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

NCT ID: NCT04536805

Last Updated: 2025-12-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-17
• Study Completion Date: 2031-11-30

Brief 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

Detailed Description

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Metformin + SBRT at total dose of 30 Gray (Gy)

Metformin: 850 mg per day (day -15 to day 0) 1700 mg per day (day 1 to day 75)

Stereotactic Body Radiation Therapy (SBRT): Dose escalation 5 x 6 Gy, (day 0 to day 10)

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Metformin: 850 mg per day (day -15 to day 0) 1700 mg per day (day 1 to day 75)

Stereotactic Body Radiation Therapy (SBRT) 30 Gray (Gy)

Intervention Type: RADIATION

Stereotactic Body Radiation Therapy (SBRT): Dose escalation 5 x 6 Gy day 0 to day 10

Metformin + SBRT at total dose of 36 Gy

Metformin: 850 mg per day (day -15 to day 0) 1700 mg per day (day 1 to day 75)

Stereotactic Body Radiation Therapy (SBRT): Dose escalation 6 x 6 Gy (day 0 to day 12)

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Metformin: 850 mg per day (day -15 to day 0) 1700 mg per day (day 1 to day 75)

Stereotactic Body Radiation Therapy (SBRT) 36 Gy

Intervention Type: RADIATION

Stereotactic Body Radiation Therapy (SBRT): Dose escalation 6 x 6 Gy day 0 to day 12

Metformin + SBRT at total dose of 25 Gy

Metformin: 850 mg per day (day -15 to day 0) 1700 mg per day (day 1 to day 75)

Stereotactic Body Radiation Therapy (SBRT): Dose escalation 5 x 5 Gy (day 0 to day 10)

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Metformin: 850 mg per day (day -15 to day 0) 1700 mg per day (day 1 to day 75)

Stereotactic Body Radiation Therapy (SBRT) 25 Gy

Intervention Type: RADIATION

Stereotactic Body Radiation Therapy (SBRT): Dose escalation 5x 5 Gy day 0 to day 10

Interventions

Metformin

Metformin: 850 mg per day (day -15 to day 0) 1700 mg per day (day 1 to day 75)

Intervention Type: DRUG

Stereotactic Body Radiation Therapy (SBRT) 30 Gray (Gy)

Stereotactic Body Radiation Therapy (SBRT): Dose escalation 5 x 6 Gy day 0 to day 10

Intervention Type: RADIATION

Stereotactic Body Radiation Therapy (SBRT) 36 Gy

Stereotactic Body Radiation Therapy (SBRT): Dose escalation 6 x 6 Gy day 0 to day 12

Intervention Type: RADIATION

Stereotactic Body Radiation Therapy (SBRT) 25 Gy

Stereotactic Body Radiation Therapy (SBRT): Dose escalation 5x 5 Gy day 0 to day 10

Intervention Type: RADIATION

Other Intervention Names

SBRT; SBRT

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Institut Cancerologie de l'Ouest

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Valentine GUIMAS, MD

Role: PRINCIPAL_INVESTIGATOR

Institut de Cancérologie de l'Ouest

Locations

Institut de Cancerologie de L'Ouest

Angers, , France

Site Status: RECRUITING

CHRU de BREST - HOPITAL MORVAN

Brest, , France

Site Status: RECRUITING

Societe de Recherche Oncologique Clinique 37 (Roc 37)

Chambray-lès-Tours, , France

Site Status: NOT_YET_RECRUITING

Centre GEORGES FRANCOIS LECLERC

Dijon, , France

Site Status: NOT_YET_RECRUITING

Clinique Victor Hugo

Le Mans, , France

Site Status: NOT_YET_RECRUITING

Centre OSCAR LAMBRET

Lille, , France

Site Status: RECRUITING

Centre LEON BERARD

Lyon, , France

Site Status: RECRUITING

Centre Eugene Marquis

Rennes, , France

Site Status: NOT_YET_RECRUITING

Centre Henri Becquerel

Rouen, , France

Site Status: NOT_YET_RECRUITING

Institut de Cancerologie de L'Ouest

Saint-Herblain, , France

Site Status: RECRUITING

ICANS - Institut de cancérologie Strasbourg Europe

Strasbourg, , France

Site Status: RECRUITING

Chru Bretonneau

Tours, , France

Site Status: NOT_YET_RECRUITING

Countries

France

Central Contacts

Valentine GUIMAS, MD

Role: CONTACT

valentine.guimas@ico.unicancer.fr

+33 (0)240679916

Nadia ALLAM, PhD

Role: CONTACT

nadia.allam@ico.unicancer.fr

+33 2 40 67 98 26

Facility Contacts

Nathalie MESGOUEZ-NEBOUT, MD

Role: primary

nathalie.mesgouez-nebout@ico.unicancer.fr

+33(0)241352912

Ulrike SCHICK, MD

Role: primary

ulrike.schick@chu-brest.fr

+33(0)2 98 22 33 33

Thomas BOISSERIE, MD

Role: primary

t.boisserie@cort37.fr

Magali QUIVRIN, MD

Role: primary

mquivrin@cgfl.fr

+33(0)3 80 73 75 18

Amandine RUFFIER LOUBIERE, MD

Role: primary

essaisruffier@ilcgroupe.fr

David PASQUIER, MD

Role: primary

d-pasquier@o-lambret.fr

+33(0)320295911

Pascal POMMIER, MD

Role: primary

pascal.pommier@lyon.unicancer.fr

+33(0)4 78 78 28 28

Renaud DE CREVOISIER, MD

Role: primary

r.de-crevoisier@rennes.unicancer.fr

+33(0)2 99 63 91 78

Maximilien ROGE, MD

Role: primary

maximilien.roge@chb.unicancer.fr

Valentine GUIMAS, MD

Role: primary

valentine.guimas@ico.unicancer.fr

+33 (0)240679916

Jean-Baptiste Jean-Baptiste, MD

Role: primary

jb.clavier@icans.eu

Gilles CALAIS, MD

Role: primary

gilles.calais@univ-tours.fr

+33(0)2 47 47 82 65

References

Joly A, Blanc Lapierre A, Rio E, Vaugier L, Supiot S, Guimas V. REPAIR_GETUG P16 relapse in previously irradiated prostate bed: a phase I/II study of stereotactic ablative reirradiation potentiated by a metformine study protocol. BMJ Open. 2025 Jul 24;15(7):e100031. doi: 10.1136/bmjopen-2025-100031.

Reference Type: DERIVED

PMID: 40707156 (View on PubMed)

Other Identifiers

ICO-2020-01

Identifier Type: -

Identifier Source: org_study_id