Prostate-cancer Treatment Using Stereotactic Radiotherapy for Oligometastases Ablation in Hormone-sensitive Patients

Phase 3Active Not RecruitingNCT04115007

UNICANCER550 enrolled

Overview

INDICATION: Oligometastatic hormone-sensitive prostate cancer patients. METHODOLOGY: Open label, double arm, randomized 1:1, multicenter phase III study. PRIMARY OBJECTIVE: To assess the efficacy of ablative radiotherapy (SBRT applied to all oligometastases) administered to all gross tumor sites (metastases and prostate if applicable), in oligometastatic hormone-sensitive prostate cancer patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

550

Conditions

Oligometastatic Hormone Sensitive Prostate Cancer

Interventions

Stereotactic Body Radiotherapy (SBRT) + Standard of careRADIATION

Definition of standard of care (prior to randomization): * Radiotherapy to the prostate in de novo metastatic patients * Radiotherapy to the pelvic lymph nodes in patients with positive pelvic nodes (given as full dose to the positive lymph node and prophylactic dose to the pelvic nodal basin) * Long term ADT +/- intermittent treatment * Additional therapy following tumor board meeting : new generation hormonal therapy (abiraterone, enzalutamide, apalutamide or other approved) or chemotherapy (docetaxel). SBRT is delivered using the following regimen: 30 Grays (10 Gy x 3 fractions) for axial and appendicular bones and lymph node metastases if present. In case the dose cannot be safely delivered while maintaining a safe dose to the organs at risk, an alternate regimen (35 Gy in 5 fractions of 7 Gy) can be used.

Standard of careDRUG

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

DIAGNOSIS AND INCLUSION CRITERIA: 1. Histologically proven adenocarcinoma of the prostate (any T stage, Gleason score, or prostate specific antigen (PSA) level); 2. Defined as M1 based on the presence of at least one bone metastasis; 3. Diagnostic workup including functional imaging (F or C-Choline-PET/CT or prostate specific membrane antigen (PSMA) PET/CT or whole body MRI) - done prior to the start of hormonal therapy; 4. With up to 5 asymptomatic or paucisymptomatic metastatic sites including at least one bone +/- pulmonary lesion +/- nodal mestastases. Are counted as a "separate" metastatic site : * each bone lesion, whatever the location (including pelvic localization), except if two lesions show hyperfixation in the same bone and are located \< 1cm from each other they can be counted as one lesion * each node or nodal area located outside the true pelvis with a small diameter of 1cm or greater or with univoqual abnormal function imaging (PET Scan hyperfixation or hypersignal in whole body MRI); if multiple nodes are in close vicinity (\<1cm distance between them and \<4cm in total distance including the nodes, amenable to one SBRT treatment) they can be counted as one lesion * and patients with lung metastasis can be included 5. Patients with a previous prostatectomy or radiotherapy to the prostate and/or pelvic lymph nodes are eligible provided they have no active disease within the irradiated areas, based on functional imaging findings; 6. Age ≥18 years; 7. Eastern Cooperative Oncology Group (ECOG) ≤2; 8. Suitable for long term anti androgen therapy; 9. Patient not suitable for docetaxel or abiraterone can be included; 10. Patient that have started long term hormonal therapy are eligible if hormonal therapy has been initiated less than 2 months before randomization; 11. Patients must agree to use adequate contraception methods for the duration of study treatment and for 6 months after completing treatment; 12. Patient must have received the information sheet and signed the consent form; 13. Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures; 14. Patient must be affiliated to the social security system. NON-INCLUSION CRITERIA: 1. Patient with more than 5 metastatic sites; 2. Patient with isolated Rib hyperfixation on functional imaging without a clear correlate on morphological imaging; 3. Patient with metastatic sites other than bone, lymph nodes or lung; 4. Metastases not amenable to radiotherapy treatment with high/curative doses by multidisciplinary meeting \[i.e. SBRT as per protocol or curative doses using moderate hypofractionation (55-60Gy/20) or conventional fractionation (≥74 Gy)\] (e.g. gross epidural involvement, involvement of three contiguous vertebral bodies, major soft tissue involvement, and previous radiation treatment); 5. Metastases requiring immediate treatment due to significant pain (use of opioid medication), or at risk of fracture or neurological deficit; 6. Prior radiotherapy or focal ablative treatment (cryotherapy, radiofrequency ablation,…) to metastatic lesions; 7. Patients previously treated by Hormonotherapy with castrate testosterone level \<50 ng/dL or ≤0.50 ng/mL or 1.73 nmol/L prior use of ADT; 8. Prior invasive (except non-melanoma skin cancer) malignancy unless disease-free for ≥5 years; 9. Contra-indication to MRI (needed for spinal SBRT); 10. Persons deprived of their liberty or under protective custody or guardianship; 11. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons; 12. Participation in another therapeutic trial within 30 days prior to randomization.

Locations (35)

Outcomes

Primary Outcomes

Castration-resistant prostate cancer free survival

Castration-resistant prostate cancer free survival, defined as the time from randomization to castration resistance or death from any cause. Castration resistance is defined as either biochemical progression or radiological progression, with serum testosterone being at a castrated level (\<50 ng/dL or \<1.7 nmol/L).

Time frame: From randomization to castration resistance or death from any cause, up to 1 year

Secondary Outcomes

Overall survival

The overall survival is the length of time from randomization that patients enrolled in the study are still alive. The outcome is to evaluate whether SRBT improves overall survival compared to standard of care

Time frame: From randomization to death from any cause, up to 5 years

Prostate cancer specific survival

To evaluate, compared to standard of care, whether SRBT improves survival of patients until death from prostate cancer

Time frame: From randomization to death from prostate cancer, up to 5 years

Time to castration resistance

The length of time patients leave without resistance to castration treatment, where deaths occurring with no castration resistance (i.e. unrelated to prostate cancer) are censored

Time frame: Time from randomization to castration resistance, up to 5 years

Time to next symptomatic skeletal event

The length of time until manifestation of the first symptomatic skeletal event among the following: symptomatic bone fracture, surgery to bone or use of palliative radiotherapy to bone

Time frame: Time from randomization to the first symptomatic skeletal event, up to 5 years

Time to next symptomatic skeletal event at the treated metastatic bone sites

Data from ClinicalTrials.gov

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