Talazoparib Plus Enzalutamide After Progression to Abiraterone in Metastatic Prostate Cancer: (TEAM PC)

NCT06582628 | Recruiting Phase 2 DMC

• 2 other identifiers: TEAM PC_FOS06/20232023-510536-37-00
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 12

Brief 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

Conditions

Metastatic Prostate Cancer

Keywords

Prostatic Diseases; Prostatic Cancer; metastatic castration resistant prostate cancer (mCRPC); prostate adenocarcinoma; metastatic hormone-sensitive prostate cancer; Poly (ADP-ribose) Polymerases (PARP); Prostate Specific Antigen; Abiraterone

Outcome Measures

Primary Outcomes (2)

• PSA response (PSA50)

  Percentage of participants with a PSA decline greater than or equal to 50 percent from baseline confirmed by a consecutive PSA value (taken at least 3 weeks apart), prior to PSA progression

  within the first 16 weeks

• Objective response rate (ORR)

  Defined as the best overall radiographic response (partial or complete) during the first 16 weeks on follow up as per investigator assessment of soft tissue/visceral disease per RECIST 1.1 in subjects who have a measurable tumour and/or Prostate Cancer Working Group 3 (PCWG3) criteria for bone metastases

  during the first 16 weeks

Secondary Outcomes (7)

• Radiographic Progression Free Survival (rPFS)

  Through study completion, an average of 2 years

• Time to PSA Progression (TTPP)

  Through study completion, an average of 2 years

• Time to unequivocal clinical progression (TTCP)

  Through study completion, an average of 2 years

• Progression Free Survival (PFS)

  Through study completion, an average of 2 years

• Incidence of adverse events (AEs)

  Through study completion, an average of 2 years

Other Outcomes (19)

• Assessment of PSA response rate

  Through study completion, an average of 2 years

• Assessment of ORR

  Through study completion, an average of 2 years

• Assessment of rPFS

  Through study completion, an average of 2 years

Study Arms (2)

Control

ACTIVE COMPARATOR

Enzalutamide 160 mg orally daily continuously in 28-day cycles.

Drug: Enzalutamide capsule

Enzalutamide and Talazoparib

EXPERIMENTAL

Enzalutamide 160 mg and Talazoparib 0.5 mg both orally daily and continuously in 28-day cycles.

Drug: Enzalutamide capsule and Talazoparib capsule

Interventions

Enzalutamide capsule DRUG

Enzalutamide capsules 160 mg orally daily

Control

Enzalutamide capsule and Talazoparib capsule DRUG

Enzalutamide capsules 160 mg plus talazoparib capsules 0.5 mg, both orally daily

Enzalutamide and Talazoparib

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Prior abiraterone treatment for less than 12 weeks or disease progression (either PSA or radiographic progression) within 6 months of starting abiraterone.
• Disease progression less than 6 months after the last administration of docetaxel for mHSPC.
• Known or suspected brain metastasis or active leptomeningeal disease.
• A finding of superscan in a bone scan at screening. Superscan is defined as a bone scan which demonstrates markedly increased skeletal radioisotope uptake relative to soft tissues in association with absent or faint renal activity (absent kidney sign).
• Symptomatic or impending spinal cord compression or cauda equina syndrome.
• Use of opiate analgesia for pain from prostate cancer with average Brief pain inventory (BPI) questionnaire score higher than 6 and/or uncontrolled prostate cancer-related pain requiring increasing doses of opiates within 4 weeks prior to randomization
• Prior treatment with an AR-targeted therapy (enzalutamide, apalutamide, darolutamide, ketoconazole) other than abiraterone for mHSPC; chemotherapy other than 6 cycles of docetaxel for mHSPC, immunotherapy or radiopharmaceuticals.
• Therapeutic radiation therapy within, 14 days (7 days for limited-field palliative radiotherapy) prior to study enrolment, or participants who have not recovered from radiotherapy-related toxicities to grade less than or equal to 1 according to NCI-CTCAE v.5.0.
• Major surgery within 4 weeks prior to randomization or participants who have not recovered from the side effects of any major surgery.
• Administration of an investigational therapeutic or invasive surgical procedure (not including surgical castration) within 30 days of Cycle 1 Day 1 or currently enrolled in an investigational study.
• History of seizure or any condition that may predispose to seizure (i.e., prior significant brain trauma, brain vascular malformation, etc) or subjects that have had an unexplained loss of consciousness or transient ischemic attacks within 1 year previous to scheduled day 1 of treatment.
• Congenital long QT syndrome or ECG at screening with QT interval corrected using Fridericia's formula (QTcF) greater than 500 milliseconds.
• articipants with clinically significant cardiovascular disease including but not limited to any of the following:
• Stroke, transient ischemic attack, unstable angina pectoris or documented myocardial infarction within 12 months prior to study entry.
• Symptomatic pericarditis or clinically significant pericardial effusion or myocarditis

Sponsors & Collaborators

• Fundacion Oncosur: lead

Study Sites (12)

Institut Català d'Oncologia (ICO)

Badalona, Barcelona, 08916, Spain

RECRUITING

Consorcio Corporación Sanitaria Parc Taulí

Sabadell, Barcelona, 08208, Spain

RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

RECRUITING

Hospital Universitario de Jerez de la Frontera

Cadiz, Cádiz, 11407, Spain

RECRUITING

Hospital Universitario Cruces

Barakaldo, Vizcaya, 48903, Spain

RECRUITING

Hospital Universitario Del Mar.

Barcelona, 08003, Spain

RECRUITING

Hospital Clínico y Provincial de Barcelona

Barcelona, 08036, Spain

RECRUITING

Hospital Clínico San Carlos

Madrid, 28040, Spain

RECRUITING

Hospital 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, 50009,, Spain

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms; Prostatic Diseases

Interventions

enzalutamide; talazoparib

Condition Hierarchy (Ancestors)

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

Study Officials

• Elena Castro, Dra.

  Hospital 12 de Octubre

  PRINCIPAL INVESTIGATOR

• Maria Ruiz Vico, Dra.

  Hospital 12 de Octubre

  STUDY CHAIR

• David Olmos, Dr.

  Hospital 12 de Octubre

  STUDY CHAIR

Central Study Contacts

Luis Gonzaga Paz-Ares Rodríguez

CONTACT

+34 91 560 82 27; info@oncosur.org

Elena Castro, Dra.

CONTACT

627213615; ecastro.imas12@h12o.es

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Exceptionally the Cross-over model will be allowed: from the control arm to the experimental arm upon progression is allowed in participants who meet certain criteria.

Study Record Dates

• First Submitted: August 30, 2024
• First Posted: September 3, 2024
• Study Start: July 5, 2024
• Primary Completion: January 31, 2026
• Study Completion (Estimated): October 31, 2027
• Last Updated: December 2, 2024

Record last verified: 2024-11

Locations

ES (12)