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Cancer of the ProstatePhase 2NCT02640534

Investigation of Metformin in Patients With Castration Resistant Prostate Cancer in Combination With Enzalutamide vs. Enzalutamide Alone

A Phase 2 study testing Enzalutamide and Metformin in people with Cancer of the Prostate and Prostate Cancer, run by Swiss Cancer Institute at 16 sites in Switzerland.

Terminated

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

Official record
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Trial summary

The purpose of this trial is to test if the combination of enzalutamide and metformin in patients with castration resistant prostate cancer CRPC progressing on androgen deprivation therapy ADT is more effective compared to enzalutamide alone. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Cancer of the Prostate, Prostate Cancer
What is being tested?
Enzalutamide and Metformin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
169 participants
Where
16 sitesSwitzerland
Study dates
10 Jun 2016to 16 Mar 2023
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 years and older
  • 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-related investigations
  • Histologically or cytological confirmed adenocarcinoma of the prostate without small cell carcinoma or small cell components
  • Asymptomatic or minimally symptomatic patients in relation to disease
  • Metastatic adenocarcinoma of the prostate documented by imaging (CT/MRI and/or bone scan)
  • Ongoing androgen deprivation therapy with Gonadotropin-releasing hormone GnRH analogues or bilateral orchiectomy (i.e. surgical or medical castration)
  • Total testosterone levels ≤ 1.7 nmol/L (corresponding to ≤ 50 ng/dL)
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  • Tumor progression at the time of registration, defined as per protocol.
  • Completed baseline QoL and pain questionnaires
  • Male patients ≥ 18 years
  • WHO performance status 0-2
  • Adequate hematologic values: hemoglobin ≥ 90 g/L, neutrophils ≥ 1.0 x 109/L, platelets ≥ 75 x 109/L
  • Adequate hepatic function: ALT and AST ≤ 2.5 x ULN, bilirubin ≤ 1.5 x ULN (exception if Gilbert's syndrome ≤ 2.5 x ULN)
  • Adequate renal function: calculated creatinine clearance ≥ 50 mL/min, according to the formula of Cockcroft-Gault
  • Patient is able to swallow the trial drugs and comply with trial requirements
  • Patient agrees not to father a child during participation in the trial and during 3 months thereafter
  • Patient agrees to participate to the mandatory translational research part of the trial with exception of Pyruvate dehydrogenase sub-study.

Who cannot join

  • Known or suspected Central nervous system CNS metastases or active leptomeningeal disease
  • Previous malignancy within 2 years prior to registration, with the exception of localized non-melanoma skin cancer and Ta and Tis bladder cancer
  • Prior treatment for prostate cancer with
  • novel endocrine agents (including abiraterone acetate, enzalutamide, TAK-700, TAK-683, TAK-448, VT464, darolutamide, apalutamide),
  • radioisotopes,
  • TKI and other small molecules,
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  • immunotherapy,
  • chemotherapy (with the exception of docetaxel chemotherapy in hormone sensitive prostate cancer)
  • Treatment with experimental drugs or treatment within a clinical trial within 30 days prior to registration (except the clinical trial SAKK 96/12, PEACE-4 and/or the biobank project SAKK 63/12)
  • Clinically significant cardiovascular disease including:
  • Myocardial infarction within 6 months prior to registration,
  • Uncontrolled angina within 3 months prior to registration,
  • Congestive heart failure NYHA class III or IV,
  • QTc interval > 480 ms,
  • History of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes),
  • History of Mobitz II second or third degree heart block without a permanent pacemaker in place,
  • Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg OR diastolic blood pressure > 105 mmHg
  • Severe concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment (e.g. uncontrolled or acute severe infection, advanced chronic obstructive pulmonary disease, heart failure)
  • Known history of HIV, hepatitis B, hepatitis C
  • Major surgery within 4 weeks prior to registration
  • Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within 3 months prior to registration)
  • Treatment with metformin within the last 6 months prior to registration
  • Patients on pharmacotherapy for diabetes mellitus
  • History of diabetic ketoacidosis, diabetic coma and pre-coma
  • Known history of seizures or any conditions that may predispose to seizure. History of loss of consciousness or transient ischemic attack within 12 months prior to registration
  • Concurrent anticoagulation with rivaroxaban or warfarin
  • Known hypersensitivity to the IMPs or hypersensitivity to any of their components
  • Any concomitant drugs contraindicated for use with the IMPs according to the Swissmedic approved product information
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the trial protocol and follow-up.

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

Switzerland16 sites

  • Kantonsspital Aarau

    Aarau, 5001

  • Universitaetsspital Basel

    Basel, 4031

  • Istituto Oncologico della Svizzera Italiana (IOSI)

    Bellinzona, 6500

  • Kantonsspital Graubuenden

    Chur, 7000

  • Spital Thurgau AG

    Frauenfeld, CH-8500

  • Hôpitaux Universitaires de Genève

    Geneva, 1211

  • CCAC Lausanne

    Lausanne, 1004

  • Luzerner Kantonsspital

    Lucerne, 6000

  • Hôpital du Valais

    Martigny-Ville, 1920

  • Kantonsspital Olten

    Olten, CH-4600

  • Kantonsspital St. Gallen

    Sankt Gallen, 9007

  • Hôpital du Valais

    Sion, 1951

  • Bürgerspital Solothurn

    Solothurn, CH-4500

  • Kantonsspital Winterthur

    Winterthur, 8401

  • Stadtspital Triemli

    Zurich, 8063

  • UniversitätsSpital Zürich

    Zurich, 8091

Other trials in Switzerland

About this study

Official title: Investigation of Metformin in Patients With Castration Resistant Prostate Cancer in Combination With Enzalutamide vs. Enzalutamide Alone (IMPROVE TRIAL): A Randomized, Open Label, Phase II Trial

The purpose of this trial is to test if the combination of enzalutamide and metformin in patients with castration resistant prostate cancer CRPC progressing on androgen deprivation therapy ADT is more effective compared to enzalutamide alone. The half of the patients will receive the experimental treatment combination, enzalutamide and metformin, while the other half will receive enzalutamide alone.

Read the detailed description

One in seven men will be diagnosed with cancer of the prostate during his lifetime . Accordingly, prostate cancer (PC) is the most common cancer amongst men in the western world and worldwide. PC ranks second in cancer incidence and sixth in cancer mortality in men. The current standard of care for patients with metastatic castration resistant prostate cancer (mCRPC) and disease progression is either treatment with abiraterone acetate and prednisone in asymptomatic or mildly symptomatic patients without visceral metastases, or treatment with docetaxel in more symptomatic patients and in the presence of visceral metastases.

Rothemundt et al. previously demonstrated favorable effects of metformin in a phase II trial: it yields objective Prostate specific antigen PSA responses and may induce disease stabilization and improve metabolic endpoints in patients with CRPC. Therefore addition of metformin to enzalutamide might have positive impact on tumor progression, on body composition, and insulin sensitivity.

Being tested
Enzalutamide, Metformin
Keywords
Prostate cancer, Cancer of the prostate, Metformin, Enzalutamide, Xtandi, castration resistant prostate cancer, phase II, Androgen deprivation therapy
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • EnzalutamideDrug

    Enzalutamide 160 mg od until disease progression

  • MetforminDrug

    850 mg bid until disease progression

Study groups in NCT02640534
Study groupRoleWhat they receive
Enzalutamide + MetforminExperimentalEnzalutamide 160 mg od + metformin 850 mg bid until disease progression
Receives: Drug: Enzalutamide; Drug: Metformin
EnzalutamideActive comparatorEnzalutamide 160 mg od until disease progression
Receives: Drug: Enzalutamide

What is being measured

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

  1. Disease control (DC)

    The primary endpoint of the trial is disease control (DC) at 15 months.

    Measured: at 15 months

Secondary outcomes (4)

  1. Overall response (OR)

    Overall response (OR) according to modified RECIST and PCWG2 recommendations.

    Measured: at 15 months

  2. Event-free survival (EFS)

    EFS is defined as the time from randomization until progression or death due to any reason.

    Measured: at 15 months

  3. Adverse events (AEs)

    AEs will be assessed according to NCI CTCAE v4.0.

    Measured: at 15 months

  4. Overall survival (OS)

    OS will be calculated from randomization until death due any reason.

    Measured: at 15 months

Timeline

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

  1. First posted29 Dec 2015 (estimated)
  2. Study start10 Jun 2016
  3. Primary completion1 Jul 2022
  4. Study completion16 Mar 2023

Why it stopped: The decision is based on the fact that with the current follow up of around 10 years, the relevant secondary endpoints can adequately be addressed according to protocol. The addition of follow up data will not significantly impact these results.

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
None (open label)
Enrolment
169 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02640534
Sponsor's protocol ID
SAKK 08/14 - IMPROVE
Status last verified
Jun 2023
First submitted
22 Dec 2015
Last updated
27 Jun 2023
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Enzalutamide and Metformin in people with Cancer of the Prostate and Prostate Cancer, run by Swiss Cancer Institute at 16 sites in Switzerland.

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 16 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 27 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Switzerland. 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: The decision is based on the fact that with the current follow up of around 10 years, the relevant secondary endpoints can adequately be addressed according to protocol. The addition of follow up data will not significantly impact these results.). 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?

Disease control (DC) (time frame: at 15 months). 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 NCT02640534.

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 27 Jun 2023.

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