Comparison of Intermittent Androgen Deprivation Therapy With or Without Irradiation Recovery in Prostate Cancer Patients

NCT ID: NCT03630666

Last Updated: 2025-08-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 256 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-04
• Study Completion Date: 2026-06-30

Brief Summary

Metastatic prostate cancer has traditionally been regarded as an incurable dissemination of disease, and treatment is focused on delaying progression rather than eliminating all tumor burden. Local therapies, and specifically radiotherapy, have been directed at quality of life endpoints and not at improving survival. However, advances in imaging and systemic therapy have identified a population of 'oligometastatic' patients who have a lower burden of metastatic disease (usually ≤5 lesions), who may present an exception. This condition is hypothesized to occupy the hinterland between incurable metastatic disease and locoregional disease, where micrometastatic disease is assumed to exist and yet remain eradicable. Oligometastases can be detected using standard imaging but the sensitivity of these exams is very low for patients with a PSA below 10 ng/ml. In France, FCH PET imaging is now routinely available in a large majority of cancer centres. More recently, PSMA PET imaging has been developed.

Since most oligometastases are now discovered at a time when conventional imaging is unable to detect metastases, we must rely on the literature regarding purely biochemically-relapsing prostate cancer patients. Three strategies have been explored: (i) observation until symptoms develop, (ii) early intermittent Androgen Deprivation Therapy (IADT) and (iii) continuous Androgen Deprivation Therapy (ADT). Recent data suggest that, of the three strategies, early intermittent ADT was superior in term of overall survival to observation in controlling metastatic prostate cancer, and this effect was similar in the biochemically-relapsing prostate cancer patient population.

This phase III study will explore the role of salvage pelvic IG-IMRT combined with intermittent ADT (IADT) in pelvic oligometastatic patients in prolonging the first failure-free interval between the first and the second intermittent ADT courses.

Detailed Description

Screening procedures will be performed up to three months before starting IADT. After obtaining informed consent, patients will be randomly allocated to one of two groups:

Experimental group: IADT + IG-IMRT Control group: IADT

In both study arms, the first injection of IADT will be administered in hospital on the day of randomization. The overall duration of IADT will be six months.

In the experimental group, patients will receive radiotherapy three months after the first injection of IADT.

The overall duration of radiotherapy will be three months.

The overall duration of IADT will be six months. It will be administered three months, +/- 15 days prior to the first day of radiotherapy. At the completion of the six-month treatment period, a non-treatment interval will start if :

there is no evidence of clinical disease progression and the PSA level is ≤ 4.00 ng/ml If the PSA subsequently rises above 0.20 ng/ml and is confirmed by a second measurement at least three weeks later, PET/CT imaging will be repeated every 6 months until a clinical failure is detected or until the PSA rises above 4.00 ng/ml.

Conditions

Prostate Cancer; Oligometastasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IADT - Intermittent Androgen Deprivation Therapy

one injection of IADT. The overall duration of IADT will be six months.

Group Type: ACTIVE_COMPARATOR

IADT

Intervention Type: DRUG

Patient will receive one injection of IADT at randomization

IADT + Radiotherapy (Intermittent Androgen Deprivation Therapy plus Radiotherapy)

One injection of IADT. The overall duration of IADT will be six months. Irradiation three months after injection of IADT. The overall duration of radiotherapy will be three months.

Group Type: EXPERIMENTAL

IADT + radiotherapy

Intervention Type: COMBINATION_PRODUCT

Patient will receive one injection of IADT at randomization then will receive irradiation 3 months after injection of IADT

Interventions

IADT

Patient will receive one injection of IADT at randomization

Intervention Type: DRUG

IADT + radiotherapy

Patient will receive one injection of IADT at randomization then will receive irradiation 3 months after injection of IADT

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

LH-RH (Luteinizing Hormone Releasing Hormone) agonist; IG-IMRT; LH-RH (Luteinizing Hormone Releasing Hormone) agonist

Eligibility Criteria

Inclusion Criteria

• Histologically-proven prostate adenocarcinoma
• Age ≥ 18 years
• Performance Status 0-1
• Prior radical prostate treatment (surgery and/or radiotherapy)
• ≤ 5 metastatic pelvic lymph nodes detected by FCH-PET or PSMA-PET
• Upper limit of metastatic lymph nodes: aortic bifurcation
• If ADT has been previously administered to the patient, at least 12 months must have elapsed between the predicted duration of the last injection and inclusion of the patient in the study. For this category of patients, serum testosterone must be higher than 6 nmol/L (50 ng/L) prior to inclusion
• Biochemical relapse (according to the European Association of Urology guidelines) is defined by :

Following radical prostatectomy (RP), biochemical recurrence (BCR) is defined by two consecutive rising PSA values > 0.20 ng/ml After primary radiation therapy (RT), the Radiation Therapy Oncology Group (RTOG) and American Society for Radiation Oncology Phoenix Consensus Conference definition of PSA failure is any PSA increase > 2.00 ng/ml higher than the PSA nadir value, regardless of the serum concentration of the nadir.

• Having given written informed consent prior to any procedure related to the study.
• Patient is willing and able to comply with the protocol for the duration of the study including all scheduled treatment, visits and examinations.
• Patient has valid health insurance
• Subjects who have partners of childbearing potential must be willing to use a method of effective birth control during treatment and for 12 months following completion of treatment with ADT or IG-IMRT.

Exclusion Criteria

• Bone or visceral metastases
• Para-aortic lymph node metastases (above the aortic bifurcation)
• Presence of more than five metastatic lymph nodes
• Evidence of local intra-prostatic relapse
• Evidence of prostate bed relapse in a previously irradiated region. Prostate bed relapses which have not been previously irradiated will not be excluded
• Evidence of metastasis at initial diagnosis
• Evidence of distant metastases beyond the pelvic lymph nodes
• Previous irradiation of pelvic lymph nodes
• Castration-resistant prostate cancer (CRPC) as defined by : a castrate serum testosterone < 6 nmol/L (50 ng/L)
• Contraindications to pelvic irradiation (e.g. chronic inflammatory bowel disease)
• Contraindications to ADT (known hypersensitivity to any of the study drugs or excipients)
• Severe uncontrolled hypertension defined as systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy
• Other malignancy treated within the last 5 years (except non-melanoma skin cancer)
• Patients with a biochemical relapse while on active treatment with LHRH-agonist, LHRH-antagonist, anti-androgen, maximal androgen blockade, or oestrogen
• Treatment during the past month with products known to influence PSA levels (such as finasteride)
• In case of previous prostate/prostate bed radiotherapy, PET-positive lymph nodes have to be located outside the previous irradiation field with a maximum of 20 Gy to the PET-positive lymph nodes region
• Patients already included in another therapeutic trial with an experimental drug or having been given an experimental drug within a period of 30 days
• Disorder precluding understanding of trial information or informed consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Direction Générale de l'Offre de Soins

OTHER_GOV

Sponsor Role: collaborator

Astellas Pharma Inc

INDUSTRY

Sponsor Role: collaborator

Institut Cancerologie de l'Ouest

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

STEPHANE SUPIOT, MD

Role: PRINCIPAL_INVESTIGATOR

Institut de Cancérologie de l'Ouest

Locations

Institut Sainte Catherine

Avignon, , France

Institut Bergonie

Bordeaux, , France

CHRU de Brest

Brest, , France

Clinique Pasteur

Brest, , France

Institut de Cancérologie de Bourgogne

Chalon-sur-Saône, , France

Centre Jean Perrin

Clermont-Ferrand, , France

Centre Georges François Leclerc

Dijon, , France

Centre Oscar Lambret

Lille, , France

Centre Léon Bérard

Lyon, , France

Institut de Cancérologie de Montpellier

Montpellier, , France

Centre Azureen de Cancerologie

Mougins, , France

Institut de Cancérologie

Nantes, , France

Hopital Privé du Confluent

Nantes, , France

Clinique Mutualiste de l'Estuaire

Saint-Nazaire, , France

ICL Lucien Neuwirth

Saint-Priest-en-Jarez, , France

Centre Saint Yves

Vannes, , France

Countries

France

Other Identifiers

ICO-N-2017-13

Identifier Type: -

Identifier Source: org_study_id