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

NCT02945813 | Terminated Phase 2 DMC

• 2 other identifiers: SAKK 08/15 - PROMET2016-003599-39
• Study Type: interventional
• Target: 112
• Locations: 3 countries
• Sites: 27

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.

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Prostate Cancer after Prostatectomy; Phase II Trial; Salvage Radiotherapy; Metformin

Outcome Measures

Primary Outcomes (1)

• Time to progression (TTP)

  The primary endpoint of the trial is time to progression (TTP), defined as time from randomization until one of the following events, whichever comes first: * Biochemical progression * Clinical progression * Death due to clinical progression

  within 18 months after randomization

Secondary Outcomes (8)

• Progression free survival (PFS)

  within 18 months after randomization

• Undetectable Prostate Specific Antigen (PSA) under normal testosterone levels

  up to 18 months after last radiotherapy fraction

• 50% PSA response

  at randomization up to 18 months after last radiotherapy fraction.

• Clinical progression-free survival

  week 64 then every 6 months for the first year and every 12 months thereafter up to 10 years from last RT fraction.

• Time to further anti-cancer systemic therapy

  week 64 then every 6 months for the first year and every 12 months thereafter up to 10 years from last RT fraction.

Study Arms (2)

Arm A: Metformin

EXPERIMENTAL

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

Drug: Metformin; Radiation: Salvage Radiotherapy SRT

Arm B: Salvage Radiotherapy

ACTIVE COMPARATOR

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

Radiation: Salvage Radiotherapy SRT

Interventions

Metformin DRUG

850mg PO BID; 48 weeks

Arm A: Metformin

Salvage Radiotherapy SRT RADIATION

SRT 35 x 2Gy; 7 weeks

Arm A: Metformin; Arm B: Salvage Radiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (27)

Centre Hospitalier Régional Universitaire (CHRU) Jean Minjoz

Besançon, 25030, France

Location

Clinique Pasteur - Centre finistérien de radiothérapie et d'oncologie

Brest, 29220, France

Location

Centre de lutte contre le cancer Léon Bérard

Lyon, 69008, France

Location

Hôpital Saint-Louis

Paris, 75010, France

Location

CHU de Poitiers - La Miletrie

Poitiers, 86021, France

Location

Institut de Cancérologie de L'Ouest René Gauducheau

Saint-Herblain, 44800, France

Location

Institut de Cancérologie de la Loire Lucien Neuwirth

Saint-Priest-en-Jarez, 42270, France

Location

Clinique Pasteur - Oncorad

Toulouse, 31076, France

Location

Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Klinikum der Universität München

München, 81377, Germany

Location

Universitätsklinikum Rostock

Rostock, 18059, Germany

Location

Universitätsklinik Tübingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

Universitätsspital Basel

Basel, 4031, Switzerland

Location

EOC-Istituto Oncologico della Svizzera Italiana

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

Kantonsspital Graubuenden

Chur, 7000, Switzerland

Location

HFR - Hôpital cantonal

Fribourg, 1708, Switzerland

Location

Hôpitaux Universitaires Genève HUG

Geneva, 1211, Switzerland

Location

Clinique de Genolier

Genolier, 1272, Switzerland

Location

Spital Thurgau

Münsterlingen, CH-8596, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Hopital de Sion

Sion, 1951, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

Klinik Hirslanden

Zurich, 8032, Switzerland

Location

Stadtspital Triemli

Zurich, 8063, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Metformin

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

Study Officials

• Daniel M. Aebersold, Prof

  Bern University Hospital - Radiation Oncology

  STUDY CHAIR

• Alan Dal Pra, MD

  Miller School of Medicine, University of Miami

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2016
• First Posted: October 26, 2016
• Study Start: October 24, 2017
• Primary Completion: February 28, 2022
• Study Completion: February 28, 2022
• Last Updated: April 14, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (5); CH (14); FR (8)