Clinical trial NCT03630666: Comparison of Intermittent Androgen Deprivation Therapy With or Without Irradiation Recovery in Prostate Cancer Patients
Official title: A Study Comparing Intermittent Androgen Depriving Therapy With Or Without Salvage High-Dose Intensity Modulation Radiotherapy (IG-IMRT)To Oligometastatic Pelvic Lymph Nodes In Biochemically-relapsing Prostate Cancer Patients.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Prostate Cancer
Oligometastasis
Keywords: Oligometastatic pelvic lymph nod, IADT, radiotherapy
Lead sponsor: Institut Cancerologie de l'Ouest
Sponsor class: OTHER
Collaborators: name: Direction Générale de l'Offre de Soins
name: Astellas Pharma Inc
First posted: 2018-08-15
Enrollment: 256
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: phase 3 study, randomised, open
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: progression-free survival
timeFrame: 90 months
Secondary outcomes:
measure: overall survival
timeFrame: 90 months
measure: time to castration-resistance
timeFrame: 90 months
measure: toxicity to IADT and radiation
timeFrame: 90 months
measure: quality of life during treatment
timeFrame: 90 months
measure: quality of life during treatment
timeFrame: 90 months
measure: quality of life during treatment
timeFrame: 90 months
measure: site of tumor progression
timeFrame: 90 months
Other outcomes:
Locations:
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Bordeaux
country: France
facility: Institut Bergonie
city: Brest
country: France
facility: CHRU de Brest
city: Brest
country: France
facility: Clinique Pasteur
city: Chalon-sur-Saône
country: France
facility: Institut de Cancérologie de Bourgogne
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: Montpellier
country: France
facility: Institut de Cancérologie de Montpellier
city: Mougins
country: France
facility: Centre Azureen de Cancerologie
city: Nantes
country: France
facility: Institut de Cancérologie
city: Nantes
country: France
facility: Hopital Privé du Confluent
city: Saint-Nazaire
country: France
facility: Clinique Mutualiste de l'Estuaire
city: Saint-Priest-en-Jarez
country: France
facility: ICL Lucien Neuwirth
city: Vannes
country: France
facility: Centre Saint Yves
Study officials:
affiliation: Institut de Cancérologie de l'Ouest
name: STEPHANE SUPIOT, MD
role: PRINCIPAL_INVESTIGATOR
References: