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Trial record 2 of 2 for:    SAKK 08/16

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02640534
Recruitment Status : Recruiting
First Posted : December 29, 2015
Last Update Posted : December 16, 2019
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research

Tracking Information
First Submitted Date  ICMJE December 22, 2015
First Posted Date  ICMJE December 29, 2015
Last Update Posted Date December 16, 2019
Actual Study Start Date  ICMJE June 10, 2016
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 28, 2015)
Disease control (DC) [ Time Frame: at 15 months ]
The primary endpoint of the trial is disease control (DC) at 15 months.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02640534 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2017)
  • Overall response (OR) [ Time Frame: at 15 months ]
    Overall response (OR) according to modified RECIST and PCWG2 recommendations.
  • Event-free survival (EFS) [ Time Frame: at 15 months ]
    EFS is defined as the time from randomization until progression or death due to any reason.
  • Adverse events (AEs) [ Time Frame: at 15 months ]
    AEs will be assessed according to NCI CTCAE v4.0.
  • Overall survival (OS) [ Time Frame: at 15 months ]
    OS will be calculated from randomization until death due any reason.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 28, 2015)
  • Overall response (OR) [ Time Frame: at 15 months ]
    Overall response (OR) according to PCWG2 recommendations
  • Event-free survival (EFS) [ Time Frame: at 15 months. ]
  • Adverse events (AEs) [ Time Frame: at 15 months. ]
  • Overall survival (OS) [ Time Frame: at 15 months. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Investigation of Metformin in Patients With Castration Resistant Prostate Cancer in Combination With Enzalutamide vs. Enzalutamide Alone
Official Title  ICMJE 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
Brief 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. The half of the patients will receive the experimental treatment combination, enzalutamide and metformin, while the other half will receive enzalutamide alone.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cancer of the Prostate
  • Prostate Cancer
Intervention  ICMJE
  • Drug: Enzalutamide
    Enzalutamide 160 mg od until disease progression
  • Drug: Metformin
    850 mg bid until disease progression
Study Arms  ICMJE
  • Experimental: Enzalutamide + Metformin
    Enzalutamide 160 mg od + metformin 850 mg bid until disease progression
    Interventions:
    • Drug: Enzalutamide
    • Drug: Metformin
  • Active Comparator: Enzalutamide
    Enzalutamide 160 mg od until disease progression
    Intervention: Drug: Enzalutamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 28, 2015)
168
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2028
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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)
  • 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.

Exclusion Criteria:

  • 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,
    • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Eloise Kremer, PhD +41 31 389 91 91 trials@sakk.ch
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02640534
Other Study ID Numbers  ICMJE SAKK 08/14 - IMPROVE
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Swiss Group for Clinical Cancer Research
Study Sponsor  ICMJE Swiss Group for Clinical Cancer Research
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Christian Rothermundt, MD Cantonal Hospital of St. Gallen
PRS Account Swiss Group for Clinical Cancer Research
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP