relapse in previously irradiated prostate bed : stereotactic ablative reirradiation potentiated by metformin

Conditions: Prostate Cancer

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

the purpose of this escalation study is, first to select the recommended dose of re-irradiation sbrt in combination with metformin (based on treatment toxicity monitoring) and then to estimate the efficacy of re-irradiation sbrt in combination with metformin. five or six fractions, at a level of 5 or 6 gray (gy) per session (either 5 x 6 gy, 6 x 6 gy, or 5 x 5 gy), will be delivered over a maximum of 12 days (from day 1 to day 10 or 12) to provide a total dose of 25 to 36 gy. patient receive oral metformin treatment from day -15 and day 75. patient will be followed for 5 years: patients visits will be planned at week 2; 4; 8; 12; and month m6; m9; m12; m18; m24; m36; 4 years and 5 years.

Eligibility 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 to the prostate lodge and 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 at least 2 successive assays) and radiological (lesion visible on mri and/or choline pet and/or prostate-specific membrane antigen (psma) pet). * recurrence without rectal invasion * 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 * low risk, intermediate risk and high risk with a single risk factor * 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 * rectal surgery history * patient treated for diabetes * 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.

Keywords: prostate cancer stereotactic body radiation therapy sbrt metformin previously irradiated prostate bed biochemical recurrence