This study focuses on men with metastatic castration-sensitive prostate cancer who have specific genetic mutations in their DNA repair genes. The research examines the effectiveness of combining two medications: talazoparib and enzalutamide. Metastatic means the cancer has spread from the prostate to other parts of the body, while castration-sensitive means the cancer still responds to treatments that lower testosterone levels.
The purpose of this study is to determine if adding talazoparib to enzalutamide treatment works better than using enzalutamide with a placebo in treating this type of prostate cancer. The study uses DNA repair gene mutations testing to identify suitable participants. During the study, participants will receive either the combination of talazoparib and enzalutamide or enzalutamide with a placebo.
Throughout the treatment period, which may last up to 24 months, participants will continue to receive hormone therapy that reduces testosterone levels. The study will monitor how the cancer responds to treatment through regular medical examinations and imaging tests. These tests will help determine if the cancer is stable, improving, or getting worse.
1Initial medication assignment
You will be randomly assigned to one of two treatment groups:
You must continue taking your prescribed hormone therapy (ADT) throughout the entire study
This involves regular injections of medication that lowers testosterone levels, unless you have had previous surgery to remove both testicles
3Regular health monitoring
Your cancer progression will be monitored through regular imaging scans
Doctors will check for changes in both soft tissue using CT or MRI scans
Bone scans will be performed to check for bone-related changes
4Physical condition assessment
Your overall physical condition will be regularly evaluated using the ECOG scale
This scale measures your ability to perform daily activities and self-care
5Study duration
The study continues until August 2027
Your participation may end earlier if your condition changes or as determined by your doctor
Who Can Join the Study?
Must have confirmed prostate cancer (specifically adenocarcinoma type) that has been verified through tissue examination
Must undergo testing to confirm specific genetic mutations (called DDR gene mutations) through blood sample or tissue analysis
Must be receiving ongoing hormone therapy (ADT) with specific medications, or have had surgical removal of testicles (bilateral orchiectomy). The hormone therapy must continue throughout the study
Must have cancer that has spread (metastatic disease) confirmed by:
Bone scan showing spread to bones, or
CT or MRI scan showing spread to soft tissues
Must have good physical functioning ability, scoring either 0 (fully active) or 1 (restricted in physically strenuous activity) on the ECOG performance scale
Must be male
Must be an adult (18 years or older)
Cannot have cancer spread limited to only pelvic lymph nodes
Cannot have a condition called superscan (a specific type of bone scan result)
Who Cannot Join the Study?
Prior treatment with PARP inhibitors (medications that block DNA repair in cancer cells)
Known active brain or spinal cord metastases (cancer that has spread to brain or spine)
Significant heart conditions, including:
Heart attack within past 6 months
Uncontrolled high blood pressure
Unstable heart rhythm problems
Severe liver problems or active liver disease
Other active cancers requiring treatment (except non-melanoma skin cancer)
History of seizures or conditions that may cause seizures
Major surgery within 4 weeks before starting the study
Any serious medical condition that could interfere with study participation
Unable to swallow oral medications
Known allergic reactions to the study medications
Participation in other clinical trials within 4 weeks before this study
Female patients (study is only for male participants)
Talazoparib is a medication that belongs to a class of drugs called PARP inhibitors. It works by blocking an enzyme that helps repair damaged DNA in cancer cells, which can help stop cancer cells from growing and dividing. In this trial, it is being studied for treating prostate cancer that has specific genetic mutations.
Enzalutamide is a hormone therapy medication used to treat prostate cancer. It works by blocking the effects of testosterone and other male hormones that can stimulate prostate cancer growth. This medication helps to slow down or stop the growth of prostate cancer cells.
Metastatic Castration-sensitive Prostate Cancer – A condition where prostate cancer has spread beyond the prostate gland to other parts of the body, but still responds to treatments that lower testosterone levels. In this type of cancer, the tumor cells continue to be dependent on male hormones (androgens) for their growth. The cancer typically spreads to lymph nodes, bones, or other organs while maintaining its sensitivity to hormone therapy. This form of prostate cancer represents a stage where the disease has become metastatic but remains responsive to treatments that reduce testosterone levels in the body.
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