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

Institut Cancerologie de l'Ouest

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Prostate Cancer

Treatments: Radiation: Stereotactic Body Radiation Therapy (SBRT) 30 Gray (Gy); Drug: Metformin; Radiation: Stereotactic Body Radiation Therapy (SBRT) 25 Gy; Radiation: Stereotactic Body Radiation Therapy (SBRT) 36 Gy

Study type: Interventional

Funder types: Other

Identifiers

NCT04536805

ICO-2020-01

Details and patient eligibility

About

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

Full 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.

Enrollment: 44 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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44 participants in 3 patient groups

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

Experimental group

Description:

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)

Treatment:

Drug: Metformin

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

Metformin + SBRT at total dose of 36 Gy

Experimental group

Description:

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)

Treatment:

Radiation: Stereotactic Body Radiation Therapy (SBRT) 36 Gy

Drug: Metformin

Metformin + SBRT at total dose of 25 Gy

Experimental group

Description:

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)

Treatment:

Radiation: Stereotactic Body Radiation Therapy (SBRT) 25 Gy

Drug: Metformin