Clinical trial NCT03652493: Trial Evaluating the Efficacy of CARBOPLATIN in Metastatic Prostate Cancer With Gene Alterations in the Homologous Recombination Pathway
Official title: Multicentre, Open-label Phase 2 Trial Evaluating the Efficacy of CARBOPLATIN in Metastatic Prostate Cancer With Gene Alterations in the Homologous Recombination Pathway
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Castration-resistant Prostate Cancer
Metastasis
Keywords: Anomaly of the Homologous Recombination (HR) pathway
Carboplatin
Lead sponsor: Centre Francois Baclesse
Sponsor class: OTHER
Collaborators: name: French Interregional Group of Clinical Research and Innovation
name: Ligue Contre le Cancer (French association Against Cancer)
First posted: 2018-08-29
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy of carboplatin on metastatic prostatic carcinoma resistant to castration Efficacy of carboplatin: The best radiological tumoral response rate
timeFrame: Up to 27 weeks (9 cycles)
measure: Efficacy of carboplatin: biological response rate defined by value of PSA
timeFrame: Up to 27 weeks (9 cycles)
Secondary outcomes:
Other outcomes:
Locations:
city: Caen
country: France
facility: Centre François Baclesse
city: Lille
country: France
facility: Centre Oscar Lambret
city: Rouen
country: France
facility: Chu Rouen
city: Villejuif
country: France
facility: Institut Gustave ROUSSy IGR
Study officials:
References: