Reirradiation of prostate cancer using SBRT and Metformin

Relapse in Previously Irradiated Prostate Bed : a Phase I/II Study of Stereotactic Ablative Reirradiation Potentiated by Metformin

This study is testing if combining a special type of radiation therapy with Metformin can help men whose prostate cancer has come back after previous treatment.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 44 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Institut Cancerologie de l'Ouest (Academic / other)
• Locations: 12 sites (Angers and 11 other locations)
• Trial ID: NCT04536805 on ClinicalTrials.gov

What this trial studies

This phase I/II study evaluates the effectiveness of stereotactic body radiation therapy (SBRT) combined with Metformin for patients experiencing relapse in the prostate bed after prior radiation treatment. The study aims to determine the optimal dose of SBRT while monitoring treatment toxicity. Patients will receive a total radiation dose of 25 to 36 Gy over a maximum of 12 days, alongside oral Metformin treatment starting 15 days prior to radiation. Participants will be followed for five years to assess treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates include men with biochemical recurrence of prostate cancer at least two years post-radiation and hormone therapy, without pelvic lymph node or metastatic disease.

Not a fit: Patients with active pelvic lymph node or metastatic recurrence, or those with rectal invasion, may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option for patients with recurrent prostate cancer after previous radiation therapy.

How similar studies have performed: While the combination of SBRT and Metformin is a novel approach, previous studies have shown promise in using SBRT for prostate cancer treatment.

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.

Where this trial is running

Angers and 11 other locations

• Institut de Cancerologie de L'Ouest — Angers, France (Recruiting)
• CHRU de BREST - HOPITAL MORVAN — Brest, France (Recruiting)
• Societe de Recherche Oncologique Clinique 37 (Roc 37) — Chambray-lès-Tours, France (Not_yet_recruiting)
• Centre GEORGES FRANCOIS LECLERC — Dijon, France (Not_yet_recruiting)
• Clinique Victor Hugo — Le Mans, France (Not_yet_recruiting)
• Centre OSCAR LAMBRET — Lille, France (Recruiting)
• Centre LEON BERARD — Lyon, France (Recruiting)
• Centre Eugene Marquis — Rennes, France (Not_yet_recruiting)
• Centre Henri Becquerel — Rouen, France (Not_yet_recruiting)
• Institut de Cancerologie de L'Ouest — Saint-Herblain, France (Recruiting)
• ICANS - Institut de cancérologie Strasbourg Europe — Strasbourg, France (Recruiting)
• Chru Bretonneau — Tours, France (Not_yet_recruiting)

Study contacts

• Principal investigator: Valentine GUIMAS, MD — Institut de Cancérologie de l'Ouest
• Study coordinator: Valentine GUIMAS, MD

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