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

Recruiting now · Phase 2

Conditions studied: Metastatic Prostate Cancer

In brief

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

Key facts

Study ID: NCT06582628
Run by: Fundacion Oncosur
People needed: 78
Starts: 2024-07-05
Expected to finish: 2027-10-31
Last updated by the study team: 2024-12-02

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: not accepted.

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.
12 .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:
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.
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).
Ability to swallow study medication tablets and comply with study requirements.

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
Documented congestive heart failure (New York Heart Association Class, NYHA functional classification III-IV)
Uncontrolled, persistent hypertension defined as systolic blood pressure less than 170mmHg or diastolic blood pressure less than100mmHg. Subjects with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
Participants with any of the following cardiac conduction abnormalities: Ventricular arrhythmias except for benign premature ventricular contractions
Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication.
Conduction abnormality requiring a pacemaker.
Other cardiac arrhythmia not controlled with medication.
Any clinically significant gastrointestinal disorder affecting absorption (i.e., extensive small bowel resection, active inflammatory bowel disease).
Active or symptomatic viral hepatitis or chronic liver disease.
Known/possible hypersensitivity, allergies to enzalutamide, talazoparib or any of capsule excipients.
Other malignancy except:

Where it is running

Institut Català d'Oncologia (ICO) — Badalona, Barcelona, Spain (enrolling)
Consorcio Corporación Sanitaria Parc Taulí — Sabadell, Barcelona, Spain (enrolling)
Hospital Universitario Marqués de Valdecilla — Santander, Cantabria, Spain (enrolling)
Hospital Universitario de Jerez de la Frontera — Cadiz, Cádiz, Spain (enrolling)
Hospital Universitario Cruces — Barakaldo, Vizcaya, Spain (enrolling)
Hospital Universitario Del Mar. — Barcelona, Spain (enrolling)
Hospital Clínico y Provincial de Barcelona — Barcelona, Spain (enrolling)
Hospital Clínico San Carlos — Madrid, Spain (enrolling)
Hospital 12 de Octubre — Madrid, Spain (enrolling)
Hospital Universitario La Paz — Madrid, Spain (enrolling)
Hospital Universitario Virgen de la Victoria — Málaga, Spain (enrolling)
Hospital Universitario Miguel Servet — Zaragoza, Spain (enrolling)

Full record on ClinicalTrials.gov

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