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

Prostate Cancer Clinical Trial

— OLIGOPELVIS2  

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03630666
• Other study ID #: ICO-N-2017-13
• Status: Active, not recruiting
• Phase: N/A
• Start date: December 4, 2018
• Est. completion date: June 2026

Study information

• Verified date: July 2023
• Source: Institut Cancerologie de l'Ouest
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 256
• Est. completion date: June 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Oligometastasis
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• IADT
Patient will receive one injection of IADT at randomization

Combination Product:
• IADT + radiotherapy
Patient will receive one injection of IADT at randomization then will receive irradiation 3 months after injection of IADT

Locations

Country	Name	City	State
France	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	Hopital Privé du Confluent	Nantes
France	Institut de Cancérologie	Nantes
France	Clinique Mutualiste de l'Estuaire	Saint-Nazaire
France	ICL Lucien Neuwirth	Saint-Priest-en-Jarez
France	Centre Saint Yves	Vannes

Sponsors (3)

Lead Sponsor	Collaborator
Institut Cancerologie de l'Ouest	Astellas Pharma Inc, Direction Générale de l'Offre de Soins

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression-free survival	PSA or CT scan	90 months
Secondary	overall survival	death	90 months
Secondary	time to castration-resistance	serum testosterone mesure	90 months
Secondary	toxicity to IADT and radiation	evaluation with NCI-CTC AE v4.03	90 months
Secondary	quality of life during treatment	questionnaire PR25	90 months
Secondary	quality of life during treatment	questionnaire EQ-5D-3L	90 months
Secondary	quality of life during treatment	questionnaire EORTC QLQ-C30 v3.0	90 months
Secondary	site of tumor progression	FCH or PSMA PET at biochemical relapse	90 months