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

NCT ID: NCT04734730

Last Updated: 2025-01-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-04
• Study Completion Date: 2027-08-23

Brief Summary

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (talazoparib, androgen deprivation therapy)

Patients 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.

Group Type: EXPERIMENTAL

Abiraterone Acetate

Intervention Type: DRUG

Given PO

Bicalutamide

Intervention Type: DRUG

Given PO

Degarelix

Intervention Type: DRUG

Given SC

Goserelin Acetate

Intervention Type: DRUG

Given SC

Leuprolide Acetate

Intervention Type: DRUG

Given IM

Prednisone

Intervention Type: DRUG

Given PO

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Talazoparib

Intervention Type: DRUG

Given PO

Interventions

Abiraterone Acetate

Given PO

Intervention Type: DRUG

Bicalutamide

Given PO

Intervention Type: DRUG

Degarelix

Given SC

Intervention Type: DRUG

Goserelin Acetate

Given SC

Intervention Type: DRUG

Leuprolide Acetate

Given IM

Intervention Type: DRUG

Prednisone

Given PO

Intervention Type: DRUG

Questionnaire Administration

Ancillary studies

Intervention Type: OTHER

Talazoparib

Given PO

Intervention Type: DRUG

Other Intervention Names

CB7630; Yonsa; Zytiga; Casodex; Cosudex; ICI 176,334; ICI 176334; FE200486; Firmagon; ZDX; Zoladex; A-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; Viadur; .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-Prednisone; BMN 673; BMN-673

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tanya Dorff

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

City of Hope Medical Center

Duarte, California, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Tanya Dorff

Role: primary

tdorff@coh.org

626-359-8111

Other Identifiers

NCI-2020-10199

Identifier Type: REGISTRY

Identifier Source: secondary_id

20476

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

20476

Identifier Type: -

Identifier Source: org_study_id