Relapse in Previously Irradiated Prostate Bed : Stereotactic Ablative Reirradiation Potentiated by Metformin (REPAIRGETUGP16)

This is an interventional treatment trial for Prostate Cancer focused on measuring Prostate Cancer, Stereotactic Body Radiation Therapy, SBRT, Metformin, Previously Irradiated Prostate Bed, Biochemical recurrence Read More

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.