Clinical trial NCT04536805: Relapse in Previously Irradiated Prostate Bed : Stereotactic Ablative Reirradiation Potentiated by Metformin
Official title: Relapse in Previously Irradiated Prostate Bed : a Phase I/II Study of Stereotactic Ablative Reirradiation Potentiated by Metformin
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Keywords: Prostate Cancer
Stereotactic Body Radiation Therapy
SBRT
Metformin
Previously Irradiated Prostate Bed
Biochemical recurrence
Lead sponsor: Institut Cancerologie de l'Ouest
Sponsor class: OTHER
First posted: 2020-09-03
Enrollment: 44
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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
timeFrame: 12 weeks
measure: For phase 2: estimate the efficacy of re-irradiation SBRT in combination with Metformin in terms of biochemical relapse-free survival rate.
timeFrame: 3 years
Secondary outcomes:
measure: Estimate the efficacy of re-irradiation SBRT in combination with Metformin in terms of biochemical relapse-free survival and biochemical response
timeFrame: 5 years
measure: Estimation of the efficacy of SBRT re-irradiation in combination with Metformin in terms of progression-free survival and overall survival
timeFrame: 5 years
measure: Evaluation of acute and late genitourinary and gastrointestinal toxicities of the SBRT re-irradiation
timeFrame: 5 years
measure: Evaluation of Quality of life after SBRT re-irradiation in combination with Metformin
timeFrame: 5 years
measure: Evaluation of Quality of life after SBRT re-irradiation in combination with Metformin
timeFrame: 5 years
measure: Evaluation of urinary symptoms
timeFrame: 5 years
measure: Evaluation of erectile function
timeFrame: 5 years
Other outcomes:
Locations:
city: Angers
country: France
facility: Institut de Cancerologie de L'Ouest
city: Brest
country: France
facility: CHRU de BREST - HOPITAL MORVAN
city: Chambray-lès-Tours
country: France
facility: Societe de Recherche Oncologique Clinique 37 (Roc 37)
city: Dijon
country: France
facility: Centre GEORGES FRANCOIS LECLERC
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Lille
country: France
facility: Centre OSCAR LAMBRET
city: Lyon
country: France
facility: Centre LEON BERARD
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Herblain
country: France
facility: Institut de Cancerologie de L'Ouest
city: Strasbourg
country: France
facility: ICANS - Institut de cancérologie Strasbourg Europe
city: Tours
country: France
facility: Chru Bretonneau
Study officials:
affiliation: Institut de Cancérologie de l'Ouest
name: Valentine GUIMAS, MD
role: PRINCIPAL_INVESTIGATOR
References: