A window of opportunity study investigating biological effects of metformin in localised prostate cancer

Phase 1

Conditions: Prostate cancer
MedDRA version: 19.1Level: PTClassification code 10060862Term: Prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-005193-11-GB

Lead Sponsor: King's College London

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Male

Target Recruitment: Not specified

Inclusion Criteria

1. Age 18 or older and willing and able to provide signed informed consent.
2. Histologically confirmed adenocarcinoma of the prostate , with a maximal tumour length of greater or equal to 6mm on core biopsy
3. No previous treatment for prostate cancer (including surgery, any hormone therapy, radiotherapy and cryotherapy)
4. Prostate biopsy within 6 months from screening.
5. Radical prostatectomy is the scheduled treatment of choice
6. Eastern Cooperative Oncology Group (ECOG) Performance status less than or equal to 0 or 1.
7. Adequate organ function, defined as follows:
Haemoglobin >10.0g/dL
Absolute neutrophil count >1.5x109/L
Platelet count >100x109/L
Renal function, eGFR >60ml/min (calculated by Cockcroft Gault)
AST and/or ALT <2.5 x ULN
Total Bilirubin <1.5 x ULN
8. Able to swallow the drug and comply with study requirements.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion Criteria

1. Patients with a current or historical diagnosis of type one or two Diabetes and/or have ever received metformin
2. Patients with hypersensitivity to any of the components of Metformin or placebo tablet
3. History of or conditions associated with lactic acidosis such as shock or pulmonary insufficiency, alcoholism (acute or chronic), and conditions associated with hypoxaemia
4. Patients with chronic liver disease, severe cardiovascular impairment, cardiac failure, recent myocardial infarction, severe peripheral vascular disease or renal impairment (eGFR <60ml/min as measured by Cockcroft Gault)
5. Patients with acute severe disorders, for example infections with fever, pancreatitis, trauma, dehydration or reduced diet (<1000kcal or 4200kJ per day)
6. Other active malignancy over the last five years that has required systemic therapy, excluding:
a. Adjuvant therapy in the curative setting
b. Non-melanoma skin cancer
c. Superficial transitional cell carcinoma (CIS-T1)
7. Current enrolment in an investigational drug or device study or participation in such a study within 30 days of signing consent.
8. Any subjects who is able to father a child and does not agree to use barrier protection, in the form of a condom ,for the duration of the trial and for 16 weeks after the last study drug administration.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the biological effect of metformin on markers of the FASN/AMPK pathway in prostate tissue by comparison of pre and post-treatment samples.;Secondary Objective: To evaluate the biological effect of metformin on markers of proliferation in prostate tissue by comparison of pre and post-treatment samples. <br><br>To evaluate differences in expression levels of FASN/AMPK-associated biomarkers in benign and malignant prostate tissue<br><br>To measure metformin levels in prostate tissue <br><br>To determine safety of metformin in this non-diabetic patient cohort<br><br>To determine surgical toxicity;Primary end point(s): Assessment of the difference in expression levels of markers of the FASN/AMPK pathway pre and post treatment between the placebo and metformin arms.;Timepoint(s) of evaluation of this end point: The primary endpoint will be completed pre and post 5 weeks of treatment with the IMP.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Assessment of the difference in expression levels of indicators of proliferation (ki67 and TUNEL) pre and post treatment between the placebo and metformin arms. <br><br>Assessment of the difference in expression levels of markers of the FASN/AMPK pathway and indicators of proliferation between benign and malignant prostate tissue in the placebo and metformin arms. <br><br>Assessment of the difference in metformin levels in baseline and post-treatment prostate tissue. <br><br>Assessment of adverse events and laboratory evaluations.<br><br>Assessment of surgical-specific toxicities: time between biopsy and surgery, peri-operative bleeding, infection, rectal injury and length of hospital stay.;Timepoint(s) of evaluation of this end point: All secondary endpoints will be completed pre and post 5 weeks of treatment with the IMP.