Clinical Trials /

Talazoparib With Androgen Deprivation Therapy and Abiraterone for the Treatment of Castration Sensitive Prostate Cancer

NCT04734730

Description:

This phase II trial studies the effect of talazoparib with androgen deprivation therapy and abiraterone in treating castration sensitive prostate cancer patients. Talazoparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Androgen can cause the growth of prostate tumor cells. Degarelix, leuprolide acetate, bicalutamide, goserelin acetate, and abiraterone lowers the amount of androgen made by the body. This may help stop the growth of tumor cells that need androgen to grow. Giving talazoparib with androgen deprivation therapy and abiraterone may improve cancer control for patients with castration sensitive prostate cancer.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Talazoparib With Androgen Deprivation Therapy and Abiraterone for the Treatment of Castration Sensitive Prostate Cancer
  • Official Title: Phase II Study of Talazoparib With Androgen Deprivation Therapy and Abiraterone in Castration Sensitive Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: 20476
  • SECONDARY ID: NCI-2020-10199
  • SECONDARY ID: 20476
  • SECONDARY ID: P30CA033572
  • NCT ID: NCT04734730

Conditions

  • Castration-Sensitive Prostate Carcinoma
  • Metastatic Prostate Adenocarcinoma
  • Stage IV Prostate Cancer AJCC v8
  • Stage IVA Prostate Cancer AJCC v8
  • Stage IVB Prostate Cancer AJCC v8

Interventions

DrugSynonymsArms
Abiraterone AcetateCB7630, Yonsa, ZytigaTreatment (talazoparib, androgen deprivation therapy)
BicalutamideCasodex, Cosudex, ICI 176,334, ICI 176334Treatment (talazoparib, androgen deprivation therapy)
DegarelixFE200486, FirmagonTreatment (talazoparib, androgen deprivation therapy)
Goserelin AcetateZDX, ZoladexTreatment (talazoparib, androgen deprivation therapy)
Leuprolide AcetateA-43818, Abbott 43818, Abbott-43818, Carcinil, Depo-Eligard, Eligard, Enanton, Enantone, Enantone-Gyn, Ginecrin, LEUP, Leuplin, Leuprorelin Acetate, Lucrin, Lucrin Depot, Lupron, Lupron Depot, Lupron Depot-3 Month, Lupron Depot-4 Month, Lupron Depot-Ped, Lutrate, Procren, Procrin, Prostap, TAP-144, Trenantone, Uno-Enantone, ViadurTreatment (talazoparib, androgen deprivation therapy)
Prednisone.delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-PrednisoneTreatment (talazoparib, androgen deprivation therapy)
TalazoparibBMN 673, BMN-673Treatment (talazoparib, androgen deprivation therapy)

Purpose

This phase II trial studies the effect of talazoparib with androgen deprivation therapy and abiraterone in treating castration sensitive prostate cancer patients. Talazoparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Androgen can cause the growth of prostate tumor cells. Degarelix, leuprolide acetate, bicalutamide, goserelin acetate, and abiraterone lowers the amount of androgen made by the body. This may help stop the growth of tumor cells that need androgen to grow. Giving talazoparib with androgen deprivation therapy and abiraterone may improve cancer control for patients with castration sensitive prostate cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Increase the efficacy of first-line therapy for men with metastatic castration-sensitive
      prostate cancer by adding the PARP inhibitor talazoparib to standard therapy with androgen
      deprivation therapy (ADT) + abiraterone acetate (abiraterone).

      II. Study the efficacy of abiraterone and talazoparib in an ethnically diverse population.

      III. Evaluate whether androgen receptor genetic variation may identify a subpopulation of
      patients who benefit, even in the absence of homologous repair deficiency mutations.

      OUTLINE:

      Patients receive talazoparib orally (PO) once daily (QD), abiraterone acetate PO QD, and
      prednisone PO QD on days 1-28. Patients also receive androgen deprivation therapy consisting
      of degarelix subcutaneously (SC) on day 1; leuprolide acetate intramuscularly (IM) on day 1
      and bicalutamide PO QD on days 1-28 of cycle 1 and then leuprolide acetate IM on day 1 of
      subsequent cycles; leuprolide acetate IM on day 1 and bicalutamide PO QD on days 1-28 of
      cycle 1 and then leuprolide acetate IM on day 1 of cycles 2, 5, 8, and 11; or goserelin
      acetate SC monthly or every 3 months. Cycles repeat every 28 days in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (talazoparib, androgen deprivation therapy)ExperimentalPatients receive talazoparib PO QD, abiraterone acetate PO QD, and prednisone PO QD on days 1-28. Patients also receive androgen deprivation therapy consisting of degarelix SC on day 1; leuprolide acetate IM on day 1 and bicalutamide PO QD on days 1-28 of cycle 1 and then leuprolide acetate IM on day 1 of subsequent cycles; leuprolide acetate IM on day 1 and bicalutamide PO QD on days 1-28 of cycle 1 and then leuprolide acetate IM on day 1 of cycles 2, 5, 8, and 11; or goserelin acetate SC monthly or every 3 months. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Abiraterone Acetate
  • Bicalutamide
  • Degarelix
  • Goserelin Acetate
  • Leuprolide Acetate
  • Prednisone
  • Talazoparib

Eligibility Criteria

        Inclusion Criteria:

          -  All patients must have a histologically or cytologically proven diagnosis of
             adenocarcinoma of the prostate. (Note: Gleason score not required if biopsy of
             metastasis was used to make the histologic diagnosis)

          -  All patients must have metastatic disease: either soft tissue and/or bony metastases
             prior to initiation of androgen. Measurable disease is not required

          -  Baseline imaging must have been performed within 42 days before or 14 days after
             initiating luteinizing hormone releasing hormones (LHRH) therapy. All disease must be
             assessed and documented on the Baseline Tumor Assessment Form

          -  Patients may have started on LHRH therapy for metastatic prostate cancer provided this
             was initiated no longer than 60 days prior to registration

               -  Patients may have received neoadjuvant and/or adjuvant LHRH therapy during
                  definitive treatment or salvage radiation; if so at least 12 months must have
                  elapsed from the last LHRH injection and baseline testosterone must be > 150
                  ng/dL

               -  No restriction on bicalutamide used for flare prevention or combined therapy
                  however bicalutamide must be stopped at registration

          -  Patients must have a Karnofsky performance status of 60 - 100

          -  Men of reproductive potential and those who are surgically sterilized (i.e.,
             vasectomy) must agree to practice effective barrier contraception or agree to abstain
             from intercourse while receiving treatment on this study and for at least 4 months
             after protocol treatment ends

          -  Bilirubin =< 2 x institutional upper limit of normal (ULN) (obtained within 28 days
             prior to registration)

          -  Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
             serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x
             institutional ULN, or =< 5 x institutional ULN if liver metastases are present
             (obtained within 28 days prior to registration)

          -  Calculated creatinine clearance >= 30 mL/min using a serum creatinine obtained within
             28 days prior to registration

          -  Leukocytes >= 3,000/mcL (obtained within 28 days prior to registration)

          -  Absolute neutrophil count (ANC) >= 1,500/mcL (obtained within 28 days prior to
             registration)

          -  Hemoglobin >= 9 g/dL (obtained within 28 days prior to registration)

          -  Platelets >= 100,000/mcL (obtained within 28 days prior to registration)

          -  All subjects must have the ability to understand and the willingness to sign a written
             informed consent

          -  Patients may have received prior androgen deprivation therapy (ADT) -neoadjuvant
             and/or adjuvant, or in conjunction with salvage radiation - but it must not have
             lasted for more than 36 months. Single or combination therapy allowed. At least 6
             months must have elapsed since completion of androgen deprivation therapy in the
             neoadjuvant and/or adjuvant setting, and serum testosterone must be > 150 ng/mL within
             28 days prior to registration. Note: Serum testosterone assessment is required for
             eligibility for only those with prior treatment with ADT

               -  Patients who have already started on LHRH therapy are eligible, provided no more
                  than 60 days have elapsed from LHRH injection (or surgical castration) for
                  metastatic prostate cancer prior to registration. The start date of medical
                  castration is considered the day the patient first received an injection of a
                  LHRH agonist/antagonist (or orchiectomy), not an oral antiandrogen. Subjects may
                  not already be taking abiraterone, enzalutamide, apalutamide or other
                  intensification agent during this time - bicalutamide is permitted

          -  Patients may have received palliative radiotherapy for symptomatic bone or visceral
             metastasis, provided they have recovered from all side effects at the time of
             registration

          -  Patients may have received prior surgery. For all major surgeries, at least 14days
             must have elapsed since completion and patient must have recovered from all major side
             effects of surgery per investigator's assessment

          -  Patients may have received or plan to receive concurrent bone targeting agents that do
             not have an effect on prostate specific antigen (PSA) (e.g. denosumab or
             bisphosphonate)

        Exclusion Criteria:

          -  Patients must not have received prior and/or must not have any plans for receiving
             concomitant therapy with ketoconazole, aminoglutethimide, or enzalutamide (MDV3100).
             Concurrent megestrol for hot flashes is allowed

          -  Patients must not have received any prior cytotoxic chemotherapy for metastatic
             prostate cancer

               -  Prior cytotoxic chemotherapy with curative intent in the neoadjuvant or adjuvant
                  setting may be allowed at the discretion of the principal investigator. At least
                  2 years must have elapsed since completion of cytotoxic chemotherapy in the
                  neoadjuvant and/or adjuvant setting

          -  Patients with known brain metastases are not eligible. Brain imaging studies are not
             required for eligibility if the patient has no neurologic signs or symptoms suggestive
             of brain metastasis. But, if brain imaging studies are performed, they must be
             negative for disease

          -  Patients must not have New York Heart Association class III or IV heart failure at the
             time of screening. Patients must not have any thromboembolic event, unstable angina
             pectoris, myocardial infarction, or serious uncontrolled cardiac arrhythmia within 6
             months prior to registration

          -  Patients must not have uncontrolled hypertension (defined as blood pressure > 160 mmHg
             systolic and > 90 mmHg diastolic at 2 separate measurements no more than 60 minutes
             apart) despite appropriate medical therapy. Note: Patients may be rescreened after
             adjustments of antihypertensive medications

          -  Patients must not be known to have human immunodeficiency virus (HIV) infection,
             active chronic hepatitis B or C, life-threatening illness unrelated to cancer, or any
             serious medical or psychiatric illness that could, in the investigator's opinion,
             potentially interfere with participation in this study

          -  Patients with a known history of primary and secondary adrenal insufficiency are not
             eligible

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to any of the study drugs

          -  Patients may not be receiving any other investigational agents, or concurrent
             biological, chemotherapy, or radiation therapy. Previous experimental therapy must
             have been completed at least 28 days prior to registration

          -  Patients must not have known gastrointestinal (GI) disease or GI procedure that could
             interfere with the GI absorption or tolerance of any of the study drugs, including
             difficulty swallowing oral medications

          -  No other prior malignancy is allowed except for the following: adequately treated
             basal cell or squamous cell skin cancer, adequately treated stage I or II cancer from
             which the patient is currently in complete remission, or any other cancer from which
             the patient has been disease-free for 5 years
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Prostate specific antigen (PSA) nadir < 0.2
Time Frame:At 12 months
Safety Issue:
Description:Will be estimated with 95% Clopper-Pearson interval.

Secondary Outcome Measures

Measure:Objective response rate
Time Frame:Up to 2 years
Safety Issue:
Description:Will be determined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for patients with measurable disease only, and summarized by % of patients achieving complete response, partial response, stable disease, or progressive disease as best response.
Measure:PSA responses
Time Frame:Up to 2 years
Safety Issue:
Description:Will be described by waterfall plots as recommended by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) as well as identifying the % of patients achieving a 50% and 90% reduction in PSA.
Measure:Radiographic progression-free survival (PFS)
Time Frame:Up to 2 years
Safety Issue:
Description:Will be evaluated for all patients, using RECIST for soft tissue and including the PCWG3 criteria for bone scan assessment of progression of disease. PFS will be carried out by Kaplan-Meier curve and log-rank test will be used to detect difference between groups.
Measure:Patient reported outcomes
Time Frame:Up to 2 years
Safety Issue:
Description:Will be collected using Functional Assessment of Cancer Therapy- Prostate and evaluated for changes from baseline, endpoint will be time to deterioration in quality of life.
Measure:Androgen receptor (AR) genetic variations
Time Frame:Up to 2 years
Safety Issue:
Description:The effect of AR genetic variations on PSA nadir <0.2 at 12 months, ORR, PSA response or PFS. AR CAG and GGC repeats will be analyzed as a continuous variable as well dichotomized as high versus low. PSA nadir results will be compared between CAG/GGC repeat groups.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:City of Hope Medical Center

Last Updated

February 9, 2021