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

NCT04536805 | Recruiting Phase 1 DMC

• 1 other identifier: ICO-2020-01
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 12

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

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Stereotactic Body Radiation Therapy; SBRT; Metformin; Previously Irradiated Prostate Bed; Biochemical recurrence

Outcome Measures

Primary Outcomes (2)

• For phase 1:. Select the recommended dose for SBRT (either 5 x 6 Gy, 6 x 6 Gy, or 5 x 5 Gy), in combination with Metformin

  SBRT toxicity will be reported during the 12 weeks following the initiation of SBRT.

  12 weeks

• For phase 2: estimate the efficacy of re-irradiation SBRT in combination with Metformin in terms of biochemical relapse-free survival rate.

  PSA levels will be assessed every 3 months within 3 years after SBRT.

  3 years

Secondary Outcomes (7)

• Estimate the efficacy of re-irradiation SBRT in combination with Metformin in terms of biochemical relapse-free survival and biochemical response

  5 years

• Estimation of the efficacy of SBRT re-irradiation in combination with Metformin in terms of progression-free survival and overall survival

  5 years

• Evaluation of acute and late genitourinary and gastrointestinal toxicities of the SBRT re-irradiation

  5 years

• Evaluation of Quality of life after SBRT re-irradiation in combination with Metformin

  5 years

• Evaluation of Quality of life after SBRT re-irradiation in combination with Metformin

  5 years

Study Arms (3)

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

EXPERIMENTAL

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)

Drug: Metformin; Radiation: Stereotactic Body Radiation Therapy (SBRT) 30 Gray (Gy)

Metformin + SBRT at total dose of 36 Gy

EXPERIMENTAL

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)

Drug: Metformin; Radiation: Stereotactic Body Radiation Therapy (SBRT) 36 Gy

Metformin + SBRT at total dose of 25 Gy

EXPERIMENTAL

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)

Drug: Metformin; Radiation: Stereotactic Body Radiation Therapy (SBRT) 25 Gy

Interventions

Metformin DRUG

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

Metformin + SBRT at total dose of 25 Gy; Metformin + SBRT at total dose of 30 Gray (Gy); Metformin + SBRT at total dose of 36 Gy

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

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

Also known as: SBRT

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

Stereotactic Body Radiation Therapy (SBRT) 36 Gy RADIATION

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

Also known as: SBRT

Metformin + SBRT at total dose of 36 Gy

Stereotactic Body Radiation Therapy (SBRT) 25 Gy RADIATION

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

Metformin + SBRT at total dose of 25 Gy

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Men
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Severe comorbidity that may affect treatment, for example :
• Unstable angina, myocardial infarction and/or congestive heart failure requiring hospitalization within the last 6 months
• Myocardial infarction in the last 6 months.
• 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

Sponsors & Collaborators

• Institut Cancerologie de l'Ouest: lead

Study Sites (12)

Institut de Cancerologie de L'Ouest

Angers, 49055, France

RECRUITING

CHRU de BREST - HOPITAL MORVAN

Brest, 29200, France

RECRUITING

Societe de Recherche Oncologique Clinique 37 (Roc 37)

Chambray-lès-Tours, 37170, France

NOT YET RECRUITING

Centre GEORGES FRANCOIS LECLERC

Dijon, 21079, France

NOT YET RECRUITING

Clinique Victor Hugo

Le Mans, 72100, France

NOT YET RECRUITING

Centre OSCAR LAMBRET

Lille, 59020, France

RECRUITING

Centre LEON BERARD

Lyon, 69373, France

RECRUITING

Centre Eugene Marquis

Rennes, 35042, France

NOT YET RECRUITING

Centre Henri Becquerel

Rouen, 76038, France

NOT YET RECRUITING

Institut de Cancerologie de L'Ouest

Saint-Herblain, 44805, France

RECRUITING

ICANS - Institut de cancérologie Strasbourg Europe

Strasbourg, 67200, France

RECRUITING

Chru Bretonneau

Tours, 37044, France

NOT YET RECRUITING

Related Publications (1)

• 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.

  PMID: 40707156 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Metformin; Radiosurgery

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Valentine GUIMAS, MD

  Institut de Cancérologie de l'Ouest

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Valentine GUIMAS, MD

CONTACT

+33 (0)240679916; valentine.guimas@ico.unicancer.fr

Nadia ALLAM, PhD

CONTACT

+33 2 40 67 98 26; nadia.allam@ico.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2020
• First Posted: September 3, 2020
• Study Start: November 17, 2020
• Primary Completion (Estimated): November 1, 2031
• Study Completion (Estimated): November 1, 2031
• Last Updated: December 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 6 months and ending 3 years following article publication
• Access Criteria: Researchers who provide a methodologically sound proposal not overlapping with any planned secondary publications from the research team will be able to access the IPD. To achieve aims in the approved proposal. Proposals should be directed to Chief Investigator who will discuss such requested with the Department of Clinical Research and Innovation (DRCI): Valentine.guimas@ico.unicancer.fr. To gain access, data requesters will need to sign a data access agreement. Data will be available for 3 years at Institut de Cancérologie de l'Ouest.

Locations

FR (12)