A Multicenter, Open Label, Randomized Phase II Trial to Evaluate the Efficacy of Talazoparib Plus Enzalutamide as First Line Treatment for Patients With Metastatic Castration Resistant Prostate Cancer Following Progression on Abiraterone

Status: Recruiting
Location: See all (12) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

The purpose of this clinical trial is to determine the anti-tumor activity of talazoparib plus enzalutamide as first line treatment for metastatic castration resistant prostate cancer (mCRPC) in participants whose disease has progressed on abiraterone. The main questions it aims to answer are: * Does talazoparib plus enzalutamide improve efficacy in metastatic castration resistant prostate cancer (mCRPC) compared to enzalutamide alone? * What is the time to disease progression \[radiographic, Prostate Specific Antigen (PSA), clinical\] in participants treated with talazoparib plus enzalutamide after progression on abiraterone? * What medical problems do participants have when receiving talazoparib plus enzalutamide? Researchers will compare the combination of talazoparib and enzalutamide as a first-line treatment for mCRPC to see if the combination improves the PSA response rate and delays progression compared to enzalutamide alone. The safety and tolerability of the combination (talazoparib and enzalutamide) will also be studied

Eligibility
Participation Requirements
Sex: Male
Minimum Age: 18
Healthy Volunteers: f
View:

• Male age 18 or older.

• Histological diagnosis of prostate adenocarcinoma without neuroendocrine differentiation or small cell features.

• Willing and able to provide written informed consent to participate in the study. Written consent must be given before registration, according to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) / Good clinical practice (GCP), and national/local regulations.

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Willing to provide tumor biopsies during the study. Note: At study entry, the pre-treatment fresh tumor biopsy could be replaced by an archived tumor biopsy upon agreement from the study chief investigator if such biopsy has been taken after progression to metastatic castration resistance and has both archived fresh-frozen material and a Formalin-fixed and paraffin-embedded (FFPE) block with a minimum tumor content more less than30 percent. Still the patient must be amenable and willing to undergo a new mandatory post-treatment biopsy.

• Willing to provide blood samples for biomarker analysis.

• Willing to give consent to sequencing of DNA damage repair (DDR) genes for analysis of the prevalence of somatic and germline aberrations in DNA damage repair genes.

• Metastatic (M1) prostate cancer documented by bone scan, or soft tissue disease documented by computed tomography (CT), or magnetic resonance imaging (MRI).

• Asymptomatic or minimally symptomatic prostate cancer at screening.

⁃ Estimated life expectancy of greater than or equal to 6 months from screening.

⁃ Ongoing androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) agonist or antagonist for participants who have not undergone bilateral orchiectomy must be in place before screening and must continue throughout the study.

⁃ Disease progression after at least 12 weeks of treatment with abiraterone for metastatic hormone-sensitive prostate cancer. Progression is defined as:

‣ a. PSA rise of greater than or equal to 25 percent and an absolute increase of greater than or equal to 2 ng/mL above nadir (or baseline for participants with no PSA decline), confirmed by a second PSA value at least 3 weeks later.

‣ and / or b. Limited radiographic progression: maximum of 2 new bone metastases, no new soft tissue metastasis and less than50percentincrease in the size of measurable soft tissue lesions.

‣ 13\. Participants who have received prior docetaxel must meet the following criteria:

‣ a. Received a maximum of 6 cycles of docetaxel for mHSPC. b. Received the last dose of docetaxel higher than 6 months prior to randomization.

‣ 14\. Adequate organ function within 28 days before the first study treatment on Day 1, defined by the following:

• Haemoglobin greater than or equal to 10 g/dL, no blood transfusions within 14 days before obtaining the haematology laboratory tests at screening,

• Platelets greater than or equal to 100,000/μL no platelets transfusions within 14 days before obtaining the haematology laboratory tests at screening,

• Neutrophils greater than or equal to 1500/μL, no growth factors given within 14 days before obtaining the haematology laboratory tests at screening,

• Serum creatinine less than1.5X ULN or calculated creatinine clearance greater than or equal to 50 mL/min

• Albumin greater than 3 g/dL,

• AST or ALT less than 2.5 × ULN (less than 5 × ULN if liver function abnormalities are due to hepatic metastasis).

• Total serum bilirubin less than 1.5 × ULN (less than 3 × ULN for participants with documented Gilbert syndrome or for whom indirect bilirubin concentrations suggest an extrahepatic source of elevation).

• 15\. Ability to swallow study medication tablets and comply with study requirements.

• 16\. Agrees to use a condom and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant, starting contraception at screening and continue throughout the study period and for 3 months after the final treatment administration, unless the patient is unable to maintain intercourse due to the androgen deprivation.

• 17\. Subjects must not donate sperm starting at screening and throughout the study period and for 3 months after the final abiraterone acetate administration.

• 18\. Subject agrees not to participate in another interventional study while on treatment.

• 19\. Willing and able to comply with all scheduled visits, treatment plan, laboratory tests and other study procedures.

Locations
Other Locations
Spain
Institut Català d'Oncologia (ICO)
RECRUITING
Badalona
Hospital Universitario Cruces
RECRUITING
Barakaldo
Hospital Clínico y Provincial de Barcelona
RECRUITING
Barcelona
Hospital Universitario Del Mar.
RECRUITING
Barcelona
Hospital Universitario de Jerez de la Frontera
RECRUITING
Cadiz
Hospital 12 de Octubre
RECRUITING
Madrid
Hospital Clínico San Carlos
RECRUITING
Madrid
Hospital Universitario La Paz
RECRUITING
Madrid
Hospital Universitario Virgen de la Victoria
RECRUITING
Málaga
Consorcio Corporación Sanitaria Parc Taulí
RECRUITING
Sabadell
Hospital Universitario Marqués de Valdecilla
RECRUITING
Santander
Hospital Universitario Miguel Servet
RECRUITING
Zaragoza
Contact Information
Primary
Luis Gonzaga Paz-Ares Rodríguez
info@oncosur.org
+34 91 560 82 27
Backup
Elena Castro, Dra.
ecastro.imas12@h12o.es
627213615
Time Frame
Start Date: 2024-07-05
Estimated Completion Date: 2027-10-31
Participants
Target number of participants: 78
Treatments
Active_comparator: Control
Enzalutamide 160 mg orally daily continuously in 28-day cycles.
Experimental: Enzalutamide and Talazoparib
Enzalutamide 160 mg and Talazoparib 0.5 mg both orally daily and continuously in 28-day cycles.
Related Therapeutic Areas
Sponsors
Leads: Fundacion Oncosur

This content was sourced from clinicaltrials.gov

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