SAKK 08/15 - PROMET - Salvage Radiotherapy +/- Metformin for Patients With Prostate Cancer After Prostatectomy

NCT ID: NCT02945813

Last Updated: 2022-04-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-24
• Study Completion Date: 2022-02-28

Brief Summary

The main objective of the trial is to explore the efficacy of salvage radiotherapy (SRT) plus metformin compared to SRT in the endpoint of time to progression after prostatectomy failure.

Detailed Description

Although the use of salvage radiotherapy (SRT) is the only potentially curative treatment after prostatectomy failure, it has provided suboptimal results over the years. Metformin may represent an effective and inexpensive means to improve SRT outcomes with a favorable therapeutic ratio. Taken pre-clinical and retrospective clinical data together, there is a compelling rationale for conducting a RCT with SRT and metformin. Herein we propose a multicenter, randomized, open-label, proof-of-concept phase II trial with the hypothesis that the addition of metformin to SRT can delay time to progression compared to the standard-of-care SRT. The study has 1:1 randomization and stratification variables include Gleason score, PSA at SRT, surgical margin status and ADT use.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Arm A: Metformin

• Metformin - 850mg PO BID; 48 weeks
• Salvage radiotherapy SRT - 35 x 2Gy; 7 weeks

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

850mg PO BID; 48 weeks

Salvage Radiotherapy SRT

Intervention Type: RADIATION

SRT 35 x 2Gy; 7 weeks

Arm B: Salvage Radiotherapy

\- Salvage radiotherapy SRT - 35 x 2Gy; 7 weeks

Group Type: ACTIVE_COMPARATOR

Salvage Radiotherapy SRT

Intervention Type: RADIATION

SRT 35 x 2Gy; 7 weeks

Interventions

Metformin

850mg PO BID; 48 weeks

Intervention Type: DRUG

Salvage Radiotherapy SRT

SRT 35 x 2Gy; 7 weeks

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Written informed consent according to ICH/GCP regulations before registration and prior to any trial specific procedures
• Histologically confirmed adenocarcinoma of the prostate without small cell features
• Tumor stage pT2a-3b, pN0 or cN0, M0, R0-1 resection margins, according to UICC TNM 2009, Gleason score available
• Radical prostatectomy (RP) at least 12 weeks before registration
• PSA progression after RP defined as two consecutive rises with the final PSA > 0.1 ng/mL or three consecutive rises. The first value must be measured earliest 4 weeks after RP
• PSA ≤ 2 ng/mL within 14 days prior to registration
• Age ≥ 18 years at time of registration
• WHO performance status 0-1
• Adequate hepatic function within 14 days prior to registration: bilirubin ≤ 1.5 x ULN (exception if Gilbert's syndrome ≤ 3 x ULN), AST and ALT ≤ 2.5 x ULN
• Adequate renal function within 14 days prior to registration: calculated corrected creatinine clearance ≥ 60 mL/min, according to the formula of corrected Cockcroft-Gault Patient agrees not to father a child and to use effective contraceptive methods during salvage radiotherapy and until 6 months after the last fraction of radiotherapy

Exclusion Criteria

• Persistent PSA (> 0.4 ng/mL) 4 to 20 weeks after RP
• Pelvic lymph node enlargement > 0.8 cm in short axis diameter (cN positive) assessed by mpMRI within 12 weeks prior to registration, unless the enlarged lymph node is sampled and negative
• Evidence of macroscopic local recurrence assessed by mpMRI within 12 weeks prior to registration
• Palpable prostatic fossa mass suggestive of recurrence, unless an ultrasound guided biopsy is negative for malignancy
• Presence or history of prostate cancer metastases. In case of clinical suspicion (e.g. bone pain), imaging (e.g. bone scan, Choline-PET, PSMA-PET, whole body MRI) must be performed. The imaging method is at the discretion of the investigator.
• If PET/CT scan was performed, any metabolic uptake considered clinically suspicious for malignancy, unless biopsy proves to be negative.
• History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years from registration with the exception of curatively treated localized non-melanoma skin cancer
• Patients diagnosed with diabetes mellitus
• Treatment with metformin within the last 3 months prior to registration
• Prior pelvic radiotherapy
• Hormonal treatment as bilateral orchiectomy prior or following RP
• Usage of products known to affect PSA levels within 4 weeks prior to start of trial treatment
• Bilateral hip prosthesis
• Severe or active co-morbidity likely to impact on the advisability of salvage RT, e.g.:

• History of inflammatory bowel disease or any malabsorption syndrome or conditions that would interfere with enteral absorption
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
• Transmural myocardial infarction within the last 6 months
• Chronic Obstructive Pulmonary Disease (COPD) exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
• Any condition associated with increased risk of lactic acidosis (e.g. alcohol abuse, congestive heart failure NYHA III or IV
• Clinically significant history of liver disease consistent with Child-Pugh Class B or C, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Severe or uncontrolled kidney disease resulted in impaired kidney function (GFR <60ml/min)
• Any acute or chronic condition that could cause tissue hypoxia (e.g. cardiac or respiratory insufficiency, recent myocardial infarction, shock)
• Treatment with any experimental drug or participation within a clinical trial within 30 days prior to registration (exception: concurrent participation in the biobank project SAKK 63/12 is allowed)
• Any concomitant drug contraindicated for use with metformin according to the approved product information
• Known hypersensitivity to metformin/placebo or to any of its components
• Hereditary intolerance to fructose; known galactose-1-phosphate uridyl transferase deficiency, UDP galactose 4 epimerase deficiency, galactokinase deficiency, Fanconi-Bickel syndrome, congenital lactase deficiency, or glucose-galactose malabsorption (due to the lactose-containing placebo)
• Inability or unwillingness to swallow oral medication
• Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel M. Aebersold, Prof

Role: STUDY_CHAIR

Bern University Hospital - Radiation Oncology

Alan Dal Pra, MD

Role: STUDY_CHAIR

Miller School of Medicine, University of Miami

Locations

Centre Hospitalier Régional Universitaire (CHRU) Jean Minjoz

Besançon, , France

Clinique Pasteur - Centre finistérien de radiothérapie et d'oncologie

Brest, , France

Centre de lutte contre le cancer Léon Bérard

Lyon, , France

Hôpital Saint-Louis

Paris, , France

CHU de Poitiers - La Miletrie

Poitiers, , France

Institut de Cancérologie de L'Ouest René Gauducheau

Saint-Herblain, , France

Institut de Cancérologie de la Loire Lucien Neuwirth

Saint-Priest-en-Jarez, , France

Clinique Pasteur - Oncorad

Toulouse, , France

Universitätsmedizin Berlin

Berlin, , Germany

Klinikum der Universität München

München, , Germany

Universitätsklinikum Rostock

Rostock, , Germany

Universitätsklinik Tübingen

Tübingen, , Germany

Universitätsklinikum Würzburg

Würzburg, , Germany

Universitätsspital Basel

Basel, , Switzerland

EOC-Istituto Oncologico della Svizzera Italiana

Bellinzona, , Switzerland

Inselspital Bern

Bern, , Switzerland

Kantonsspital Graubuenden

Chur, , Switzerland

HFR - Hôpital cantonal

Fribourg, , Switzerland

Hôpitaux Universitaires Genève HUG

Geneva, , Switzerland

Clinique de Genolier

Genolier, , Switzerland

Spital Thurgau

Münsterlingen, , Switzerland

Kantonsspital St. Gallen

Sankt Gallen, , Switzerland

Hopital de Sion

Sion, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

Klinik Hirslanden

Zurich, , Switzerland

Stadtspital Triemli

Zurich, , Switzerland

UniversitätsSpital Zürich

Zurich, , Switzerland

Countries

France; Germany; Switzerland

Other Identifiers

2016-003599-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SAKK 08/15 - PROMET

Identifier Type: -

Identifier Source: org_study_id