AzTrials
AzTrials

Prostate CancerPhase 2NCT02945813

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

A Phase 2 study testing Metformin and Salvage Radiotherapy SRT in people with Prostate Cancer, run by Swiss Cancer Institute at 27 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years, men only
Conditions the study is for
Prostate Cancer
What is being tested?
Metformin and Salvage Radiotherapy SRT
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
112 participants
Where
27 sitesin 3 countries
Study dates
24 Oct 2017to 28 Feb 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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

Who cannot join

  • 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.
Show all 29Show fewer
  • 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

Trial locations and contacts

27 sites in 3 countries.

27 sites in 3 countries

Switzerland14 sites

  • Universitätsspital Basel

    Basel, 4031

  • EOC-Istituto Oncologico della Svizzera Italiana

    Bellinzona, 6500

  • Inselspital Bern

    Bern, 3010

  • Kantonsspital Graubuenden

    Chur, 7000

  • HFR - Hôpital cantonal

    Fribourg, 1708

  • Hôpitaux Universitaires Genève HUG

    Geneva, 1211

  • Clinique de Genolier

    Genolier, 1272

  • Spital Thurgau

    Münsterlingen, CH-8596

  • Kantonsspital St. Gallen

    Sankt Gallen, 9007

  • Hopital de Sion

    Sion, 1951

  • Kantonsspital Winterthur

    Winterthur, 8401

  • Klinik Hirslanden

    Zurich, 8032

  • Stadtspital Triemli

    Zurich, 8063

  • UniversitätsSpital Zürich

    Zurich, 8091

Other trials in Switzerland

France8 sites

  • Centre Hospitalier Régional Universitaire (CHRU) Jean Minjoz

    Besançon, 25030

  • Clinique Pasteur - Centre finistérien de radiothérapie et d'oncologie

    Brest, 29220

  • Centre de lutte contre le cancer Léon Bérard

    Lyon, 69008

  • Hôpital Saint-Louis

    Paris, 75010

  • CHU de Poitiers - La Miletrie

    Poitiers, 86021

  • Institut de Cancérologie de L'Ouest René Gauducheau

    Saint-Herblain, 44800

  • Institut de Cancérologie de la Loire Lucien Neuwirth

    Saint-Priest-en-Jarez, 42270

  • Clinique Pasteur - Oncorad

    Toulouse, 31076

Other trials in France

Germany5 sites

  • Universitätsmedizin Berlin

    Berlin, 13353

  • Klinikum der Universität München

    München, 81377

  • Universitätsklinikum Rostock

    Rostock, 18059

  • Universitätsklinik Tübingen

    Tübingen, 72076

  • Universitätsklinikum Würzburg

    Würzburg, 97080

Other trials in Germany

About this study

Official title: SAKK 08/15 - PROMET - Multicenter, Randomized Phase II Trial of Salvage Radiotherapy +/- Metformin for Patients With Prostate Cancer After Prostatectomy

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.

Read the 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
Being tested
Metformin, Salvage Radiotherapy SRT
Keywords
Prostate Cancer, Prostate Cancer after Prostatectomy, Phase II Trial, Salvage Radiotherapy, Metformin
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

    850mg PO BID; 48 weeks

  • Salvage Radiotherapy SRTRadiation

    SRT 35 x 2Gy; 7 weeks

Study groups in NCT02945813
Study groupRoleWhat they receive
Arm A: MetforminExperimental* Metformin - 850mg PO BID; 48 weeks * Salvage radiotherapy SRT - 35 x 2Gy; 7 weeks
Receives: Drug: Metformin; Radiation: Salvage Radiotherapy SRT
Arm B: Salvage RadiotherapyActive comparator- Salvage radiotherapy SRT - 35 x 2Gy; 7 weeks
Receives: Radiation: Salvage Radiotherapy SRT

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: within 18 months after randomization

Secondary outcomes (8)

  1. Progression free survival (PFS)

    PFS is defined as time from randomization until one of the following events, whichever comes first:

    • Biochemical progression
    • Clinical progression
    • Death from any cause

    Measured: within 18 months after randomization

  2. Undetectable Prostate Specific Antigen (PSA) under normal testosterone levels

    Undetectable PSA is defined as a serum PSA value of ≤0.05 ng/mL for at least two consecutive measurements after the last radiotherapy fraction and up to 18 months thereafter. To count as undetectable PSA under normal testosterone levels, the testosterone level has to be ≥50 ng/dL (i.e. a non-castrate testosterone level).

    Measured: up to 18 months after last radiotherapy fraction

  3. 50% PSA response

    50% PSA response is defined as a ≥50% PSA decline after radiotherapy compared to the serum PSA level at randomization up to 18 months after last radiotherapy fraction.

    Measured: at randomization up to 18 months after last radiotherapy fraction.

  4. Clinical progression-free survival

    Clinical progression-free survival will be calculated as the time from randomization until clinical progression or death due to any cause.

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

  5. Time to further anti-cancer systemic therapy

    Time to further anti-cancer systemic therapy (e.g. hormonal treatment) is defined as the time from randomization to the start of any type of salvage systemic treatment.

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

  6. Prostate cancer-specific survival (PCSS)

    Prostate cancer-specific survival will be calculated as the time from randomization to the date of death due to prostate cancer.

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

  7. Overall survival (OS)

    Overall survival will be calculated as the time from randomization to the date of death from any cause.

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

  8. Adverse Events (AE)

    AEs will be assessed according to NCI CTCAE v4.03.

    Measured: until 56 weeks (specific RT-related AEs : until 10 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2016 (estimated)
  2. Study start24 Oct 2017
  3. Primary completion28 Feb 2022
  4. Study completion28 Feb 2022

Why it stopped: Trial was prematurely closed for accrual by the SAKK Board and the follow-up period shortened to one year after last RT fraction of the last patient

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
112 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02945813
Sponsor's protocol ID
SAKK 08/15 - PROMET
Other IDs
2016-003599-39, 2016
Status last verified
Apr 2022
First submitted
25 Oct 2016
Last updated
14 Apr 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Metformin and Salvage Radiotherapy SRT in people with Prostate Cancer, run by Swiss Cancer Institute at 27 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in Switzerland, France, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Trial was prematurely closed for accrual by the SAKK Board and the follow-up period shortened to one year after last RT fraction of the last patient). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to progression (TTP) (time frame: within 18 months after randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02945813.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in