TALAPRO-3: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, STUDY OF TALAZOPARIB WITH ENZALUTAMIDE VERSUS PLACEBO WITH ENZALUTAMIDE IN MEN WITH DDR GENE MUTATED METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER
- Conditions
- castration sensitiveProstate cancer10038597
- Registration Number
- NL-OMON54222
- Lead Sponsor
- Pfizer
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 4
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® 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 Appendi
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 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: •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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Investigator-assessed rPFS per Response Evaluation Criteria in Solid Tumors<br /><br>(RECIST 1.1 [soft tissue disease]) and Prostate Cancer Working<br /><br>Group (PCWG3 [bone disease]) in participants with mCSPC harboring DDR<br /><br>deficiencies. </p><br>
- Secondary Outcome Measures
Name Time Method