Talazoparib + Enzalutamide vs. Enzalutamide Monotherapy in mCRPC

  • STATUS
    Recruiting
  • End date
    Nov 25, 2024
  • participants needed
    1037
  • sponsor
    Pfizer
Updated on 1 August 2021
Investigator
Pfizer CT.gov Call Center
Primary Contact
Florida Cancer Specialists (2.2 mi away) Contact
+502 other location

Summary

This study compares rPFS in men with mCRPC treated with talazoparib plus enzalutamide vs. enzalutamide after confirmation of the starting dose of talazoparib in combination with enzalutamide.

Description

Part 1 is an open-label, non-randomized, safety and PK run-in study designed to confirm the starting dose of talazoparib in combination with enzalutamide through assessment of target safety events and PK at select sites. Part 2 is a randomized, double-blind, placebo-controlled, multinational study comparing talazoparib plus enzalutamide vs. placebo plus enzalutamide in patients with mCRPC.

Details
Condition mCRPC, DDR+ mCRPC, DDR+ mCRPC, mCRPC With DNA Damage Repair Deficiencies (DDR), mCRPC With DNA Damage Repair Deficiencies (DDR), mCRPC With DNA Damage Repair Deficiencies (DDR), mCRPC With DNA Damage Repair Deficiencies (DDR), mCRPC With DNA Damage Repair Deficiencies (DDR), mCRPC With DNA Damage Repair Deficiencies (DDR)
Treatment Talazoparib with NHT, Placebo with NHT, Talazoparib with enzalutamide, Placebo with enzalutamide
Clinical Study IdentifierNCT03395197
SponsorPfizer
Last Modified on1 August 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Histologically or cytologically confirmed adenocarcinoma of the prostate
withoutsmall cell or signet cell features
Asymptomatic or mildly symptomatic metastatic castration resistant prostate
cancer (mCRPC) (score on BPI-SF Question #3 must be < 4)
For enrollment into Part 2 only (optional in Part 1): assessment of DDR
mutation status
Consent to a saliva sample collection for a germline comparator unless
prohibited by local regulations or ethics committee decision (optional for
patients in Part 1)
Surgically or medically castrated, with serum testosterone 50 ng/dL ( 1.73
nmol/L) at screening
Metastatic disease in bone documented on bone scan or in soft tissue
documented on CT/MRI scan
Progressive disease at study entry in the setting of medical or surgical
castration as defined by 1 or more of the following 3 criteria
Prostate specific antigen (PSA) progression defined by a minimum of 2 rising PSA values from 3 consecutive assessments with an interval of at least 7 days between assessments
Soft tissue disease progression as defined by RECIST 1.1
Bone disease progression defined by Prostate Cancer Working Group 3 (PCWG3) with 2 or more new metastatic bone lesions on a whole body radionuclide bone scan
Ongoing bisphosphonate or denosumab use prior to Day 1 (Part 1) or
randomization (Part 2) is allowed but not mandatory
Eastern Cooperative Oncology Group (ECOG) performance status 1
Life expectancy 12 months as assessed by the investigator
Able to swallow the study drug and have no known intolerance to study drugs or
excipients
Must agree to use a condom when having sex with a partner from the time of the
first dose of study drug through 4 months after last dose of study treatment
Must also agree for female partner of childbearing potential to use an
additional highly effective form of contraception from the time of the first
dose of study treatment through 4 months after last dose of study treatment
when having sex with a non pregnant female partner of childbearing potential
Must agree not to donate sperm from the first dose of study drug to 4 months
after the last dose of study drug
Evidence of a personally signed and dated informed consent document (and
molecular prescreening consent if appropriate) indicating that the patient [or
a legally acceptable representative/legal guardian] has been informed of all
pertinent aspects of the study
Willing and able to comply with scheduled visits, treatment plan, laboratory
tests, and other study procedures

Exclusion Criteria

Any prior systemic cancer treatment initiated in in the non metastatic CRPC
and mCRPC disease state
Patients whose only evidence of metastasis is adenopathy below the aortic
bifurcation
Prior treatment with second-generation androgen receptor inhibitors
(enzalutamide, apalutamide, and darolutamide), a PARP inhibitor
cyclophosphamide, or mitoxantrone for prostate cancer
Prior treatment with platinum-based chemotherapy within 6 months (from the
last dose) prior to Day 1 (Part 1) or randomization (Part 2), or any history
of disease progression on platinum-based therapy within 6 months (from the
last dose)
Treatment with cytotoxic chemotherapy, biologic therapy including sipuleucel
T, or radionuclide therapy received in the castration-sensitive prostate
cancer is NOT exclusionary if discontinued in the 28 days prior to Day 1 (Part
) or randomization (Part 2)
Treatment with any investigational agent within 4 weeks before Day 1 (Part 1)
or randomization (Part 2)
Prior treatment with opioids for pain related to either primary prostate
cancer or metastasis within 28 days prior to Day 1 (Part 1) or randomization
(Part 2)
Current use of potent P-gp inhibitors within 7 days prior to Day 1 (Part 1) or
randomization (Part 2)
Major surgery (as defined by the investigator) within 2 weeks before Day 1
(Part 1) or randomization (Part 2), or palliative localized radiation therapy
within 3 weeks before randomization (Part 2)
Clinically significant cardiovascular disease
Significant renal dysfunction as defined by any of the following laboratory
abnormalities
Renal: eGFR < 30 mL/min/1.73 m2 by the MDRD equation (available via
[www.mdrd.com](http://www.mdrd.com/))
Patients enrolled in Part 1 only: Moderate renal impairment (eGFR 30-59
mL/min/1.73 m2) at screening
Significant hepatic dysfunction as defined by any of the following laboratory
abnormalities on screening labs
Total serum bilirubin >1.5 times the upper limit of normal (ULN) (>3 ULN for patients with documented Gilbert syndrome or for whom indirect bilirubin concentrations suggest an extrahepatic source of elevation)
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 times ULN (>5 ULN if liver function abnormalities are due to hepatic metastasis)
Albumin <2.8 g/dL
Absolute neutrophil count < 1500/L, platelets < 100,000/L, or hemoglobin < 9
g/dL (may not have received growth factors or blood transfusions within 14
days before obtaining the hematology values at screening)
Known or suspected brain metastasis or active leptomeningeal disease
Symptomatic or impending spinal cord compression or cauda equina syndrome
Any history of myelodysplastic syndrome, acute myeloid leukemia, or prior
malignancy except any of the following
Carcinoma in situ or non melanoma skin cancer
Any prior malignancies 3 years before randomization with no subsequent evidence of recurrence or progression regardless of the stage
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
Gastrointestinal disorder affecting absorption
Fertile male subjects who are unwilling or unable to use highly effective
methods of contraception for the duration of the study and for 4 months after
the last dose of investigational product
Investigator site staff members directly involved in the conduct of the study
and their family members, site staff members otherwise supervised by the
investigator, or patients who are Pfizer employees, including their family
members, directly involved in the conduct of the study
Other acute or chronic medical (concurrent disease, infection, or comorbidity)
or psychiatric condition including recent (within the past year) or active
suicidal ideation or behavior or laboratory abnormality that interferes with
ability to participate in the study, may increase the risk associated with
study participation or investigational product administration, or may
interfere with the interpretation of study results and, in the judgment of the
investigator, would make the patient inappropriate for entry into this study
History of seizure or any condition that may predispose to seizure (eg, prior
cortical stroke, significant brain trauma). Also, history of loss of
consciousness or transient ischemic attack within 12 months of randomization
(Part 2)
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