Clinical trial NCT04115007: Prostate-cancer Treatment Using Stereotactic Radiotherapy for Oligometastases Ablation in Hormone-sensitive Patients
Official title: Prostate-cancer Treatment Using Stereotactic Radiotherapy for Oligometastases Ablation in Hormone-sensitive Patients - a GETUG-AFU Phase III Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Oligometastatic Hormone Sensitive Prostate Cancer
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2019-10-03
Enrollment: 550
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Castration-resistant prostate cancer free survival
timeFrame: From randomization to castration resistance or death from any cause, up to 1 year
Secondary outcomes:
measure: Overall survival
timeFrame: From randomization to death from any cause, up to 5 years
measure: Prostate cancer specific survival
timeFrame: From randomization to death from prostate cancer, up to 5 years
measure: Time to castration resistance
timeFrame: Time from randomization to castration resistance, up to 5 years
measure: Time to next symptomatic skeletal event
timeFrame: Time from randomization to the first symptomatic skeletal event, up to 5 years
measure: Time to next symptomatic skeletal event at the treated metastatic bone sites
timeFrame: Time from randomization to the first symptomatic skeletal event, 5 years
measure: Time to use of intermittent hormonal therapy
timeFrame: Time from randomization to the use of intermittent androgen deprivation therapy, up to 5 years
measure: Duration of intermittent hormonal therapy
timeFrame: From the end of continuous therapy to the end of intermittent therapy, up to 5 years
measure: Time to secondary treatments (local or systemic)
timeFrame: From randomization to initiation of secondary treatment, up to 5 years
measure: Acute and late toxicity of stereotactic radiotherapy of oligometastases: Adverse events
timeFrame: Throughout study completion, up to 5 years
measure: Severity of pain during treatment
timeFrame: 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
measure: The 3-level version of EQ-5D (EQ-5D-3L) questionnaire
timeFrame: 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)
measure: Expanded Prostate Cancer Index Composite (EPIC) short form
timeFrame: 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)
measure: Cost-effectiveness analysis of the proposed therapeutic strategy
timeFrame: At baseline, week 6, 3 months, 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, castration resistance (up to 5 years)
Other outcomes:
Locations:
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Bordeaux
country: France
facility: Institut Bergonié
city: Brest
country: France
facility: Centre d'oncologie - Clinique Pasteur
city: Brest
country: France
facility: CHRU de Brest
city: Caen
country: France
facility: Centre François Baclesse
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Creil
country: France
facility: Centre Amethyst de Creil
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal de Créteil
city: Jossigny
country: France
facility: Institut de cancérologie de Seine et Marne - Clinique de Jossiny
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lorient
country: France
facility: Groupe Hospitalier Bretagne Sud
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Mougins
country: France
facility: Centre Azureen de Cancerologie
city: Nantes
country: France
facility: Hôpital Privé du Confluent
city: Nantes
country: France
facility: ICO René Gauducheau
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institut Curie
city: Pierre-Bénite
country: France
facility: CHU Lyon Sud
city: Pringy
country: France
facility: CH Annecy
city: Reims
country: France
facility: Institut du Cancer Courlancy
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Rouen
country: France
facility: CHU de Rouen - Charles Nicole
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Gregoire
country: France
facility: CHP Saint Grégoire
city: Saint-Mandé
country: France
facility: HIA Begin
city: Saint-Étienne
country: France
facility: Institut de cancérologie et d'hématologie universitaire de Saint Etienne
city: Sarcelles
country: France
facility: Institut de Cancerologie Paris Nord
city: Strasbourg
country: France
facility: Institut de cancérologie Strasbourg Europe (ICANS )
city: Toulouse
country: France
facility: IUCT- Oncopole -Institut Claudius Regaud
city: Toulouse
country: France
facility: Clinique PASTEUR
city: Valence
country: France
facility: Centre de radiothérapie Marie Curie de Valence
city: Versailles
country: France
facility: Centre Amethyst - Oncologie 78
city: Villejuif
country: France
facility: Gustave Roussy Cancer Campus Grand Paris
city: Fort-de-France
country: Martinique
facility: CHU Martinique
Study officials:
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Pierre BLANCHARD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Petrelli F, Ghidini A, Ghidini M, Bukovec R, Trevisan F, Turati L, Indini A, Seghezzi S, Lonati V, Moleri G, Tomasello G, Zaniboni A. Better survival of patients with oligo- compared with polymetastatic cancers: a systematic review and meta-analysis of 173 studies. F1000Res. 2021 May 27;10:423. doi: 10.12688/f1000research.52546.4. eCollection 2021.