The effect of metformin on biomarker activity in primary breast cancer - NeoMet Trial

Phase 1

• Conditions: Women with histologically proven operable primary, invasive breast cancer of = 1cm in size. The study will involve women from the east of Scotland.; MedDRA version: 9.1 Level: LLT Classification code 10006190 Term: Breast cancer invasive NOS

• Registration Number: EUCTR2007-000306-70-GB
• Lead Sponsor: niversity of Dundee

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2007-04-26
• Study Completion: 2009-07-19
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 55

Inclusion Criteria

1. Women able to comply with the protocol requirements with primary invasive breast cancer, histologically confirmed by core needle biopsy (see appendix 1: Preparation of core biopsies), with >30% positive malignant epithelial cells on histology, and identified = 1cm tumors on ultrasound and/ or mammography.
2. Tumour measurable by clinical examination, mammography and ultrasound.
3. Adequate bone marrow function as shown by: WBC =3.5 x 109/L, ANC =1.5 x 109/L, Platelets =100, Hb >10g/ dl
4. Adequate liver function as shown by: serum bilirubin = 1.5 x ULN, albumin = 3g/dl, serum transaminases activity = 2.5 x ULN, alkaline phosphatase = 2.5 x ULN
5. Normal renal function (serum creatinine = 1.5 x ULN, BUN 1.5 x ULN)
6. A life expectancy of at least 6 months
7. Written informed consent
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Any degree of renal impairment, measured by serum creatinine = 1.5 x ULN, BUN 1.5 x ULN
2. Known diabetic patients
3. Sepsis
4. Respiratory failure
5. Liver failure
6. Use of iodine-containing X-ray contrast media in the past 2 days.
7. Patients likely to be considered to neo-adjuvant chemotherapy
8. Patients who may require staging involving a contrast CT scan
9. Patients with unstable angina, uncontrolled cardiac disease, or recent myocardial infarction (last 6 months)
10. Evidence of distant metastasis
11. Concomitant anti-cancer treatments such as chemotherapy, immunotherapy/ biological response modifiers (BRM’s), or radiotherapy.
12. Other investigational drugs within the past 30 days or the concomitant use of investigational drugs,
13. History of non-compliance to medical regimens and patients who are considered potentially unreliable
14. Drugs in the same class, or likely to affect the LKB1/ AMPK/ mTOR pathway

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To study the effect of Metformin on the biomarkers of the LKB1/ AMPK/ mTOR network in primary breast cancer;Secondary Objective: To study the effect of Metformin on breast cancer cell proliferation and apoptosis;Primary end point(s): We need to understand the effects of Metformin in humans, to explore its potential anticancer activity and the potential to develop the therapeutic avenue offered by the LKB1/ AMPK/ mTOR pathway. Using metformin as a neo-adjuvant model in breast cancer gives us the ability to look for biochemical changes in the relevant pathways and any evidence of anticancer activity (rather than prevention seen in the epidemiological studies). The neo-adjuvant model also gives an opportunity for sequential biopsy of the same cancer in the same patient at the times of routine clinical assessment with sufficient time for Metformin to take effect.