Phase 3 Randomized Study of Talazoparib with Enzalutamide in Men with DDR Gene Mutated mCSPC

Phase 1

• Conditions: Metastatic Castration-sensitive Prostate Cancer; MedDRA version: 21.1Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-000248-23-SK
• Lead Sponsor: Pfizer Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-05-06
• Last Update Posted: 18 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 599

Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1.Male participants at least 18 years of age at screening (Refer to
Appendix 9 of the protocol for Japan and Republic of Korea) .
Type of Participant and Disease Characteristics:
2.Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, 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 (as per the genes included in DDR12 panel described in Table 6) 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. Ongoing ADT with a GnRH agonist or antagonist for participants who have not undergone bilateral orchiectomy must be initiated 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.
Allowed Prior Treatments:
8.Note: prior treatment of mCSPC with docetaxel is no longer permitted.
9.Treatment with estrogens, cyproterone acetate, or first-generation anti-androgens is allowed until randomization.
10.Other prior therapy allowed for mCSPC; =3 months of ADT (chemical or surgical) with or without approved NHT in mCSPC (ie, abiraterone + prednisone, apalutamide, or enzalutamide), if required prior to randomization with no radiographic evidence of disease progression or
rising PSA levels prior to Day 1.
11.Participant may have received palliative radiation or surgery for symptomatic control secondary to prostate cancer, which should have been completed at least 2 weeks prior to randomization.
12.ECOG performance status 0 or 1 (see Appendix 11 of the protocol).
13.Adequate organ function within 28 days before the first study treatment on Day 1, defined by the following:
•ANC =1500/µL, platelets =100,000/µL, or hemoglobin =9 g/dL (may not have received growth factors or blood transfusions within 14 days before obtaining the hematology laboratory tests at screening).
•Total serum bilirubin <1.5 × ULN (<3 × ULN for participants with documented Gilbert syndrome or for whom indirect bilirubin concentrations suggest an extrahepatic source of elevation).
•AST or ALT <2.5 × ULN (<5 × ULN if liver function abnormalities are due to hepatic metastasis).
•Albumin >2.8 g/dL.
•eGFR =30 mL/min/1.73 m2 by the MDRD equation, see Appendix 10 of the protocol).
14.Sexually active participants that in the opinion of the investigator are capable of ejaculating, must agree to use a condom when having

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1.Other acute or chronic medical [concurrent disease, infection, including chronic stable HIV, HBV, or HCV infection (refer to Appendix 13 of the protocol), or co-morbidity] or psychiatric condition including recent (within the past year) or active suicidal ideation/behaviour or laboratory abnormality that interferes with a participant's 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 investigator's judgment, make the participant inappropriate for entry into the study. HIV/HBV/HCV testing is not required unless mandated by local health authority.
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 4 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:
•Carcinoma in situ or non-melanoma skin cancer.
•A cancer diagnosed and treated =3 years before randomization with no subsequent evidence of recurrence.
•American Joint Committee on Cancer Stage 0 or Stage 1 cancer <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:
•Myocardial infarction or symptomatic cardiac ischemia within 6 months before randomization.
•Congestive heart failure New York Heart Association class III or IV.
•History of clinically significant ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes) within 1 year before screening.
•History of Mobitz II second degree or third-degree heart block unless a permanent pacemaker is in place.
•Hypotension as indicated by systolic blood pressure <86 mm Hg at screening.
•Bradycardia as indicated by a heart rate of <45 beats per minute on the screening electrocardiogram.
•Uncontrolled hypertension as indicated by systolic blood pressure >170 mm Hg or diastolic blood pressure >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.
Prior/Concomitant Therapy:
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.
11.Participant received treatment with systemic glucocorticoids greater than the equivalent of 10 mg per day of prednisone within 4 weeks prior to randomization, intended for the treatment of prostate cancer.
12.Any previous treatment with DNA-damaging cytotoxic chemothera

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified