Combining darolutamide with radiation therapy for advanced prostate cancer

Combination of Darolutamide and Stereotactic Body Radiation Therapy in Patients With Castration Resistant Prostate Cancer and Oligometastases on Functional Imaging

This study is testing if adding radiation therapy to a new hormone treatment can help men with advanced prostate cancer live longer and feel better.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 336 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Unicancer (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 4 sites (Lorient and 3 other locations)
• Trial ID: NCT06276465 on ClinicalTrials.gov

What this trial studies

This phase III trial evaluates the effectiveness of darolutamide, a new generation hormonal therapy, combined with stereotactic body radiation therapy (SBRT) for patients with oligometastatic castration-resistant prostate cancer (CRPC). Participants will be randomly assigned to receive either darolutamide alone or darolutamide with SBRT, alongside continuous androgen deprivation therapy. The study aims to determine if this combination can improve survival outcomes for patients whose cancer has spread but remains limited in number. Patients will be monitored for up to 60 months to assess treatment efficacy and safety.

Who should consider this trial

Good fit: Ideal candidates include adult males aged 18 and older with histologically confirmed adenocarcinoma prostate cancer who have experienced progression despite hormone therapy.

Not a fit: Patients with small cell or pure endocrine features of prostate cancer or those without a history of local treatment for localized prostate cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly prolong survival for patients with oligometastatic CRPC.

How similar studies have performed: Other studies have shown promising results with similar approaches, indicating potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

1. Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
2. Patients aged ≥18 years.
3. Patient with histologically confirmed of adenocarcinoma prostate cancer without small cell or pure endocrine features.
4. Patient with a history of local treatment with curative intent for localised prostate cancer, including surgery or radiotherapy.
5. Patients with castration resistant prostate cancer, defined as either:

   * An increasing PSA level, confirmed in 3 consecutive assessments performed at least 1 week apart. This despite androgen deprivation therapy and castrate levels of testosterone.
   * Tumour progression of soft tissue according to the response criteria in solid tumours (RECIST) version (v)1.1.
   * Tumour progression on bone scan, according to PCWG3 criteria.

   N.B. The two latter conditions only apply to the M1CRPC population.
6. Detection of 1 to 5 metastatic sites (pelvic lymph nodes included) on new generation PET using either choline, fluciclovine, or PSMA as tracer.
7. All metastatic sites must be amenable to stereotactic radiation therapy.
8. Patient with normal haematological function: absolute neutrophil count (ANC) \>1.0 x 10⁹/L, platelets count ≥100 x 10⁹/L, and haemoglobin ≥9.0 g/dL.
9. Patient with normal liver function with total bilirubin ≤1.5 upper limit of normal (ULN) (unless documented Gilbert's syndrome), aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤2.5 ULN (≤5 ULN in the presence of liver metastases).
10. Adequate liver function with bilirubin \<3 mg/dL and albumin \>2.5 g/dL.
11. Systolic blood pressure \<160 mmHg and diastolic blood pressure \<100 mmHg, as documented at baseline. Patients with hypertension are eligible if their hypertension is controlled and they meet all other eligibility criteria.
12. Adequate kidney function with a creatinine clearance \>30 mL/min (Cockcroft-Gault).
13. Patient with Eastern Cooperative Oncology group (ECOG) performance status (PS) ≤1.
14. Patient is willing to use contraceptive during and for at least 1 week after discontinuing darolutamide.
15. Patient affiliated to the social security system (or equivalent according to local regulations for participation in clinical trials).
16. Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.

Exclusion Criteria:

1. Patient previously treated for metastatic prostate cancer with a novel hormonal agent (NHA), a CYP17 inhibitor, ketoconazole, chemotherapy, or immunotherapy.
2. A history of cancer, other than the prostate cancer under study, within the 3 years prior to study inclusion, excluding cured localised cancer such as non-melanomatous skin cancer and non-muscle invasive bladder cancer.
3. Presence of an uncontrolled disease or affection that according to the investigator will hinder compliance with the trial procedures or requires hospitalisation.
4. Known to have active viral hepatitis, active human immunodeficiency virus (HIV) A at screening.
5. Patients with known allergy or severe hypersensitivity to the study treatment or any of its excipients.
6. Inability to swallow oral medications.
7. Gastrointestinal disorder or procedure that can be expected to interfere significantly with the absorption of study treatment.
8. Any of the following within 6 months before randomisation: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV.
9. Patients participating in another therapeutic trial within the 30 days prior to randomisation.
10. Patients unable to comply with trial obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the trial.
11. Person deprived of their liberty or under protective custody or guardianship.

Where this trial is running

Lorient and 3 other locations

• Groupe Hospitalier Bretagne Sud — Lorient, France (Recruiting)
• Centre Azuréen de Cancérologie — Mougins, France (Recruiting)
• CHU de Saint-Etienne — Saint-Etienne, France (Recruiting)
• Gustave Roussy Cancer Campus — Villejuif, France (Recruiting)

Study contacts

• Principal investigator: Ronan FLIPPOT, MD — Gustave Roussy (Villejuif, France)
• Study coordinator: Catherine LEGER

Conditions Prostatic Cancer, Castration-Resistant; Phase 3; International; Multicentric; Randomised; Stereotactic body radiation therapy; PET-PSMA; mCRPC