thromboembolic disease, congenital long QT syndrome, torsades de pointes, clinically important arrhythmias, left anterior hemiblock (bifascicular block), sustained arrhythmias of NCI CTCAE grade 2 or higher, or other cardiovascular disease assessed by the investigator as clinically significant. Participants may be eligible if they have an implanted cardiac rhythm device/pacemaker and a QTcF > 470 ms. Screening ECG shows a QTcF > 480 ms.
- 3Central Nervous System (CNS) Pathology/Neurological Abnormalities: a. Known or suspected brain metastases or active leptomeningeal disease. b. Symptomatic or impending spinal cord compression or cauda equina syndrome. c. Participants with epidural disease, spinal canal disease, and prior spinal cord involvement are not excluded if these sites have been treated, are stable, and have no neurological impairment. d. History of clinically significant seizures or any condition that could cause seizures (e.g., previous cortical stroke, significant brain injury). In addition, unexplained loss of consciousness or transient ischemic attack within 12 months prior to randomization.
- 4Any history of myelodysplastic syndrome, acute myeloid leukemia, or any other prior malignancy, excluding any of the following: a. Carcinoma in situ or non-melanoma skin cancer. b. Any prior malignancy ≥ 3 years prior to randomization with no subsequent evidence of recurrence or progression, regardless of stage. c. Stage 0 or 1 cancer < 3 years prior to randomization with an investigator-assessed minimal probability of recurrence or progression.
- 5Any clinically significant gastrointestinal disease that the investigator believes may affect absorption.
- 6Current use of any contraindicated concomitant medications, or unwillingness or inability to use required concomitant medications. See Section 6.9. a. Current use or anticipated need for medications known to be potent inhibitors and inducers of CYP3A4/5 (except enzalutamide in this study, see Sections 6.9.1 and 6.9.2), including use within 10 days or 5 half-lives (whichever is longer) prior to randomization. b. Use of > 10 mg/day of prednisone (or equivalent) within 28 days prior to randomization is prohibited.
- 7Prior treatment: a. ADT in the adjuvant/neoadjuvant setting, with completion of ADT less than 12 months prior to randomization and a total duration of ADT greater than 36 months. b. ARPIs (e.g., abiraterone, apalutamide, darolutamide, enzalutamide) or other investigational ARPIs. c. Use of cytochrome P17 inhibitors (e.g., oral ketoconazole) as anticancer treatment for prostate cancer. d. Chemotherapy (including docetaxel) or immunotherapy for prostate cancer. e. Radiopharmaceuticals (e.g., 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 described above.
- 8Received other investigational drugs (drugs or vaccines) that do not meet exclusion criteria 7 within 30 days or 5 half-lives (whichever is longer) before the first dose of the study therapeutic intervention drug used in this study. Participated in other investigational drug (drug or vaccine) research at any time during participation in this study
- 9Insufficient renal function, defined as an eGFR < 45 mL/min/1.73 m2. Based on the study participant's age at screening, calculate eGFR using the formula recommended in Appendix 7, Section 10.7.2 to determine eligibility and serve as a baseline for quantifying any subsequent renal safety events. If eligibility is assessed based on estimated renal function, the higher of the screening and baseline eGFR values may be used.
- 10Liver dysfunction, defined as: a. Total bilirubin ≥ 1.5 times ULN (except Gilbert syndrome, in which case direct bilirubin > ULN should be excluded) b. AST > 2.5 times ULN c. ALT > 2.5 times ULN
- 11Hematologic abnormalities, defined as: a. ANC < 1500/mm3 b. Platelets < 100,000/mm3, independent of transfusion within 14 days prior to randomization c. Hemoglobin < 9 g/dL, independent of transfusion within 14 days prior to randomization
- 12Research center staff directly involved in the conduct of the study and their families, other research center staff supervised by the investigator, sponsor and sponsor representative employees directly involved in the conduct of the study and their families.
- 13Inability to swallow oral medications.
- Exclusion Criteria *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. *Clinically significant cardiovascular disease. *Known or suspected brain metastasis or active leptomeningeal disease. *Participants must be treatment naive at the mCSPC stage, eg, participants cannot have received any cytotoxic chemotherapy with the following exceptions: Treatment with first-generation antiandrogen (ADT) agents is allowed for mCSPC. *Previous administration with an investigational product (drug or vaccine) within 30 days. *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). *Inadequate organ function.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Carolinas
Myrtle Beach, SC, United States, 29572
Investigator
Neal Shore
Status
Recruiting
Condition(s) Treated at Site
Prostate