A Study of Talazoparib With or Without Enzalutamide in People With Prostate Cancer Who Have Previously Received Abiraterone or Darolutamide (TALENT)

About the Study

The purpose of this study is to find out whether talazoparib in combination with enzalutamide or talazoparib alone delays cancer progression in people with metastatic castration-resistant prostate cancer (mCRPC) who have certain changes in their tumor known as homologous recombination repair (HRR) mutations and have previously received and progressed on either abiraterone acetate or darolutamide. HRR mutations can affect how well your body fixes breaks that can happen in your DNA. Talazoparib is a type of targeted therapy known as a PARP inhibitor. Enzalutamide is a type of hormone therapy known as an androgen receptor inhibitor. Interested patients should contact a participating location to be evaluated for study participation and may be able to continue to receive care locally throughout the duration of the study.

What the Study Involves

This is a randomized study, which means participants will be assigned by chance (like the flip of a coin) to one of two treatment groups. People in the study will receive either talazoparib with enzalutamide or talazoparib alone. Both treatments are pills taken by mouth every day. Participants will continue treatment until their cancer gets worse, side effects become too difficult, or their doctor decides the treatment is no longer helping.

If you join this study, you will be asked to:

• Review and sign a consent form before any study tests or procedures are done.
• Complete screening tests to make sure the study is a good fit for you. These may include a physical exam, vital signs, blood tests, an electrocardiogram (ECG) to check your heart, imaging scans and questionnaires about how you are feeling.
• Be assigned by chance to take either talazoparib plus enzalutamide or talazoparib alone.
• Take your assigned study medicine by mouth every day.
• Have study visits every month for the first 7 months, then every 3 months after that. Some visits may be in person and some may be done by telehealth.
• Have regular checkups during treatment, including physical exams, vital signs, blood tests and imaging scans. Imaging is done every 2 months for the first 7 months, then every 3 months after that.
• Complete questionnaires about symptoms and quality of life on the same schedule as imaging scans.
• Have 3 follow-up visits after stopping treatment: one about 7 days after the last dose, one about 6 months later and one about 12 months later.

Lead Researchers/Study PIs and Affiliation

Alicia Morgans, MD
Dana Farber Cancer Institute
857-215-1605
[email protected]
 

Karen Autio, MD
Memorial Sloan Kettering Cancer Center
646-422-4632
[email protected]

Eligibility:

• Metastatic castration-resistant prostate cancer that can be seen on imaging.
• Presence of an HRR mutation in at least one of the following genes: BRCA1, BRCA2, ATM, CDK12, CHEK2, PALB2, MLH1, NBN, ATR, FANCA, MRE11A, RAD51C found on tumor testing.
• Previous disease progression while receiving either abiraterone acetate with prednisone or darolutamide.

Exclusions:

• Prior treatment with a PARP inhibitor.
• Prior platinum-based chemotherapy for the treatment of prostate cancer.
• Any other active cancer at time of first dose of study treatment or diagnosis of another cancer within the last 2 years that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer or superficial bladder cancer.
• History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma). Also, history of loss of consciousness or mini-stroke within the last 12 months.
• Medical conditions such as uncontrolled high blood pressure, diabetes, or heart disease.