Relapse in Previously Irradiated Prostate Bed : Stereotactic Ablative Reirradiation Potentiated by Metformin

• Status: Recruiting
• Trial end date: 2028-11-01
• Target enrollment: 0
• Participant gender: Male

Summary

This phase I/II escalation dose study is assessing the efficacy of the recommended dose of stereotactic re-irradiation (SBRT) of relapses within the prostatectomy bed, potentiated by metformin

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institut Cancerologie de l'Ouest
• Treatments: Metformin

Criteria

Inclusion Criteria:

• Written informed consent according to International Conference on Harmonisation (ICH)/ Good Clinical Practice (GCP) regulations before registration and prior to any trial specific procedures.

• Biochemical recurrence occurring at least 2 years after external radiotherapy of the prostate lodge and/or the end of hormone therapy, for prostatic adenocarcinoma previously treated by radical prostatectomy.

• Local recurrence in irradiated areas proven by biological (PSA > 0.2 ng/ml and ascending confirmed by 2 successive assays) and radiological (lesion visible on MRI and/or Choline PET and/or Prostate-Specific Membrane Antigen (PSMA) PET) or histological examinations.

• Recurrence without rectal invasion

• Remote recurrence from vesico-urethral anastomosis (> 10 mm) to limit urinary toxicity

• Macroscopic Target Volume (GTV) ≤ 27cm3 to limit toxicity

• Pelvic and prostate MRI evaluation

• Absence of pelvic lymph node or metastatic recurrence proven by choline PET or PSMA PET scan

• World Health Organisation (WHO) performance status 0-1

• PSA ≤ 10 ng / ml

• PSA doubling time > 6 months

• No anti-cancer treatments planned for the current relapse, including hormone therapy.

• Age > 18 years old.

• Life expectancy greater than or equal to 5 years.

• Patient registered with a health insurance system.

• Patients willing and able to comply with the planned visits, treatment plan, laboratory tests and other study procedures indicated in the protocol.

Exclusion Criteria:

• Metastatic disease (bone, lymph node or other)

• Late radiotherapy urinary or gastrointestinal toxicity (grade ≥ 2) (after radiotherapy of prostate lodge)

• History of cancer in the 5 years prior to trial entry other than cutaneous basal cell carcinoma

• Inflammatory bowel disease

• Contraindications for performing MRI

• Volume of the GTV > 27 cm3

• Presence of grade 3 rectal telangiectasia classified by the Vienna Rectoscopy score (Rectoscopy required) (Appendix 7)

• Rectal surgery history

• Diabetic patient with HBA1C > laboratory normal value

• Creatinine clearance < 45 mL/min

• Treatment with metformin in the last 3 months prior to inclusion

• Severe comorbidity that may affect treatment, for example :

• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of inclusion.

• Unstable angina, myocardial infarction and/or congestive heart failure requiring hospitalization within the last 6 months

• Myocardial infarction in the last 6 months.

• Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) or other respiratory conditions requiring hospitalization or preventing metformin therapy at the time of inclusion.

• Any condition associated with an increased risk of lactic acidosis (e.g., alcohol abuse, New York Heart Association (NYHA) III or IV congestive heart failure).

• Clinically significant history of hepatopathy with Child-Pugh B or C score, including viral infection or hepatitis, alcohol abuse or cirrhosis.

• Any acute or chronic condition that may result in tissue hypoxia (e.g. heart or respiratory failure, shock).

• Bilateral hip prosthesis

• Treatment with any investigational drug or participation in a clinical trial within 30 days prior to inclusion.

• Known hypersensitivity to metformin or any of its components

• Inability or reluctance to swallow oral medications

• Persons deprived of liberty, under a measure of safeguard of justice, under guardianship or under the tutor authority

• Inability to undergo medical monitoring of the trial for geographical, social or psychological reasons.