Oligometastatic Hormone Sensitive Prostate Cancer Clinical Trial
— Oligo-PRESTOOfficial title:
Prostate-cancer Treatment Using Stereotactic Radiotherapy for Oligometastases Ablation in Hormone-sensitive Patients - a GETUG-AFU Phase III Randomized Controlled Trial
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.
| Status | Recruiting |
| Enrollment | 550 |
| Est. completion date | February 28, 2031 |
| Est. primary completion date | June 23, 2026 |
| Accepts healthy volunteers | No |
| Gender | Male |
| Age group | 18 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| France | Institut Sainte Catherine | Avignon | |
| France | Institut Bergonié | Bordeaux | |
| France | Centre d'oncologie - Clinique Pasteur | Brest | |
| France | CHRU de Brest | Brest | |
| France | Centre François Baclesse | Caen | |
| France | Centre Jean Perrin | Clermont-Ferrand | |
| France | Centre Amethyst de Creil | Creil | |
| France | Centre Hospitalier Intercommunal de Créteil | Créteil | |
| France | Institut de cancérologie de Seine et Marne - Clinique de Jossiny | Jossigny | |
| France | Centre Oscar Lambret | Lille | |
| France | Groupe Hospitalier Bretagne Sud | Lorient | |
| France | Centre Leon Berard | Lyon | |
| France | Institut Paoli Calmettes | Marseille | |
| France | Centre Azureen de Cancerologie | Mougins | |
| France | Hôpital Privé du Confluent | Nantes | |
| France | ICO René Gauducheau | Nantes | |
| France | Centre Antoine Lacassagne | Nice | |
| France | Institut Curie | Paris | |
| France | CHU Lyon Sud | Pierre-Bénite | |
| France | CH Annecy | Pringy | |
| France | Institut du Cancer Courlancy | Reims | |
| France | Centre Eugene Marquis | Rennes | |
| France | Centre Henri Becquerel | Rouen | |
| France | CHU de Rouen - Charles Nicole | Rouen | |
| France | CHP Saint Grégoire | Saint Gregoire | |
| France | Institut de cancérologie et d'hématologie universitaire de Saint Etienne | Saint-Étienne | |
| France | HIA Begin | Saint-Mandé | |
| France | Institut de Cancerologie Paris Nord | Sarcelles | |
| France | Institut de cancérologie Strasbourg Europe (ICANS ) | Strasbourg | |
| France | Clinique PASTEUR | Toulouse | |
| France | IUCT- Oncopole -Institut Claudius Regaud | Toulouse | |
| France | Centre de radiothérapie Marie Curie de Valence | Valence | |
| France | Centre Amethyst - Oncologie 78 | Versailles | |
| France | Gustave Roussy Cancer Campus Grand Paris | Villejuif | |
| Martinique | CHU Martinique | Fort-de-France |
| Lead Sponsor | Collaborator |
|---|---|
| UNICANCER |
France, Martinique,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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). | From randomization to castration resistance or death from any cause, up to 1 year | |
| Secondary | 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 | From randomization to death from any cause, up to 5 years | |
| Secondary | Prostate cancer specific survival | To evaluate, compared to standard of care, whether SRBT improves survival of patients until death from prostate cancer | From randomization to death from prostate cancer, up to 5 years | |
| Secondary | 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 from randomization to castration resistance, up to 5 years | |
| Secondary | 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 from randomization to the first symptomatic skeletal event, up to 5 years | |
| Secondary | Time to next symptomatic skeletal event at the treated metastatic bone sites | The length of time until manifestation of the first symptomatic skeletal event, at a site irradiated during the study for patients in the experimental arm, among the following: symptomatic bone fracture, the use of bone surgery, or palliative bone radiotherapy and spinal cord compression | Time from randomization to the first symptomatic skeletal event, 5 years | |
| Secondary | Time to use of intermittent hormonal therapy | The length of time patients receive continuous androgen deprivation therapy before the switch to the intermittent androgen deprivation therapy | Time from randomization to the use of intermittent androgen deprivation therapy, up to 5 years | |
| Secondary | Duration of intermittent hormonal therapy | The length of time patients receive intermittent androgen deprivation therapy | From the end of continuous therapy to the end of intermittent therapy, up to 5 years | |
| Secondary | Time to secondary treatments (local or systemic) | The interval between the randomization and the initiation of the first treatment after disease progression: systemic chemotherapy, second line hormonal therapy, bone directed treatment (bisphosphonate or denosumab), or the use an antalgic palliative bone treatment (interventional radiology or radiotherapy) | From randomization to initiation of secondary treatment, up to 5 years | |
| Secondary | Acute and late toxicity of stereotactic radiotherapy of oligometastases: Adverse events | The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale will assess the severity of sensory neuropathic disorders, this derivative into 5 grades determined by the investigator. | Throughout study completion, up to 5 years | |
| Secondary | Severity of pain during treatment | The Brief Pain Inventory (BPI) questionnaire rapidly assesses the severity of pain and its impact on functioning. This self-report questionnaire includes:
A body schema The maximum pain, lowest pain, usual pain within the last 15 days (Numerical Numeric rating scales (NRS) 0 to 10 Description of current analgesic treatment An assessment of relief by a percentage scale (0-100%), Assessment of the impact of pain on: mood, relationships with others, walking, sleep, work, happiness the joy - of living, recreation, activities in general (digital scales, rating from 0 [normal] to 10 [no activity]). |
At baseline before radiotherapy, week 6, and at every follow-up (every three months for the first three years then every 6 months for the last two years after randomization), up to 5 years | |
| Secondary | The 3-level version of EQ-5D (EQ-5D-3L) questionnaire | This self-reported questionnaire that assesses the health-related quality of life of cancer patients in clinical trials consists of a descriptive system and a visual analogue scale (VAS).
The EQ-5D-3L descriptive system comprises five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each dimension has 3 levels (1 = "no problems", 2 = "some problems", and 3 = "extreme problems"). This questionnaire provide a 5-digit score which generate a health state profile. The VAS records the patient's self-rated health on a vertical visual analogue scale where the score range from 0 (Best imaginable health state) to 100 (Worst imaginable health state). The VAS is used as a quantitative measure of health outcome that reflects the patient's own judgement. |
At baseline, week 6, 3 months, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, and at castration resistance (up to 5 years) | |
| Secondary | Expanded Prostate Cancer Index Composite (EPIC) short form | This self-reported questionnaire, designed to evaluate patient function and bother after prostate cancer treatment, contains 26 item divided in 5 domains (Urinary Incontinence, Urinary Irritative/Obstructive, Bowel, Sexual, and Hormonal). Response options for each EPIC item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health-related quality of life. | At baseline, week 6, 3 months, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, and at castration resistance (up to 5 years) | |
| Secondary | Cost-effectiveness analysis of the proposed therapeutic strategy | To evaluate the economic cost of the SBRT treatment as compared to the treatment without radiotherapy in terms of cost assessments, incremental cost-effectiveness ratio and quality of life adjusted life years | At baseline, week 6, 3 months, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, castration resistance (up to 5 years) |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Not yet recruiting |
NCT05717660 -
APalutamiAPalutamide and stEReotactic Body Radiation Therapy for Metastatic Prostate Cancer
|
Phase 2 |