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Talazoparib + Enzalutamide vs. Enzalutamide Monotherapy in mCRPC With Deoxyribonucleic Acid (DNA) Damage Repair Deficiencies (DDR)

Last updated on May 9, 2018

FOR MORE INFORMATION
Study Location
Urological Associates of Southern Arizona, PC
Tucson, Arizona, 85715 United States
Contact
1-800-718-1021
Eligibility criteria
Condition
The disease, disorder, syndrome, illness, or injury that is being studied.
mCRPC With DNA Damage Repair Deficiencies (DDR)
Sex
Male
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18+ years
Inclusion criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell
or signet cell features

Asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC)
(score on BPI-SF Question #3 must be

For enrollment into Part 2 only (optional in Part 1): DDR gene alterations (DDR+) likely to
sensitize to PARP inhibition as determined by prospective analysis (de novo or archival
tissue), or historical analysis (with Sponsor pre-approval)

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.

Bisphosphonate or denosumab dosage must have been stable for at least 4 weeks before Day 1
(Part 1) or randomization (Part 2) for patients receiving these therapies Eastern
Cooperative Oncology Group (ECOG) performance status ≤ 1.

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 pregnant woman from the time of the first
dose of study drug through 120 days after last dose of study drug. Must also agree to use
an additional highly effective form of contraception (Section 4.4.1) from the time of the
first dose of study drug through 120 days after last dose of study drug 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 120 days 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details

Any prior systemic cancer treatment initiated in the mCRPC disease state.

Patients whose only evidence of metastasis is adenopathy below the aortic bifurcation.

Prior treatment with a PARP inhibitor, cyclophosphamide, or mitoxantrone for prostate
cancer.

Prior treatment with platinum-based chemotherapy within 6 months prior to Day 1 (Part 1) or
randomization (Part 2), or any history of disease progression on platinum-based therapy at
any time in the past.

Treatment with cytotoxic chemotherapy, other hormonal therapy (eg, bicalutamide,
nilutamide, flutamide, estrogens, 5-alpha reductase inhibitors), biologic therapy including
sipuleucel-T (other than approved bone-targeting agents and GnRH agonist/antagonist
therapy), or radionuclide therapy in the 28 days prior to Day 1 (Part 1) or randomization
(Part 2).

Treatment with any investigational agent within 4 weeks or 5 half-lives of the drug
(whichever is longer) 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) unless no pain
related to prostate cancer has been reported in the 28 days prior to Day 1 (Part 1) or
randomization (Part 2).

Current or anticipated use of:

1. Medications with potential drug-drug interaction (DDI) with talazoparib: P-gp
inhibitors, P-gp inducers or BCRP inhibitors

2. Medications with potential DDI with enzalutamide: strong cytochrome P450 2C8 (CYP2C8)
inducers, strong CYP3A4 inducers, moderate CYP3A4 inducers and substrates of CYP3A4,
CYP2C9, or CYP2C19 with a narrow therapeutic index.

Major surgery (as defined by the investigator) within 2 weeks before Day 1 (Part 1) or
randomization (Part 2).

Clinically significant cardiovascular disease

Significant renal dysfunction as defined by any of the following laboratory abnormalities:

? Renal: eGFR

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

Absolute neutrophil count 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.

History of another cancer including myelodysplastic syndrome or acute myeloid leukemia
within 3 years before Day 1 (Part 1) or randomization (Part 2), with the exception of
uncomplicated nonmelanoma skin cancers, or American Joint Committee on Cancer stage 0 or
stage 1 cancer that has a remote probability of recurrence in the opinion of the
investigator and the sponsor.

Gastrointestinal disorder affecting absorption.

Fertile male subjects who are unwilling or unable to use highly effective methods of
contraception as outlined in this protocol for the duration of the study and for 120 days
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.

NCT03395197
Pfizer
Recruiting
Talazoparib + Enzalutamide vs. Enzalutamide Monotherapy in mCRPC With Deoxyribonucleic Acid (DNA) Damage Repair Deficiencies (DDR)

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Talazoparib + NHT vs. NHT Monotherapy in DDR+ mCRPC
A Phase 3, Randomized, Double-blind, Placebo-controlled Study Of Talazoparib In Combination With Physician's Choice Of Enzalutamide Or Abiraterone Acetate/Prednisone In Metastatic Castration-resistant Prostate Cancer With Dna Damage Repair Deficiencies
This study compares rPFS in men with DDR+ mCRPC treated with talazoparib plus physician's choice of novel hormonal therapy (NHT) vs. physician's choice of NHT alone after confirmation of the starting dose of talazoparib in combination with each NHT.
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 each NHT 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 physician's choice of NHT vs. placebo plus physician's choice of NHT alone in DNA damage repair-deficient (DDR+) mCRPC.
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
To assess radiographic PFS in men with DDR+ mCRPC treated with talazoparib plus physician's choice of NHT vs. placebo plus physician's choice of NHT.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Double-blind.

Primary Purpose: Treatment

DDR+ mCRPC
  • Drug: Talazoparib with NHT
    Talazoparib 1 mg/day plus either [enzalutamide 160 mg/day] or [abiraterone acetate 1000 mg/day with prednisone 5 mg twice a day]
  • Drug: Placebo with NHT
    Placebo plus either [enzalutamide 160 mg/day] or [abiraterone acetate 1000 mg/day with prednisone 5 mg twice a day]
  • Experimental: Combination arm
    Talazoparib plus physician's choice of NHT
    Intervention: Drug: Talazoparib with NHT
  • Active Comparator: Monotherapy arm
    Physician's choice of NHT.
    Intervention: Drug: Placebo with NHT
Not Provided


*   Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
444
March 17, 2024
May 30, 2022   (Final data collection date for primary outcome measure)

Inclusion Criteria:

Histologically or cytologically confirmed adenocarcinoma of the prostate.

Asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (CRPC) (score on BPI-SF Question #3 must be < 4).

For enrollment into Part 2 only (optional in Part 1): Consent to a fresh tumor biopsy before enrollment unless sufficient archival tissue (preferably of metastatic disease) is available for molecular analyses

For patients enrolling in Part 2, DNA damage repair deficiency as assessed centrally by an NGS biomarker mutation panel that contains DDR genes likely to sensitize to PARP inhibition.

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.

Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist or antagonist for patients who have not undergone bilateral orchiectomy

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 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.

Eastern Cooperative Oncology Group (ECOG) performance status ? 1.

Life expectancy ? 12 months as assessed by the investigator.

Exclusion Criteria:

Progression of metastatic CRPC while on prior treatment with taxane-based chemotherapy, or NHT initiated after onset of castration resistance. Men previously treated with NHT or taxane-based chemotherapy in the hormone sensitive prostate cancer setting or for nonmetastatic CRPC may be considered.

Treatment with cytotoxic chemotherapy, other hormonal therapy (e.g., bicalutamide, nilutamide, flutamide, estrogens, 5-alpha reductase inhibitors), biologic therapy including sipuleucel-T (other than approved bone-targeting agents and GnRH agonist/antagonist therapy), or radionuclide therapy in the 28 days prior to screening.

Treatment with any investigational agent within 4 weeks or 5 half-lives of the drug (whichever is longer) before Day 1.

Prior treatment with a PARP inhibitor, cyclophosphamide, or mitoxantrone for prostate cancer.

Prior progression on platinum-based therapy or prior treatment with platinum-based therapy within the past 6 months

Prior treatment with opioids for pain related to either primary prostate cancer or metastasis within 28 days before screening unless no pain related to prostate cancer is reported within 28 days prior to screening.

For patients the investigator chooses to receive enzalutamide, unwilling to agree to avoid the use of strong cytochrome P450 2C8 (CYP2C8) inhibitors, strong CYP3A4 inducers, or substrates of CYP3A4, CYP2C9, or CYP2C19 with a narrow therapeutic index.

For patients the investigator chooses to receive abiraterone acetate/prednisone, unwilling to agree to avoid the use of strong CYP3A4 inducers and CYP2D6 substrates with a narrow therapeutic index.

Use of a strong P-gp inhibitor (eg, dronedarone, quinidine, ranolazine, itraconazole, ketoconazole), strong P-gp inducer (eg, rifampin, tipranavir, ritonavir), or strong inhibitor of BCRP (eg, elacridar [GF120918]).

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).

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 involvement).
  • Albumin < 3.0 g/dL.

Absolute neutrophil count < 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 values at screening).

Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Gender Eligibility Description: Men at least 18 years of age. For Japan, at least 20 years of age.
18 Years and older   (Adult, Senior)
No

Contact: Pfizer CT.gov Call Center 1-800-718-1021 [email protected]
United States
 
 
NCT03395197
C3441021
2017-003295-31 ( EudraCT Number )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Yes
Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/da...
URL: http://
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
March 2018

ICMJE     Data element required by the

International Committee of Medical Journal Editors
and the
World Health Organization ICTRP

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting thte study website. To get updates and notications about this trail, sign up using the form below.

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