Talazoparib + Enzalutamide vs. Enzalutamide Monotherapy in mCRPC

NCT03395197

Last updated date
Study Location
Rush University Medical Center Professional Office Building Infusion Pharmacy
Chicago, Illinois, 60612, United States

Study Website

Contact a representative by phone, email, or visiting the study website. Please see the references below:

By phone

Pfizer Clinical Trials Contact Center

1-800-718-1021

By email

Contact

[email protected]

Call Now

Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
mCRPC
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 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


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 1) 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).


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/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).


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).

NEED INFO?

For Patients: Please visit the study website for more information

All other inquiries: Questions about a trial? Call or email to reach a Pfizer Clinical Trial Contact Center Representative

Pfizer Clinical Trials Contact Center

1-800-718-1021

[email protected]

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mCRPCTalazoparib + Enzalutamide vs. Enzalutamide Monotherapy in mCRPC
NCT03395197
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Male
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Talazoparib + Enzalutamide vs. Enzalutamide Monotherapy in mCRPC
Official Title  ICMJE A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF TALAZOPARIB WITH ENZALUTAMIDE IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER
Brief 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.
Detailed 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
To assess radiographic PFS in men with mCRPC (with no systemic treatments initiated after documentation of mCRCP) treated with talazoparib and enzalutamide vs. placebo plus enzalutamide
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double-blind.
Primary Purpose: Treatment
Condition  ICMJE mCRPC
Intervention  ICMJE
  • Drug: Talazoparib with enzalutamide
    Talazoparib 0.5 mg/day plus enzalutamide 160mg/day
  • Drug: Placebo with enzalutamide
    Placebo plus enzalutamide 160 mg/day
Study Arms  ICMJE
  • Experimental: Combination arm
    Talazoparib plus enzalutamide
    Intervention: Drug: Talazoparib with enzalutamide
  • Active Comparator: Monotherapy arm
    Ezalutamide plus placebo
    Intervention: Drug: Placebo with enzalutamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 3, 2019)
1037
Original Estimated Enrollment  ICMJE
 (submitted: January 3, 2018)
444
Estimated Study Completion Date  ICMJE November 25, 2024
Estimated Primary Completion Date August 22, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 1) 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).

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/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).

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).

Sex/Gender  ICMJE
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.
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center1-800-718-1021[email protected]
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Canada,   Chile,   China,   Czechia,   Finland,   France,   Germany,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   New Zealand,   Norway,   Peru,   Poland,   Portugal,   South Africa,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03395197
Other Study ID Numbers  ICMJE C3441021
2017-003295-31 ( EudraCT Number )
TALAPRO-2 ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:Yes
Plan Description:Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d….
URL:https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d…
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Astellas Pharma Inc
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS Account Pfizer
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP