Trial Evaluating the Efficacy of CARBOPLATIN in Metastatic Prostate Cancer With Gene Alterations in the Homologous Recombination Pathway

Study Overview
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Brief Summary
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The investigators propose a phase II study to evaluate the efficacy of carboplatin monotherapy in the tumor subgroup of metastatic castration-resistant prostatic carcinomas with somatic abnormality in the Homologous Recombination (HR) pathway. This study may also better characterize the molecular abnormalities of tumors required for the carboplatin response

Official Title
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Multicentre, Open-label Phase 2 Trial Evaluating the Efficacy of CARBOPLATIN in Metastatic Prostate Cancer With Gene Alterations in the Homologous Recombination Pathway

Conditions
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Castration-resistant Prostate Cancer, Metastasis

Intervention / Treatment
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* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients > 18 years old Patients with adenocarcinoma or poorly differentiated prostate carcinoma, histologically confirmed (small-cell histology or high-grade neuroendocrine histology excluded) Tumor presenting a somatic pathogenic variant likely to alter the homologous recombination pathway previously detected on a tumor biopsy or on circulating tumor DNA, or germinal mutation among the list of genes defined in the study Castration-resistant tumor defined by progression despite well-conducted androgen deprivation treatment: testosterone ≤50ng /dL agonist / antagonist of luteinizing hormone-releasing hormone (LHRH) or surgical castration. The patient must agree to continue concomitant LHRH-mediated (agonist or antagonist) therapy throughout the duration of the study regimen for patients with no history of surgical castration. Patients must have performed at least one line of chemotherapy by taxane in case of castration resistance: Patients who have received docetaxel treatment in a hormone-sensitive situation must have received at least treatment with cabazitaxel in case of castration resistance Patients who have not received chemotherapy in a hormone-sensitive situation must have received docetaxel AND cabazitaxel or have a contraindication to discontinue treatment. Patients must have been treated with at least 2nd generation hormone therapy (eg, abiraterone acetate or enzalutamide) Patients may have been treated with a poly (ADP-ribose) polymerase inhibitor (PARP) Performance Status <2 Metastatic disease progressive Exclusion Criteria: Absence of previous treatment with taxane in situation of sensitivity or resistance to castration. Absence of previous treatment with cabazitaxel in case of resistance to castration (except contraindication explaining the non-administration of treatment) No treatment with 2nd generation hormone therapy (eg abiraterone acetate or enzalutamide) unless contraindicated to explain non-administration of treatment Previous treatment with platinum Symptomatic and untreated central nervous system (CNS) metastases. Patients with asymptomatic and pre-treated CNS metastases are included if they are clinically stable (not requiring corticosteroid therapy for 28 days) and must have a brain MRI evaluation at screening and during follow-up.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CARBOPLATIN<br>CARBOPLATIN in Intraveinous Dose AUC 5 according to Calvert every 3 weeks, for a duration of 6 to 9 cycles | Drug: Carboplatin<br>* Tumoral evaluation every 3 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of carboplatin on metastatic prostatic carcinoma resistant to castration Efficacy of carboplatin: The best radiological tumoral response rate | Tumoral response rate (TR) defined according to the recommendations of the PCWG3 criteria : Objective radiological response | Up to 27 weeks (9 cycles) | 
| Efficacy of carboplatin: biological response rate defined by value of PSA | Biological response rate (TR) defined according to the recommendations of the PCWG3 criteria : Decrease of PSA ≥ 50%, | Up to 27 weeks (9 cycles) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anomaly of the Homologous Recombination (HR) pathway, Carboplatin