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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

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ClinicalTrials.gov Identifier: NCT02640534
Recruitment Status : Recruiting
First Posted : December 29, 2015
Last Update Posted : January 11, 2019
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research

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.

Condition or disease Intervention/treatment Phase
Cancer of the Prostate Prostate Cancer Drug: Enzalutamide Drug: Metformin Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 168 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 24, 2016
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : June 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Enzalutamide + Metformin
Enzalutamide 160 mg od + metformin 850 mg bid until disease progression
Drug: Enzalutamide
Enzalutamide 160 mg od until disease progression

Drug: Metformin
850 mg bid until disease progression

Active Comparator: Enzalutamide
Enzalutamide 160 mg od until disease progression
Drug: Enzalutamide
Enzalutamide 160 mg od until disease progression




Primary Outcome Measures :
  1. Disease control (DC) [ Time Frame: at 15 months ]
    The primary endpoint of the trial is disease control (DC) at 15 months.


Secondary Outcome Measures :
  1. Overall response (OR) [ Time Frame: at 15 months ]
    Overall response (OR) according to modified RECIST and PCWG2 recommendations.

  2. 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.

  3. Adverse events (AEs) [ Time Frame: at 15 months ]
    AEs will be assessed according to NCI CTCAE v4.0.

  4. Overall survival (OS) [ Time Frame: at 15 months ]
    OS will be calculated from randomization until death due any reason.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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, ODM201, ARN509),
    • 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02640534


Contacts
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Contact: Martina Schneider +41 31 389 91 91 trials@sakk.ch

Locations
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Switzerland
Kantonsspital Aarau Recruiting
Aarau, Switzerland, 5001
Contact: Tobias Wehrhahn, Dr. med.    +41 62 838 60 50    tobias.wehrhahn@ksa.ch   
Principal Investigator: Tobias Wehrhahn, Dr. med.         
Universitaetsspital Basel Recruiting
Basel, Switzerland, 4031
Contact: Sacha Rothschild, MD    +41 61 265 25 25    sacha.rothschild@usb.ch   
Principal Investigator: Sacha Rothschild, MD         
Istituto Oncologico della Svizzera Italiana (IOSI) Recruiting
Bellinzona, Switzerland, 6500
Contact: Ricardo Pereira Mestre, MD    +41 91 811 84 46    ricardo.pereiramestre@eoc.ch   
Principal Investigator: Ricardo Pereira Mestre, MD         
Kantonsspital Graubuenden Recruiting
Chur, Switzerland, 7000
Contact: Richard Cathomas, MD    +41 81 256 66 95    richard.cathomas@ksgr.ch   
Principal Investigator: Richard Cathomas, MD         
Spital Thurgau AG Recruiting
Frauenfeld, Switzerland, CH-8500
Contact: Regina Woelkly, MD    +41 52 723 76 91    regina.woelkly@stgag.ch   
Principal Investigator: Regina Woelkly, MD         
Hôpitaux Universitaires de Genève Recruiting
Genève 14, Switzerland, 1211
Contact: Nicolas Mach, Prof    +41 22 372 98 81    Nicolas.Mach@hcuge.ch   
Principal Investigator: Nicolas Mach, Prof         
CCAC Lausanne Recruiting
Lausanne, Switzerland, 1004
Contact: Pierre Bohanes, MD    +41 (21) 646 79 94    pbohanes@bluewin.ch   
Principal Investigator: Pierre Bohanes, MD         
Luzerner Kantonsspital Recruiting
Luzern 16, Switzerland, 6000
Contact: Beat Müller, MD    +41 41 205 58 60    beat.mueller@luks.ch   
Principal Investigator: Beat Müller, MD         
Hôpital du Valais Recruiting
Martigny, Switzerland, 1920
Contact: Sandro Anchisi, MD    +41 27 603 90 00    sandro.anchisi@hopitalvs.ch   
Principal Investigator: Sandro Anchisi, MD         
Kantonsspital Olten Recruiting
Olten, Switzerland, CH-4600
Contact: Walter Mingrone, MD    41-62-311-4241    wmingrone_ol@spital.ktso.ch   
Principal Investigator: Walter Mingrone, MD         
Hôpital du Valais Recruiting
Sion, Switzerland, 1951
Contact: Sandro Anchisi, MD    +41 27 603 45 00    sandro.anchisi@hopitalvs.ch   
Principal Investigator: Sandro Anchisi, MD         
Bürgerspital Solothurn Recruiting
Solothurn, Switzerland, CH-4500
Contact: Philippe von Burg, MD    +41 32 627 47 00    philippe.vonburg@spital.so.ch   
Principal Investigator: Philippe von Burg, MD         
Kantonsspital St. Gallen Recruiting
St. Gallen, Switzerland, 9007
Contact: Christian Rothermundt, MD    +41 71 494 11 63    christian.rothermundt@kssg.ch   
Principal Investigator: Christian Rothermundt, MD         
Kantonsspital Winterthur Recruiting
Winterthur, Switzerland, 8401
Contact: Natalie Fischer, MD    +41 052 266 40 87    natalie.fischer@ksw.ch   
Principal Investigator: Natalie Fischer, MD         
Stadtspital Triemli Recruiting
Zürich, Switzerland, 8063
Contact: Aleksandra Marek, Dr. med.    +41 (44) 466 11 11    aleksandra.marek@triemli.zuerich.ch   
Principal Investigator: Aleksandra Marek, Dr. med.         
UniversitätsSpital Zürich Recruiting
Zürich, Switzerland, 8091
Contact: Thomas Hermanns, MD    +41 44 255 11 11    thomas.hermanns@usz.ch   
Principal Investigator: Thomas Hermanns, MD         
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
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Study Chair: Christian Rothermundt, MD Cantonal Hospital of St. Gallen

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Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT02640534     History of Changes
Other Study ID Numbers: SAKK 08/14 - IMPROVE
First Posted: December 29, 2015    Key Record Dates
Last Update Posted: January 11, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Swiss Group for Clinical Cancer Research:
Prostate cancer
Cancer of the prostate
Metformin
Enzalutamide
Xtandi
castration resistant prostate cancer
phase II
Androgen deprivation therapy
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs