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Talazoparib + Enzalutamide vs. Enzalutamide Monotherapy in mCRPC (TALAPRO-2)

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ClinicalTrials.gov Identifier: NCT03395197
Recruitment Status : Recruiting
First Posted : January 10, 2018
Last Update Posted : October 17, 2019
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE November 21, 2017
First Posted Date  ICMJE January 10, 2018
Last Update Posted Date October 17, 2019
Actual Study Start Date  ICMJE December 18, 2017
Estimated Primary Completion Date August 22, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 13, 2018)
  • Confirm the dose of Talazoparib (part 1) [ Time Frame: Day 1 up to 28 days ]
    determined based on the safety profile
  • Radiographic PFS (part 2) in unselected patients and in patients harboring DDR deficiencies [ Time Frame: randomization up to 25 months ]
    time from the date of randomization to first objective evidence of radiographic progression by blinded independent review, or death (occurring within 168 days of treatment discontinuation), whichever occurs first
Original Primary Outcome Measures  ICMJE
 (submitted: January 3, 2018)
  • Confirm the dose of Talazoparib for each combination treatment (part 1) [ Time Frame: Day 1 up to 28 days ]
    determined based on the safety profile
  • Radiographic PFS (part 2) [ Time Frame: randomization up to 25 months ]
    time from the date of randomization to first objective evidence of radiographic progression by blinded independent review, or death (occurring within 168 days of treatment discontinuation), whichever occurs first
Change History Complete list of historical versions of study NCT03395197 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2018)
  • Overall survival (part 2) in unselected patients and in patients harboring DDR deficiencies [ Time Frame: randomization up to 47 months ]
    time from randomization to death from any cause
  • Objective response in measurable soft tissue disease (part 2) in unselected patients and in patients harboring DDR deficiencies [ Time Frame: baseline up to 6 months ]
    proportion of patients with measurable soft tissue disease at baseline with objective response per RECIST 1.1
  • Duration of soft tissue response (part 2) in unselected patients and in patients harboring DDR deficiencies [ Time Frame: baseline up to 25 months ]
    duration of responses in patients with measurable soft tissue disease at baseline per RECIST 1.1
  • PSA response (part 2) in unselected patients and in patients harboring DDR deficiencies [ Time Frame: baseline up to 25 months ]
    proportion of patients with PSA response grater than or equal to 50%
  • Time to PSA progression (part 2) in unselected patients and in patients harboring DDR deficiencies [ Time Frame: baseline up to 25 months ]
    time from baseline to PSA progression
  • Time to initiation of cytotoxic chemotherapy (part 2) in unselected patients and in patients harboring DDR deficiencies [ Time Frame: randomization up to 47 months ]
    time from randomization to initiation of cytotoxic chemotherapy
  • Time to initiation of antineoplastic therapy (part 2) in unselected patients and in patients harboring DDR deficiencies [ Time Frame: randomization up to 47 months ]
    time from randomization to initiation of antineoplastic treatment
  • Time to first symptomatic skeletal event (part 2) in unselected patients and in patients harboring DDR deficiencies [ Time Frame: randomization up to 47 months ]
    time from randomization to first symptomatic skeletal event (symptomatic fractures, spinal cord compression, surgery or radiation to the bone whichever is first)
  • PFS on next line of therapy (PFS2) in unselected patients and in patients harboring DDR deficiencies [ Time Frame: randomization up to 47 months ]
    PFS2 based on investigator assessment
  • Opiate use for cancer pain (part 2) in unselected patients and in patients harboring DDR deficiencies [ Time Frame: randomization up to 47 months ]
    time from randomization to opiate use for prostate cancer pain
  • Incidence of adverse events (part 1 and 2) [ Time Frame: Day 1 up to 26 months ]
    AEs and SAEs incidence by type and severity (graded by NCI CTCAE version 4.03)
  • Pharmacokinetic assessment of talazoparib (part 1) [ Time Frame: Week 1, 5, 9, and 13 ]
    plasma concentration of talazoparib
  • Pharmacokinetic assessment of talazoparib (part 2) [ Time Frame: week 3, 5, 9 13, and 17 ]
    plasma concentration of talazoparib
  • Pharmacokinetic assessment of enzalutamide (part 1) [ Time Frame: week 1, 5, 9, and 13 ]
    plasma concentration of enzalutamide
  • Pharmacokinetic assessment of enzalutamide (part 2) [ Time Frame: week 3, 5, 9 13, and 17 ]
    plasma concentration of enzalutamide
  • Patient-reported outcome:pain symptoms (part 2) in unselected patients and in patients harboring DDR deficiencies [ Time Frame: baseline up to 47 months ]
    change from baseline in patient-reported pain symptoms per Brief Pain Inventory Short Form (BPI-SF)
  • Patient-reported outcome: pain symptoms (part 2) in unselected patients and in patients harboring DDR deficiencies [ Time Frame: baseline up to 47 months ]
    time to deterioration in patient-reported pain symptoms per Brief Pain Inventory Short Form (BPI-SF)
  • Patient-reported outcome: cancer specific global health status/QoL, functioning, and symptoms (part 2) in unselected patients and in patients harboring DDR deficiencies [ Time Frame: baseline up to 47 months ]
    change from baseline in patient-reported Global health status/QoL per EORTC QLQ-C30
  • Patient-reported outcome: cancer specific global health status/QoL, functioning, and symptoms (part 2) in unselected patients and in patients harboring DDR deficiencies [ Time Frame: baseline up to 47 months ]
    time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30
  • Patient-reported outcome: general health status (part2) in unselected patients and patients harboring DDR deficiencies [ Time Frame: baseline up to 47 months ]
    change from baseline in patient-reported general health status per EQ-5D-5L
  • Patient-reported outcome: general health status (part 2) in unselected patients and patients harboring DDR deficiencies [ Time Frame: baseline up to 47 months ]
    time to definitive deterioration in patient-reported disease-specific urinary symptoms per EORTC QLQ-PR25
Original Secondary Outcome Measures  ICMJE
 (submitted: January 3, 2018)
  • Overall survival (part 2) [ Time Frame: randomization up to 47 months ]
    time from randomization to death from any cause
  • Objective response rate (part 2) [ Time Frame: baseline up to 6 months ]
    proportion of patients with measurable soft tissue disease at baseline with objective response per RECIST 1.1
  • Duration of soft tissue response (part 2) [ Time Frame: baseline up to 25 months ]
    duration of responses in patients with measurable soft tissue disease at baseline per RECIST 1.1
  • PSA progression (part 2) [ Time Frame: baseline up to 25 months ]
    time from baseline to PSA progession
  • PSA response (part 2) [ Time Frame: baseline up to 25 months ]
    proportion of patients with PSA response grater than or equal to 50%
  • Initiation of cytotoxic chemotherapy (part 2) [ Time Frame: randomization up to 47 months ]
    time from randomization to initiation of cytotoxic chemotherapy
  • First symptomatic skeletal event (part 2) [ Time Frame: randomization up to 47 months ]
    time from randomization to first symptomatic skeletal event (symptomatic fractures, spinal cord compression, surgery or radiation to the bone whichever is first)
  • Initiation of antineoplastic therapy (part 2) [ Time Frame: randomization up to 47 months ]
    time from randomization to initiation of antineoplastic treatment
  • No longer clinically benefiting (part 2) [ Time Frame: randomization up to 25 months ]
    time from randomization to the date treatment is permanently discontinued for the reason "no longer clinically benefiting" in the opinion of the investigator
  • Opiate use for cancer pain (part 2) [ Time Frame: randomization up to 47 months ]
    time from randomization to opiate use for prostate cancer pain
  • Incidence of adverse events (part 1 and 2) [ Time Frame: Day 1 up to 26 months ]
    AEs and SAEs incidence by type and severity (graded by NCI CTCAE version 4.0)
  • Patient-reported outcome:pain symptoms (part 2) [ Time Frame: baseline up to 47 months ]
    change from baseline in patient-reported pain symptoms per Brief Pain Inventory Short Form (BPI-SF)
  • Patient-reported outcome: pain symptoms (part 2) [ Time Frame: baseline up to 47 months ]
    time to deterioration in patient-reported pain symptoms per Brief Pain Inventory Short Form (BPI-SF)
  • Patient-reported outcome: cancer specific global health status/QoL, functioning, and symptoms (part 2) [ Time Frame: baseline up to 47 months ]
    time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30
  • Patient-reported outcome: cancer specific global health status/QoL, functioning, and symptoms (part 2) [ Time Frame: baseline up to 47 months ]
    time to definitive deterioration in patient-reported disease-specific urinary symptoms per EORTC QLQ-PR25
  • Patient-reported outcome: cancer specific global health status/QoL, functioning, and symptoms (part 2) [ Time Frame: baseline up to 47 months ]
    change from baseline in patient-reported cancer-specific Global health status/QoL, functioning, and symptoms per EORTC QLQ-C30
  • Patient-reported outcome: general health status (part 2) [ Time Frame: baseline up to 47 months ]
    change from baseline in patient-reported general health status per EQ-5D-5L
  • Pharmacokinetic assessment of talazoparib (part 1) [ Time Frame: Week 1, 5, 9, 13 and 17 ]
    plasma concentration of talazoparib
  • Pharmacokinetic assessment of talazoparib (part 2) [ Time Frame: week 1, 5, 13 and 17 ]
    plasma concentration of talazoparib
  • Pharmacokinetic assessment of enzalutamide (part 1) [ Time Frame: week 1, 5, 9, 13 and 17 ]
    plasma concentration of enzalutamide
  • Pharmacokinetic assessment of enzalutamide (part 2) [ Time Frame: week 1, 5, 13 and 17 ]
    plasma concentration of enzalutamide
  • Pharmacokinetic assessment of abiraterone (part 1) [ Time Frame: week 1, 5, 9, 13 and 17 ]
    plasma concentration of abiraterone
  • Pharmacokinetic assessment of abiraterone (part 2) [ Time Frame: week 1, 5, 13 and 17 ]
    plasma concentration of abiraterone
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
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 for the following:

  • Carcinoma in situ or non melanoma skin cancer
  • A cancer diagnosed and treated ≥ 5 years before randomization with no subsequent evidence of recurrence
  • 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 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 Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Chile,   Czechia,   Finland,   France,   Germany,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   New Zealand,   Norway,   Peru,   Poland,   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/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Astellas Pharma Inc
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date October 2019

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