Combination of Darolutamide and Stereotactic Body Radiation Therapy in Patients With Castration Resistant Prostate Cancer and Oligometastases on Functional Imaging
In earlier stages of prostate cancer, male sexual hormones (androgens) stimulate the growth of cancer cells. Castration-resistant prostate cancer (CRPC) means that the prostate cancer continued to grow despite patients are taking hormone therapy to control the disease. One of the standard treatments for these patients is so-called 'new generation' hormonal therapy. These hormone therapies include apalutamide, enzalutamide, or darolutamide. They work by blocking androgen receptors that play an important role in the growth of prostate cancer. In the case of oligometastatic CRPC, the cancer has gone beyond the prostate and has spread to other organs in the body (metastases), but these metastases remain limited in number. An early detection of the oligometastatic CRPC and appropriate treatment may prolong survival in these patients. The treatment proposed as part of this research is a combination of oral darolutamide, approved in Europe to treat patients with CRPC who do not have metastasis visible on CT-scan or bone scintigraphy (but visible with positron emission tomography-scan (PET-Scan), a more precise imaging technique) with stereotactic body radiotherapy (SBRT), a new radiotherapy technique guided by very high precision medical imaging. This method makes it possible to better target cancer cells while preserving neighboring healthy organs. The principal objective of this trial is to evaluate the efficacy of the combination of SBRT with darolutamide, compared to darolutamide.
• 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.
• Patients aged ≥18 years.
• Patient with histologically confirmed of adenocarcinoma prostate cancer without small cell or pure endocrine features.
• Patient with a history of local treatment with curative intent for localised prostate cancer, including surgery or radiotherapy.
• 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.
• Detection of 1 to 5 metastatic sites (pelvic lymph nodes included) on new generation PET using either choline, fluciclovine, or PSMA as tracer.
• All metastatic sites must be amenable to stereotactic radiation therapy.
• 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.
• 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).
⁃ Adequate liver function with bilirubin \<3 mg/dL and albumin \>2.5 g/dL.
⁃ 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.
⁃ Adequate kidney function with a creatinine clearance \>30 mL/min (Cockcroft-Gault).
⁃ Patient with Eastern Cooperative Oncology group (ECOG) performance status (PS) ≤1.
⁃ Patient is willing to use contraceptive during and for at least 1 week after discontinuing darolutamide.
⁃ Patient affiliated to the social security system (or equivalent according to local regulations for participation in clinical trials).
⁃ 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.