Carboplatin-Enhanced Therapy in BRCA-Mutated or Neuroendocrine-Differentiated Aggressive Metastatic Castration-Sensitive Prostate Cancer

NCT07591467 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: 2026-525359-10-00CSET number 2025 / 4163
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 5

Brief Summary

The current standard of patients with de novo metastatic hormone sensitive prostate cancer (mHSPC) is to offer androgen deprivation therapy (ADT) with androgen receptor pathway inhibitors (ARPI). In addition, upfront 6 cycles of docetaxel, if patient is eligible, and prostate radiotherapy for those with low-volume disease are recommended. BRCA mutations (BRCAm) and neuroendocrine differentiation (NED) confer a poor prognosis in mHSPC and the current standard of care for these patients remains suboptimal. While PARP inhibitors have shown efficacy in BRCAm castration-resistant prostate cancer, concerns exist about their toxicity and resistance when used earlier in the mHSPC setting. Carboplatin has demonstrated activity in BRCAm and neuroendocrine tumors but has not been extensively studied in mHSPC. The combination of carboplatin and docetaxel is expected to enhance treatment efficacy and delay progression.

Conditions

BRCA-Mutated; Prostate Cancer; Neuroendocrine-Differentiated Aggressive Metastatic Castration-Sensitive Prostate Cancer

Keywords

De novo mHSCPC, neuroendocrine differentiation, BRCA mutations (BRCAm)

Outcome Measures

Primary Outcomes (1)

• Radiographic progression-free survival

  To demonstrate that the addition of carboplatin to SoC therapies prolongs radiographic progression-free survival in patients with de novo mHSPC harboring a BRCA gene alteration and in patients with de novo mHSCPC showing neuroendocrine differentiation. Radiographic progression is defined according to the Prostate Cancer Working Group 4 (PCWG4) criteria.

  from randomization to radiographic progression or death, maximum 10 years

Study Arms (2)

Experimental arm

EXPERIMENTAL

Lifelong continuous ADT and darolutamide, similarly to standard of care, with the addition of docetaxel (60mg/m² per cycle) and carboplatin, with an area under the curve (AUC) of 4 mg/mL/min (AUC 4), 6 cycles + G-CSF support. For eligible patients, prostate radiotherapy, at least 3 weeks after the completion of chemotherapy.

Drug: Experimental

Control arm: Standard of care (SoC)

NO INTERVENTION

Standard of care therapies consisting of lifelong ADT and continuous darolutamide, docetaxel (75 mg/m² per cycle, 6 cycles + G-CSF support) and for eligible patients, prostate radiotherapy, at least 3 weeks after the completion of chemotherapy.

Interventions

Experimental DRUG

Lifelong continuous ADT and darolutamide, similarly to standard of care, with the addition of docetaxel (60mg/m² per cycle) and carboplatin, with an area under the curve (AUC) of 4 mg/mL/min (AUC 4), 6 cycles + G-CSF support. For eligible patients, prostate radiotherapy, at least 3 weeks after the completion of chemotherapy.

Experimental arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Gender Eligibility Details: Male aged ≥ 18 years old and ≤ 80 years old.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically proven adenocarcinoma of the prostate (any T stage, Gleason score or PSA level).
• De novo metastatic disease documented by a positive bone scan or CT scan or an MRI. For patients with nodal metastases only, only patients with extra-pelvic enlarged lymph nodes (lymph nodes located above the iliac bifurcation) can be included if they have either: at least one extra-pelvic lymph node ≥ 2 cm, or extra-pelvic lymph node(s)≥1 cm if the patients also have at least one pelvic lymph node ≥ 1.5 cm.
• Presence of pathogenic BRCA gene alteration (BRCAm cohort) OR histologically adenocarcinoma of the prostate with neuroendocrine differentiation (NED cohort)
• For the BRCAm cohort: confirmation of a pathogenic BRCA gene alteration by historical analysis, using one of the following:
• Circulating tumor DNA (ctDNA) analysis
• Tumor tissue analysis (archival sample permitted)
• Historical germline testing results
• For the NED cohort: histologically adenocarcinoma of the prostate with neuroendocrine differentiation41. NED is defined as either:
• Presence of mixed tumors with prostate adenocarcinoma associated with small cell or large cell neuroendocrine carcinoma according to WHO classification55 (5th edition). Pure small cell or large cell neuroendocrine carcinoma is not accepted (prostate adenocarcinoma component should express NKX3.1, AR and/or PSA to exclude pure small cell or large cell NE carcinoma)
• Or immunohistochemical staining showing some degree of neuroendocrine differentiation within adenocarcinoma (positivity of at least 2 of the following: chromogranin A, synaptophysin, TTF1 or INSM1). Threshold for NE markers positivity is ≥ 1% tumor cells. Co-expression of neuroendocrine markers with AR, NKX3.1 and/or PSA is allowed for these cases. If the patient has both a BRCA alteration and evidence of NED on his biopsy, he will be randomized in the BRCA cohort.
• Patients with ECOG PS ≤ 1, or patient with PS 2, provided PS alteration is disease-related.
• Life expectancy of at least 6 months.
• Male aged ≥ 18 years old and ≤ 80 years old.
• Hematology values: Hemoglobin ≥ 10.0 g/dL, Platelet count ≥ 100,000/mL, Neutrophil ≥ 1500 cells/mm³ (or neutrophil ≥ 1000 cells/mm³ in case of ethnic neutropenia).
• Biochemistry values: Renal function: Serum creatinine \< 1.5 x ULN or a calculated creatinine clearance ≥ 60 mL/min, Liver function: Serum bilirubin ≤ 1.5 x ULN (except for patients with documented Gilbert's disease), AST and ALT ≤ 1.5 x ULN (and ≤ 5 ULN in case of liver metastases), ALK-P ≤ 2.5 x ULN (in case of bone metastasis, ALK-P\<1000U/L if bilirubin is normal).

You may not qualify if:

• Patients with previous definitive local treatment directed to prostate primary cancer (radiotherapy, brachytherapy, radical prostatectomy, ultrasound, cryotherapy, or other). A previous trans-urethral resection of the prostate (TURP) and previous local treatments of metastases are allowed.
• Prior cytotoxic chemotherapy or biological therapy for the treatment of prostate cancer. Prior exposure to carboplatin or other platinum containing compounds.
• Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory neuropath\\\>= grade 2, per the Common Terminology Criteria for Adverse Events version 6.0.
• Patients known to be human immunodeficiency virus (HIV) positive, symptomatic viral hepatitis or chronic liver disease.
• Patient with administration of live or live attenuated vaccines (strongly discouraged in patients) and is formally contraindicated in the case of the yellow fever vaccine.
• Severe or moderate hepatic impairment (Child - Pugh class C or B).
• Clinically known significant heart disease in the past 6 months as evidenced by myocardial infarction, or arterial thrombotic events, severe or unstable angina, or New York Heart association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of \< 50% at baseline, atrial fibrillation, or other cardiac arrhythmia requiring therapy.
• History of malignancy, except non-melanoma skin cancer, with low risk of recurrence within 24 months.
• Known allergies, hypersensitivity or intolerance to carboplatin or other platinum containing compounds.
• Pathological finding consistent with pure small cell carcinoma of the prostate.
• Patients already included in another therapeutic trial involving an experimental drug (patient in a non-experimental trial with no modification of the patient's care can be included).
• Patients with significantly altered mental status prohibiting the understanding of the study or with psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule or any condition which, in the opinion of the investigator, would preclude participation in this trial.
• Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent.

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead
• PHRC, Ministry of Health France: collaborator

Study Sites (5)

Hôpital Saint André

Bordeaux, 33075, France

Location

CLCC-Léon Bérard

Lyon, 69008, France

Location

CLCC Paoli-Calmettes

Marseille, 13009, France

Location

CLCC-ICL

Nancy, 54519, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Central Study Contacts

Alice BERNARD-TESSIER, MD.

CONTACT

+ 33(0)1 42 11 64 44; ALICE.BERNARD-TESSIER@gustaveroussy.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: * Control arm: standard of care therapies consisting of lifelong ADT and continuous darolutamide, docetaxel (75 mg/m² per cycle, 6 cycles + G-CSF support) and for eligible patients, prostate radiotherapy, at least 3 weeks after the completion of chemotherapy. * Experimental arm: lifelong continuous ADT and darolutamide, similarly to standard of care, with the addition of docetaxel (60mg/m² per cycle) and carboplatin, with an area under the curve (AUC) of 4 mg/mL/min (AUC 4), 6 cycles + G-CSF support. For eligible patients, prostate radiotherapy, at least 3 weeks after the completion of chemotherapy.

Study Record Dates

• First Submitted: May 5, 2026
• First Posted: May 15, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2036
• Study Completion (Estimated): December 1, 2036
• Last Updated: May 15, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

FR (5)