TALAZOPARIB for Metastatic castration-resistant prostate cancer | Prostate adenocarcinoma

Inclusion criteria

• {"criterion_text":"- Male age 18 or older"}
• {"criterion_text":"- Estimated life expectancy of ≥ 6 months from screening"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Disease progression after at least 12 weeks of treatment with abiraterone for metastatic hormone-sensitive prostate cancer. Progression is defined as: a.\tPSA rise of ≥ 25% and an absolute increase of ≥ 2 ng/mL above nadir (or baseline for patients with no PSA decline), confirmed by a second PSA value at least 3 weeks later. and / or b.\tLimited radiographic progression: maximum of 2 new bone metastases, no new soft tissue metastasis and <50% increase in the size of measurable soft tissue lesions."}
• {"criterion_text":"- Participants who have received prior docetaxel must meet the following criteria: a.\tReceived a maximum of 6 cycles of docetaxel for mHSPC. b.\tReceived the last dose of docetaxel ≥ 6 months prior to randomization."}
• {"criterion_text":"- Adequate organ function within 28 days before the first study treatment on Day 1 a. Haemoglobin ≥10 g/dL, no blood transfusions within 14 days before obtaining the haematology laboratory tests at screening, b. Platelets ≥100,000/μL no platelets transfusions within 14 days before obtaining the haematology laboratory tests at screening, c. Neutrophils ≥1500/μL, no growth factors given within 14 days before obtaining the haematology laboratory tests at screening, d. Serum creatinine <1.5X ULN or calculated creatinine clearance ≥ 50 mL/min e. Albumin > 3 g/dL, f. AST or ALT <2.5 × ULN (<5 × ULN if liver function abnormalities are due to hepatic metastasis). g. Total serum bilirubin <1.5 × ULN (<3 × ULN for participants with documented Gilbert syndrome or for whom indirect bilirubin concentrations suggest an extrahepatic source of elevation)."}
• {"criterion_text":"- Ability to swallow study medication tablets and comply with study requirements"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Subjects must not donate sperm starting at screening and throughout the study period and for 3 months after the final abiraterone acetate administration"}
• {"criterion_text":"- Subject agrees not to participate in another interventional study while on treatment."}
• {"criterion_text":"- Willing and able to comply with all scheduled visits, treatment plan, laboratory tests and other study procedures"}
• {"criterion_text":"- Histological diagnosis of prostate adenocarcinoma without neuroendocrine differentiation or small cell features"}
• {"criterion_text":"- Willing and able to provide written informed consent to participate in the study. Written consent must be given before registration, according to ICH/GCP, and national/local regulations"}
• {"criterion_text":"- ECOG performance status 0 or 1"}
• {"criterion_text":"- Willing to provide tumor biopsies during the study."}
• {"criterion_text":"- Willing to provide blood samples for biomarker analysis"}
• {"criterion_text":"- Willing to give consent to sequencing of DDR genes for analysis of the prevalence of somatic and germline aberrations in DNA damage repair genes"}
• {"criterion_text":"- Metastatic (M1) prostate cancer documented by bone scan, or soft tissue disease documented by computed tomography (CT), or magnetic resonance imaging (MRI)."}
• {"criterion_text":"- Asymptomatic or minimally symptomatic prostate cancer at screening."}

Exclusion criteria

• {"criterion_text":"- Prior abiraterone treatment for < 12 weeks or disease progression (either PSA or radiographic progression) within 6 months of starting abiraterone"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Congenital long QT syndrome or ECG at screening with QT interval corrected using Fridericia’s formula (QTcF)>500 milliseconds"}
• {"criterion_text":"- Patients with clinically significant cardiovascular disease including but not limited to any of the following: a)\tStroke, transient ischemic attack, unstable angina pectoris or documented myocardial infarction within 12 months prior to study entry. b)\tSymptomatic pericarditis or clinically significant pericardial effusion or myocarditis c)\tDocumented congestive heart failure (NYHA functional classification III-IV) d)\tUncontrolled, persistent hypertension defined as systolic blood pressure >170mmHg or diastolic blood pressure >100mmHg. Subjects with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment"}
• {"criterion_text":"- Patients with any of the following cardiac conduction abnormalities: a)\tVentricular arrhythmias except for benign premature ventricular contractions b)\tSupraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication. c)\tConduction abnormality requiring a pacemaker. d)\tOther cardiac arrhythmia not controlled with medication."}
• {"criterion_text":"- Any clinically significant gastrointestinal disorder affecting absorption (i.e., extensive small bowel resection, active inflammatory bowel disease)."}
• {"criterion_text":"- Active or symptomatic viral hepatitis or chronic liver disease,"}
• {"criterion_text":"- Known/possible hypersensitivity, allergies to enzalutamide, talazoparib or any of capsule excipients."}
• {"criterion_text":"- Other malignancy except: a)\tCarcinoma in situ or non-melanoma skin cancer. b)\tA cancer diagnosed and treated ≥ 5 years before randomization with no subsequent evidence of recurrence."}
• {"criterion_text":"- Any condition or situation which, in the opinion of the investigator, would put the subject at risk, may confound study results, or interfere with the subject’s participation in this study"}
• {"criterion_text":"- Disease progression < 6 months after the last administration of docetaxel for mHSPC"}
• {"criterion_text":"- Known or suspected brain metastasis or active leptomeningeal disease"}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Symptomatic or impending spinal cord compression or cauda equina syndrome"}
• {"criterion_text":"- Use of opiate analgesia for pain from prostate cancer with average BPI score ≥ 6 and/or uncontrolled prostate cancer-related pain requiring increasing doses of opiates within 4 weeks prior to randomization"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Therapeutic radiation therapy within, 14 days (7 days for limited-field palliative radiotherapy) prior to study enrolment, or patients who have not recovered from radiotherapy-related toxicities to grade ≤ 1 according to NCI-CTCAE v.5.0"}
• {"criterion_text":"- Major surgery within 4 weeks prior to randomization or patients who have not recovered from the side effects of any major surgery"}

Primary endpoints

• {"endpoint_text":"- PSA response: percentage of patients with PSA decline ≥ 50% from baseline PSA value at 12-16 weeks and/or","definition_or_measurement_approach":"PSA decline ≥ 50% from baseline PSA value measured at 12-16 weeks; percentage of patients meeting this threshold."}
• {"endpoint_text":"- Objective response rate: percentage of patients with 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 with measurable lesions.","definition_or_measurement_approach":"Investigator-assessed radiographic response (partial or complete) per RECIST 1.1 in subjects with measurable soft tissue/visceral lesions during the first 16 weeks; reported as percentage of patients with objective response."}

Secondary endpoints

• {"endpoint_text":"- Radiographic progression free survival (rPFS), based on RECIST v1.1 and/or PCGW3 guidelines","definition_or_measurement_approach":"Time from randomization to radiographic progression per RECIST v1.1 and/or PCWG3 criteria or death; assessed per imaging guidelines stated."}
• {"endpoint_text":"- Time to PSA progression (TTPP), based on PCGW3 guidelines.","definition_or_measurement_approach":"Time from randomization to PSA progression defined according to PCWG3 guidelines."}
• {"endpoint_text":"- Time to unequivocal clinical progression (TTCP), based on PCGW3 guidelines","definition_or_measurement_approach":"Time from randomization to unequivocal clinical progression per PCWG3 guidance."}
• {"endpoint_text":"- Incidence of adverse events (AEs), based on CTCAE v.5.0 criteria","definition_or_measurement_approach":"Incidence and severity of adverse events graded according to NCI CTCAE version 5.0."}

Spain

Earliest CTIS Part Ii Submission Date

03-05-2024

Latest Decision Or Authorization Date

05-06-2024

Processing Time Days

33

Number Of Sites

12

Number Of Participants

78

France

Earliest CTIS Part Ii Submission Date

10-07-2025

Latest Decision Or Authorization Date

05-09-2025

Processing Time Days

57

Number Of Sites

5

Number Of Participants

25

Primary sponsor

Full Name

Fundacion Oncosur

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain

Contract research organisations

Name

Start From Scracth S.L.

Responsibilities

sponsorDuties codes: 1, 12, 5, 8

Third parties

• {"country":"Spain","full_name":"Distefar Del Sur S.L.","duties_or_roles":"sponsorDuties codes: 14, 15 (code 15 value: Storage, supply, custody- medicinal product)","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Start From Scracth S.L.","duties_or_roles":"sponsorDuties codes: 1, 12, 5, 8","organisation_type":"Industry"}