Clinical Trials /

A Study of Talazoparib in Men With DNA Repair Defects and Metastatic Castration-Resistant Prostate Cancer

NCT03148795

Description:

The purpose of this international, phase 2, open-label, response rate study of talazoparib is to assess the efficacy and safety of talazoparib in men with DNA repair defects metastatic castration-resistant prostate cancer (CRPC) who previously received taxane-based chemotherapy and progressed on at least 1 novel hormonal agent (enzalutamide and/or abiraterone acetate/prednisone).

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Talazoparib in Men With DNA Repair Defects and Metastatic Castration-Resistant Prostate Cancer
  • Official Title: Talapro-1: A Phase 2, Open Label, Response Rate Study Of Talazoparib In Men With Dna Repair Defects And Metastatic Castration Resistant Prostate Cancer Who Previously Received Taxane Based Chemotherapy And Progressed On At Least 1 Novel Hormonal Agent (Enzalutamide And/or Abiraterone Acetate/Prednisone)

Clinical Trial IDs

  • ORG STUDY ID: MDV3800-06
  • SECONDARY ID: C3441006
  • SECONDARY ID: 2016-002036-32
  • NCT ID: NCT03148795

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
TalazoparibMDV3800Talazoparib

Purpose

The purpose of this international, phase 2, open-label, response rate study of talazoparib is to assess the efficacy and safety of talazoparib in men with DNA repair defects metastatic castration-resistant prostate cancer (CRPC) who previously received taxane-based chemotherapy and progressed on at least 1 novel hormonal agent (enzalutamide and/or abiraterone acetate/prednisone).

Trial Arms

NameTypeDescriptionInterventions
TalazoparibExperimentalTalazoparib 1 mg daily
  • Talazoparib

Eligibility Criteria

        Inclusion Criteria:

          1. At least 18 years of age.

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

          3. Patients must have measurable soft tissue disease per RECIST 1.1

          4. DNA damage repair deficiency as assessed centrally by a gene mutation biomarker panel
             (testing of de novo or archiaval tumor tissue (via central laboratory) or prior
             historical testing (with Sponsor approval) using the Foundation Medicine,
             FoundationOne® NGS gene panel test.

          5. Consent to a saliva sample collection for a germline comparator, unless prohibited by
             local regulations or ethics committee (EC) decision.

          6. Serum testosterone ≤ 1.73 nmol/L (50 ng/dL) at screening.

          7. Bilateral orchiectomy or ongoing androgen deprivation therapy with a
             gonadotropin-releasing hormone (GnRH) agonist/antagonist (surgical or medical
             castration).

          8. Progressive disease at study entry defined as 1 or more of the following 3 criteria:

               -  A minimum of 3 rising PSA values with an interval of at least 1 week between
                  determinations. The screening central laboratory PSA value must be ≥ 2 μg/L (2
                  ng/mL) if qualifying solely by PSA progression.

               -  Soft tissue disease progression as defined by RECIST 1.1.

               -  Bone disease progression defined by PCWG3 with 2 or more new metastatic lesions
                  on bone scan.

          9. Metastatic disease.

         10. Previous treatment with 1 or 2 chemotherapy regimens including at least 1 taxane-based
             regimen for metastatic (non castrate or castrate) prostate cancer. Patients may have
             received radium-223 and/or cabazitaxel, or were deemed unsuitable, declined, or did
             not have access to these therapies.

         11. Documented disease progression (either radiographic or biochemical) on at least 1
             novel hormonal therapy (enzalutamide and/or abiraterone acetate/prednisone) for the
             treatment of metastatic CRPC, irrespective of prior NHT treatment for non castrate
             prostate cancer or nonmetastatic (M0) CRPC.

         12. Bisphosphonate or denosumab dosage must have been stable for at least 4 weeks before
             day 1 for patients receiving these therapies.

         13. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

         14. Estimated life expectancy of ≥ 6 months as assessed by the investigator.

         15. Able to swallow the study drug, have no known intolerance to study drugs or
             excipients, and comply with study requirements.

         16. Must use a condom when having sex with a pregnant woman from the time of the first
             dose of study drug through 105 days after last dose of study drug. An additional
             highly effective form of contraception must be used from the time of the first dose of
             study drug through 105 days after last dose of study drug when having sex with a non
             pregnant female partner of childbearing potential.

         17. Must agree not to donate sperm from the first dose of study drug to 105 days after the
             last dose of study drug.

         18. Patients must be willing and able to comply with scheduled visits, treatment plan,
             laboratory tests and other study procedures.

        Exclusion Criteria:

          1. 1. Use of systemic chemotherapeutic (including but not limited to taxanes), hormonal,
             biologic, or radionuclide therapy for treatment of metastatic prostate cancer (other
             than approved bone targeting agents and GnRH agonist/antagonist) or any other
             investigational agent within 4 weeks before day 1.

          2. Prior treatment with a PARP inhibitor, cyclophosphamide, or mitoxantrone chemotherapy.
             Patients who discontinued prior platinum based chemotherapy <=6 months prior to
             screening or whose disease previously progressed on platinum based therapy at any time
             in the past are also excluded.

          3. Treatment with any concurrent cytotoxic chemotherapy or investigational drug(s) within
             4 weeks or 5 half lives of the drug (whichever is longer) before Day 1 and/or during
             study participation

          4. Radiation therapy within 3 weeks (within 2 weeks, if single fraction of radiotherapy)
             before day 1.

          5. Major surgery within 2 weeks before day 1.

          6. Clinically significant cardiovascular disease.

          7. Significant renal, hepatic, or bone marrow organ dysfunction.

          8. Known or suspected brain metastasis or active leptomeningeal disease.

          9. Symptomatic or impending spinal cord compression or cauda equina syndrome.

         10. Diagnosis of MDS (Myelodysplastic syndromes).

         11. History of another cancer within 3 years before enrollment with the exception of
             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.

         12. Gastrointestinal disorder affecting absorption.

         13. Current or anticipated use of the following P gp inhibitors (amiodarone, carvedilol,
             clarithromycin, cobicistat, darunavir, dronedarone, erythromycin, indinavir,
             itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine,
             ritonavir, saquinavir, telaprevir, tipranavir, verapamil, and valspodar), P gp
             inducers (avasimibe, carbamazepine, phenytoin, rifampin, and St. John's wort), or BCRP
             inhibitors (curcumin, cyclosporine, elacridar [GF120918] and eltrombopag).

         14. Any other acute or chronic medical or psychiatric condition (concurrent disease,
             infection, or comorbidity) that interferes with ability to participate in the study,
             causes undue risk, or complicates the interpretation of data, in the opinion of the
             investigator or medical monitor, including recent (within the past year) or active
             suicidal ideation or behavior or laboratory abnormality that 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.

         15. 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.

         16. Fertile male subjects who are unwilling or unable to use a highly effective method of
             contraception as outlined in this protocol for the duration of the study and for at
             least 105 days after the last dose of investigational product.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Anticipated in about 34 months following first patient enrolled
Safety Issue:
Description:The best ORR is defined as the proportion of patients with a best overall soft tissue response of CR (complete response) or PR (partial response) per RECIST 1.1 by independent central review.

Secondary Outcome Measures

Measure:Time to objective response
Time Frame:Anticipated in about 34 months following first patient enrolled
Safety Issue:
Description:The time from enrollment to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3.
Measure:Duration of response
Time Frame:Anticipated in about 34 months following first patient enrolled
Safety Issue:
Description:The duration of response is defined as the time from the first objective evidence of soft tissue response (subsequently confirmed) per RECIST 1.1 by independent central review and no evidence of confirmed bone disease progression per PCWG3 (the Prostate Cancer Clinical Trials Working Group 3) to the first subsequent objective evidence of radiographic progression or death due to any cause, whichever occurs first.
Measure:Proportion of patients with prostate-specific antigen (PSA) response ≥ 50%
Time Frame:Anticipated in about 34 months following first patient enrolled
Safety Issue:
Description:PSA response will be calculated as a decline from baseline PSA (ng/mL) to the maximal PSA response with a threshold of 50%.
Measure:Proportion of patients with conversion of circulating tumor cell (CTC) count
Time Frame:Anticipated in about 34 months following first patient enrolled
Safety Issue:
Description:The CTC count conversion rate will be defined as the proportion of patients with a CTC count ≥ 5 CTC per 7.5 mL of blood at study entry that decreases to < 5 CTC per 7.5 mL of blood anytime on study. In addition, proportion of patients with a CTC count of 1 or more (detectable) per 7.5 mL of blood at study entry that decreases to CTC=0 (undetectable) per 7.5 mL of blood any time on study
Measure:Time to PSA progression
Time Frame:Anticipated in about 34 months following first patient enrolled
Safety Issue:
Description:The time to PSA progression is defined as the time from enrollment to the date that a ≥ 25% increase in PSA with an absolute increase of ≥ 2 μg/L (2 ng/mL) above the nadir (or baseline for patients with no PSA decline) is documented, confirmed by a second consecutive PSA value obtained ≥ 3 weeks (21 days) later.
Measure:Radiographic progression-free survival (PFS)
Time Frame:Anticipated in about 34 months following first patient enrolled
Safety Issue:
Description:Radiographic PFS is defined as the time from enrollment to radiographic progression in soft tissue per RECIST 1.1 by independent central review, in bone per PCWG3 by independent central review, or death on study (defined as death within 168 days of study drug discontinuation without evidence of radiographic progression), whichever occurs first.
Measure:Overall survival
Time Frame:Anticipated in about 34 months following first patient enrolled
Safety Issue:
Description:Overall survival is defined as the time from enrollment to death due to any cause.
Measure:Patient-reported pain as assessed by the Brief Pain Inventory Short Form (BPI-SF)
Time Frame:Anticipated in about 34 months following first patient enrolled
Safety Issue:
Description:Patient-reported pain assessed by the BPI-SF will be summarized descriptively by study visit.
Measure:Patient-reported health-related quality of life as assessed by the European Quality of Life 5-Domain 5-Level Scale (EQ-5D-5L)
Time Frame:Anticipated in about 34 months following first patient enrolled
Safety Issue:
Description:Patient-reported health-related quality of life assessed by the EQ-5D-5L will be summarized descriptively.
Measure:Safety as assessed by percentage of patients with any Adverse Event (AE), AE leading to Study Drug Discontinuation, AE leading to death, Serious Adverse Event (SAE), AE related to study drug, SAE related to study drug
Time Frame:Anticipated in about 34 months following first patient enrolled
Safety Issue:
Description:All safety analyses will be performed using the safety population, defined as all patients in the ITT population who receive any amount of any study drug.
Measure:Pharmacokinetics (PK) of talazoparib as assessed by trough plasma concentrations
Time Frame:Anticipated in about 34 months following first patient enrolled
Safety Issue:
Description:PK data analyses will include descriptive summary statistics of the predose Cmin and postdose concentrations of talazoparib by study visit for each treatment group.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pfizer

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