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

NCT04734730 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 20476NCI-2020-10199P30CA033572
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Prostate specific antigen (PSA) nadir < 0.2

  Will be estimated with 95% Clopper-Pearson interval.

  At 12 months

Secondary Outcomes (5)

• Objective response rate

  Up to 2 years

• PSA responses

  Up to 2 years

• Radiographic progression-free survival (PFS)

  Up to 2 years

• Patient reported outcomes

  Up to 2 years

• Androgen receptor (AR) genetic variations

  Up to 2 years

Other Outcomes (1)

• Circulating tumor deoxyribonucleic acid (ctDNA)

  At baseline and 12 weeks

Study Arms (1)

Treatment (talazoparib, androgen deprivation therapy)

EXPERIMENTAL

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.

Drug: Abiraterone Acetate; Drug: Bicalutamide; Drug: Degarelix; Drug: Goserelin Acetate; Drug: Leuprolide Acetate; Drug: Prednisone; Other: Questionnaire Administration; Drug: Talazoparib

Interventions

Questionnaire Administration OTHER

Ancillary studies

Treatment (talazoparib, androgen deprivation therapy)

Talazoparib DRUG

Given PO

Also known as: BMN 673, BMN-673

Treatment (talazoparib, androgen deprivation therapy)

Abiraterone Acetate DRUG

Given PO

Also known as: CB7630, Yonsa, Zytiga

Treatment (talazoparib, androgen deprivation therapy)

Bicalutamide DRUG

Given PO

Also known as: Casodex, Cosudex, ICI 176,334, ICI 176334

Treatment (talazoparib, androgen deprivation therapy)

Degarelix DRUG

Given SC

Also known as: FE200486, Firmagon

Treatment (talazoparib, androgen deprivation therapy)

Goserelin Acetate DRUG

Given SC

Also known as: ZDX, Zoladex

Treatment (talazoparib, androgen deprivation therapy)

Leuprolide Acetate DRUG

Given IM

Also known as: 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

Treatment (talazoparib, androgen deprivation therapy)

Prednisone DRUG

Given PO

Also known as: .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

Treatment (talazoparib, androgen deprivation therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; bicalutamide; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; Goserelin; Leuprolide; luprolide acetate gel depot; Prednisone; deltacortene; prednylidene; talazoparib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Pregnadienediols; Pregnadienes; Pregnanes

Study Officials

• Tanya Dorff

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2021
• First Posted: February 2, 2021
• Study Start: May 4, 2021
• Primary Completion (Estimated): August 23, 2027
• Study Completion (Estimated): August 23, 2027
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

US (1)