Evaluation of Darolutamide Combined with Stereotactic Body Radiation Therapy in Castration-Resistant Prostate Cancer with Oligometastases Detected by Functional Imaging
- Trial ID
- 2023-507482-26-00
- Protocol
- UC-GTG-2306
- Sponsor
- Unicancer
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate whether **stereotactic radiation therapy** combined with **darolutamide** is superior in terms of radiographic progression-free survival (rPFS) compared to darolutamide alone in patients with castration-resistant prostate cancer (CRPC) with 1 to 5 oligometastases, as detected by choline/fluciclovine or PSMA PET. This is clinically relevant as improving rPFS can potentially delay disease progression and improve patient outcomes in this population.
Secondary objectives include:
- Assessing the safety and tolerance of the combination therapy compared to darolutamide alone, using the NCI-CTCAE 5.0 criteria.
- Evaluating the efficacy of the combination therapy in terms of overall survival, time to treatment failure, prostate cancer-specific survival, time to PSA progression, biochemical response rate, time to next symptomatic skeletal event, and time to pain progression.
- Assessing the quality of life (QoL) of patients using the FACT-P questionnaire.
Participants
The clinical trial involves **male** participants diagnosed with **castrate-resistant prostate cancer** with oligometastases, as identified through functional imaging techniques such as PSMA or choline/fluciclovine-positron-emission tomography. The study population is composed of individuals aged 18 years and older, with no upper age limit specified. Participants are required to have a histologically confirmed diagnosis of adenocarcinoma prostate cancer, excluding small cell or pure endocrine features, and must have undergone local treatment with curative intent, such as surgery or radiotherapy. The trial does not include a vulnerable population, and only male subjects are eligible. Participants must demonstrate adequate liver and kidney function, controlled blood pressure, and normal hematological parameters. Lifestyle considerations include the willingness to use contraceptives during and after the trial period. The sponsor has not provided information regarding the total number of participants in the study.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of combining **darolutamide** with stereotactic body radiation therapy in patients diagnosed with castration-resistant prostate cancer (CRPC) with oligometastases. This study is a randomized, double-blind, controlled trial, aiming to assess the superiority of the combination therapy over darolutamide alone in terms of radiographic progression-free survival (rPFS). The trial is expected to commence recruitment on May 6, 2024, and conclude by May 6, 2032, with an estimated duration of participant involvement of up to 96 weeks, depending on the treatment arm and individual response.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as adequate liver and kidney function, controlled blood pressure, and a confirmed diagnosis of CRPC with 1 to 5 oligometastatic sites. Following successful screening, participants will be randomized into treatment groups. Regular follow-up visits will be scheduled to monitor safety, treatment adherence, and efficacy outcomes, including overall survival, time to treatment failure, and quality of life assessments. The end-of-study visit will occur after the completion of the treatment period or upon early termination.
Early termination from the study may occur if participants experience unacceptable adverse events, withdraw consent, or if the investigator deems it necessary for the participant's safety. The trial will adhere to rigorous safety monitoring, with adverse events graded according to the NCI CTCAE v5.0. The primary endpoint is the assessment of rPFS, while secondary endpoints include safety, overall survival, and other efficacy measures. Participants will be required to comply with the protocol, including the use of contraceptives during and after the trial, and must be affiliated with a social security system or equivalent.
Treatment
The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. **DEGARELIX** is utilized in the study as a **powder and solvent for solution for injection**. It is administered via the **subcutaneous** route. The maximum daily dose is 240 mg, with a total maximum dose of 7.68 g over a treatment period of up to 96 weeks. The active substance, degarelix, is a protein of non-chemical origin.
**NUBEQA 300 mg film-coated tablets**, containing the active substance **DAROLUTAMIDE**, are administered orally. The maximum daily dose is 1200 mg, with a total maximum dose of 2190 g over a 60-week treatment period. This medication is chemically derived and is used as a standard-of-care therapy in the trial.
**GOSERELIN** is provided as an **implant in a pre-filled syringe** for **subcutaneous use**. The maximum daily dose is 10.8 mg, with a total maximum dose of 345.6 mg over a 96-week treatment period. Goserelin is a protein of non-chemical origin.
**LEUPRORELIN ACETATE** is administered as a **powder and solvent for suspension for injection** via the **subcutaneous** route. The maximum daily dose is 22.5 mg, with a total maximum dose of 720 mg over a 96-week treatment period. This substance is chemically derived.
**TRIPTORELIN** is provided as a **powder and solvent for prolonged-release suspension for injection**. It can be administered either **intramuscularly or subcutaneously**. The maximum daily dose is 11.25 mg, with a total maximum dose of 360 mg over a 96-week treatment period. The origin of the active substance is not specified.
**BAY 1841788**, another formulation of **DAROLUTAMIDE**, is administered as a **film-coated tablet** orally. The dosing schedule is similar to NUBEQA, with a maximum daily dose of 1200 mg and a total maximum dose of 2190 g over a 60-week treatment period. This formulation is also chemically derived and serves as a comparator treatment in the trial.
Efficacy
Efficacy in this clinical trial will be assessed primarily through the measurement of **radiographic progression-free survival (rPFS)**. This endpoint will evaluate the superiority of stereotactic body radiation therapy combined with darolutamide compared to darolutamide alone in patients with castration-resistant prostate cancer (CRPC) who have 1 to 5 oligometastases. Secondary efficacy assessments will include overall survival (OS), time to treatment failure (TTF), prostate cancer-specific survival, time to PSA progression, biochemical response rate, time to next symptomatic skeletal event (SSE), time to pain progression, and quality of life. These parameters will be measured and analyzed at various timepoints throughout the trial, using validated scales and laboratory tests where applicable. The trial will adhere to a structured schedule for data collection and analysis to ensure the reliability and validity of the efficacy outcomes.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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 with with a combination of Castrate level of testosterone: testosterone < 50ng/dl or 1.7 nmol/L. AND at least one of the following conditions: An increasing PSA level, confirmed in 3 consecutive assessments performed at least 1 week apart despite androgen deprivation therapy; • 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.
- 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 10^9/L, platelets count ≥100 x 10^9/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), ASAT and ALAT ≤2.5 ULN (≤5 ULN in the presence of liver metastases).
- 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.
Exclusion Criteria
- Patient previously treated for metastatic castrate-resistant prostate cancer with chemotherapy or immunotherapy. Patients who received prior NHA are eligible provided: - they did not progress on previous NHA - they progressed on previous NHA and chemotherapy is not indicated by investigator
- 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.
- Presence of an uncontrolled disease or affection that according to the investigator will hinder compliance with the trial procedures or requires hospitalisation.
- Known to have active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease at screening
- Patients with known allergy or severe hypersensitivity to the study treatment or any of its excipients.
- Inability and/or difficulty to swallow oral medications.
- Gastrointestinal disorder or procedure that can be expected to interfere significantly with the absorption of study treatment.
- 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.
- Patients participating in another therapeutic trial within the 30 days prior to randomisation.
- 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.
- Person deprived of their liberty or under protective custody or guardianship.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Yet Recruiting | 06 May 2024 | 23 |
 France | Recruiting | 06 May 2024 | 195 |
 Ireland | Not Yet Recruiting | 06 May 2024 | 19 |
 Spain | Not Yet Recruiting | 06 May 2024 | 50 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
TRIPTORELIN | Other | — | INTRAMUSCULAR OR SUBCUTANEOUS | 11.25 | 96 | SUB11324MIG |
BAY 1841788 | Test | FILM-COATED TABLET | ORAL | 1200 | 60 | PRD1849573 |
LEUPRORELIN ACETATE | Other | — | SUBCUTANEOUS | 22.5 | 96 | SUB02900MIG |
GOSERELIN | Other | — | SUBCUTANEOUS USE | 10.8 | 96 | SUB07962MIG |
NUBEQA 300 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 1200 | 60 | PRD7991449 |
DEGARELIX | Other | — | SUBCUTANEOUS | 240 | 96 | SUB27748 |