Study of Talazoparib With Enzalutamide in Men With DDR Gene Mutated metastatic castration-sensitive prostate cancer (mCSPC)
- Conditions
- Health Condition 1: C61- Malignant neoplasm of prostate
- Registration Number
- CTRI/2021/12/038776
- Lead Sponsor
- Pfizer Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 0
1. Male participants at least 18 years of age at screening.
2. Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell or signet cell features. If the participant does not have a prior histological diagnosis, a baseline de novo biopsy must be used to confirm the diagnosis and may also be used to support biomarker analysis.
3. Confirmation of DDR gene mutation status by prospective or historical analysis (with sponsor pre-approval) of blood (liquid biopsy) and/or de novo or archival tumor tissue using FoundationOne Liquid CDx or FoundationOne CDx.
4. Willing to provide tumor tissue when available (de novo or archived) for retrospective molecular profiling analysis, if not already provided as part of inclusion criterion 3.
5. Unless prohibited by local regulations or ethics committee decision, consent to a saliva sample collection for retrospective sequencing of the same DDR genes tested on tumor tissue and blood (liquid biopsy), or a subset thereof, and to serve as a germline control in identifying tumor mutations.
6. Surgically or medically castrated, with serum testosterone less or equal to 50 ng/dL (less or equal to 1.73 nmol/L) at screening. Ongoing ADT with a GnRH agonist or antagonist for participants who have not undergone bilateral orchiectomy must be initiated at least 4 weeks before randomization and must continue throughout the study.
7. Metastatic prostate cancer documented by positive bone scan (for bone disease) or metastatic lesions on CT or MRI scan (for soft tissue). Participants whose disease spread is limited to regional pelvic lymph nodes are not eligible. Note: a finding of superscan at baseline is exclusionary.
8. Prior docetaxel therapy for mCSPC (up to 6 cycles) is allowed (must be completed 2 weeks prior to randomization and all toxicities from treatment have resolved).
9. Treatment with estrogens, cyproterone acetate, or first-generation anti-androgens is allowed until randomization.
10. Other prior therapy allowed for mCSPC; <=6 months of ADT and <=3 months of approved NHT in mCSPC (ie, abiraterone + prednisone, apalutamide, or enzalutamide), if required prior to randomization.
1. Other acute or chronic medical (concurrent disease, infection or co-morbidity) or psychiatric condition including recent (within the past year) or active suicidal ideation or laboratory abnormality that interferes with a participants ability to participate in the study, may increase the risk of associated with study participation or study treatment administration, or may interfere with the interpretation of study results, and, in the investigators judgment, make the participant inappropriate for entry into the study.
2. History of seizure or any condition (as assessed by investigator) that may predispose to seizure (eg, prior cortical stroke, significant brain trauma), including any history of loss of consciousness or transient ischemic attack within 12 months of randomization.
3. Major surgery (as defined by the investigator) within 2 weeks before randomization.
4. Known or suspected brain metastasis or active leptomeningeal disease.
5. Symptomatic or impending spinal cord compression or cauda equina syndrome.
6. Any history of MDS, AML, or prior malignancy except for the following:
(a) Carcinoma in situ or non-melanoma skin cancer.
(b) A cancer diagnosed and treated greater than or equal to 3 years before randomization with no subsequent evidence of recurrence.
(c) American Joint Committee on Cancer Stage 0 or Stage 1 cancer less than 3 years before randomization that has a remote probability of recurrence in the opinion of the investigator and the sponsor.
7. In the opinion of the investigator, any clinically significant gastrointestinal disorder affecting absorption.
8. Clinically significant cardiovascular disease, including any of the following:
(a) Myocardial infarction or symptomatic cardiac ischemia within 6 months before randomization.
(b) Congestive heart failure New York Heart Association class III or IV.
(c) History of clinically significant ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes) within 1 year before screening.
(d) History of Mobitz II second degree or third-degree heart block unless a permanent pacemaker is in place.
(e) Hypotension as indicated by systolic blood pressure less than 86 mm Hg at screening.
(f) Bradycardia as indicated by a heart rate of less than 45 beats per minute on the screening electrocardiogram.
(g) Uncontrolled hypertension as indicated by systolic blood pressure greater than 170 mm Hg or diastolic blood pressure greater than 105 mm Hg at screening. However, participants can be rescreened after adequate control of blood pressure is achieved.
9. Active COVID-19 infection detected by viral test or based on clinical diagnosis (as assessed by investigator). Asymptomatic participants with no active COVID-19 infection detected but positive antibody tests, indicating past infection are allowed.
10. Prior ADT in the adjuvant/neoadjuvant setting, where the completion of ADT was less than 12 months prior to randomization and the total duration of ADT exceeded 36 months.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method radiological Progression-Free Survival - time from the date of randomization to first objective evidence of radiographic progression or death, whichever occurs first <br/ ><br>Timepoint: Time Frame: randomization up to 3 years <br/ ><br>
- Secondary Outcome Measures
Name Time Method Duration of response in measurable soft tissue disease-duration of responses in patients with measurable soft tissue disease at baseline per RECIST 1.1Timepoint: Time Frame: randomization up to 3 years;Objective response in measurable soft tissue disease-proportion of patients with measurable soft tissue disease at baseline with objective response per RECIST 1.1Timepoint: Time Frame: randomization up to 3 years;Overall Survival-time from randomization to death from any causeTimepoint: Time Frame: randomization up to 4 years;Prostate Specific Antigen (PSA) response - proportion of patients with PSA response grater than or equal to 50%Timepoint: Time Frame: randomization up to 3 years;Time to initiation of antineoplastic therapy - Time from randomization to initiation of antineoplastic therapyTimepoint: Time Frame: randomization up to 3 years;Time to PSA progression - time from baseline to PSA progressionTimepoint: Time Frame: randomization up to 3 years