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Note: This record shows only 21 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 21 January 2019
Main ID:  NCT02640534
Date of registration: 22/12/2015
Prospective Registration: Yes
Primary sponsor: Swiss Group for Clinical Cancer Research
Public title: Investigation of Metformin in Patients With Castration Resistant Prostate Cancer in Combination With Enzalutamide vs. Enzalutamide Alone
Scientific 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
Date of first enrolment: March 24, 2016
Target sample size: 168
Recruitment status: Recruiting
URL:  https://clinicaltrials.gov/show/NCT02640534
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 2
Countries of recruitment
Switzerland
Contacts
Name:     Martina Schneider
Address: 
Telephone: +41 31 389 91 91
Email: trials@sakk.ch
Affiliation: 
Name:     Christian Rothermundt, MD
Address: 
Telephone:
Email:
Affiliation:  Cantonal Hospital of St. Gallen
Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: Male
Health Condition(s) or Problem(s) studied
Cancer of the Prostate
Prostate Cancer
Intervention(s)
Drug: Enzalutamide
Drug: Metformin
Primary Outcome(s)
Disease control (DC) [Time Frame: at 15 months]
Secondary Outcome(s)
Adverse events (AEs) [Time Frame: at 15 months]
Event-free survival (EFS) [Time Frame: at 15 months]
Overall response (OR) [Time Frame: at 15 months]
Overall survival (OS) [Time Frame: at 15 months]
Secondary ID(s)
SAKK 08/14 - IMPROVE
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Results
Results available:
Date Posted:
URL:
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