Progression under Olaparib: a randomized phaSE II trIal with docetaxel or carboplatin-docetaxel DOublet in mCRPC patieNts

Trial details

Who runs it

Azienda Provinciale Per I Servizi Sanitari

Trial code

EU 2023-503676-25-01

Record updated

2024. november 18.

Original description

To demonstrate the superiority of the combination of docetaxel + prednisone / carboplatin (Arm A) compared to docetaxel + prednisone (Arm B) in patients with mCRPC progressing after one androgen-receptor signaling inhibitor (ARSI) followed by olaparib.Read full original descriptionShow less

To demonstrate the superiority of the combination of docetaxel + prednisone / carboplatin (Arm A) compared to docetaxel + prednisone (Arm B) in patients with mCRPC progressing after one androgen-receptor signaling inhibitor (ARSI) followed by olaparib.

Inclusion: Histologically- or cytologically-confirmed prostate adenocarcinoma; Performance status ECOG <2; Ability to fill the quality of life questionnaire; Written informed consent; Metastatic Castration Resistant Prostate Cancer (mCRPC); Previous detection of BRCA mutation; Treatment for mCRPC with an ARSI and subsequent treatment with olaparib; Progressive disease while receiving Olaparib documented by: I. Increase in measurable disease (RECIST 1.1), and/or II. Appearance of new lesions, including those on bone scan (≥2 new lesions on 2 consecutive bone scans if progression disease diagnosed on bone scan only) consistent with progressive prostate cancer, and/or III. Rising PSA defined as 2 sequential increases above a previous lowest reference value. Each value must be obtained at least 1 week apart. A PSA value of at least 2 ng/ml is required at study entry. For patients evaluated with PET the progressive disease should be documented by at least one of the following criteria: I. appearance of at least two new lesions, and/or II. Increase of ≥30% of the uptake or of the tumoral volume; Effective castration (serum testosterone levels ≤0.50 ng/dL) by orchiectomy and/or LHRH agonists or antagonist with or without anti-androgens; Age ≥18 years.

Exclusion: Prior chemotherapy for prostate cancer; Prior isotope therapy, whole pelvic radiotherapy, or radiotherapy to >30% of bone marrow; Contraindications to the use of corticosteroid treatment; Any of the following within 3 months prior to randomization: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event; Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to randomization; Any other condition which in the judgment of the investigator would place the subject at undue risk or interfere with the study; History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease; Inadequate organ and bone marrow function as evidenced by: a. Hemoglobin <10.0 g/dL b. Absolute neutrophil count <1.5 x 109/L, c. Platelet count <100 x 109/L, d. AST and/or ALT >1.5 x ULN; e. Total bilirubin >1.5 x ULN, f. Serum Creatinine >1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated either according to Cockcroft-Gault formula. Creatinine clearance <60 mL/min will exclude the patient; Clinically significant cardiovascular disease including the following: a. Myocardial infarction within 6 months before screening; b. Uncontrolled angina within 3 months before screening; c. Congestive heart failure New York Heart Association class 3 or 4, or a history of congestive heart failure New York Heart Association class 3 or 4, unless a screening echocardiogram or multigated acquisition scan performed within 3 months before randomization demonstrates a left ventricular ejection fraction ≥ 50%; d. History of clinically significant ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes); e. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place; f. Hypotension as indicated by systolic blood pressure < 86 millimeters of mercury (mm Hg) at screening; g. Bradycardia as indicated by a heart rate of < 45 beats per minute on the screening electrocardiogram (ECG) and on physical examination; h. Uncontrolled hypertension as indicated by systolic blood pressure > 170 mm Hg or diastolic blood pressure > 105 mm Hg at screening; Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial (pTis, pTa, and pT1) bladder cancer are allowed, as well as any other cancer for which chemotherapy has been completed >5 years ago and from which the patient has been disease-free for >5 years; Inability to ensure follow-up.

EU CTIS 2023-503676-25-01