E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Women with histologically proven operable primary, invasive breast cancer of ≥ 1cm in size. The study will involve women from the east of Scotland. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006190 |
E.1.2 | Term | Breast cancer invasive NOS |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To study the effect of Metformin on the biomarkers of the LKB1/ AMPK/ mTOR network in primary breast cancer |
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E.2.2 | Secondary objectives of the trial |
To study the effect of Metformin on breast cancer cell proliferation and apoptosis |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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We aim to recruit 55 patients in 2 year. If that was not possible, we will extend the trial period until we recruit the 55th patient. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |