TNBC Polls & Surveys - Anyone On Clinical Trial with Metforman+Avastin

Purpose

Metformin, a drug that has been used since the 1950's in the treatment of diabetes, has recently generated great interest in its anticancer effects based on in vitro, in vivo and clinical studies. This study assesses the pharmacodynamic effects of metformin on breast cancer metabolism.

The trial design is based on a 2 centre study 'Early Antiangiogenic Response to Bevacizumab in Primary Breast Cancer' that is about to successfully complete recruitment in Oxford and Mount Vernon hospitals. The study takes advantage of the 2 week window between the first clinic visit and commencement of neoadjuvant chemotherapy. Metformin will be given to patients for at least 2 weeks prior to neoadjuvant chemotherapy with a set of 3 breast core biopsies, a PET-CT scan and blood tests carried out before and after this 2 week period of treatment. Patients will also receive a drink of heavy (deuterated) water, a safe and stable isotope commonly used in clinical lipid metabolism studies, the evening prior to both sets of core biopsies. Having completed the first 2 weeks of metformin patients will have the option of continuing metformin until completion of chemotherapy, at the discretion of the trial physician.

The core biopsies will then be used to assess for changes in:

immunohistochemical staining;
gene profiles;
uptake of heavy water into tumour fatty acids using mass spectrometry techniques.

The aim is to identify potential biomarkers of response to metformin (and other future cancer metabolism drugs).

http://www.clinicaltrials.gov/ct2/help/conditions_desc - Condition	http://www.clinicaltrials.gov/ct2/help/interventions_desc - Intervention	http://www.clinicaltrials.gov/ct2/help/phase_desc - Phase
Breast Cancer	Drug: Metformin	Phase II

Study Type:	Interventional
Study Design:	Endpoint Classification: Pharmacodynamics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	A Phase 2 Single Arm Study to Examine the Effects of Metformin on Cancer Metabolism in Patients With Early Stage Breast Cancer Receiving Neoadjuvant Chemotherapy

Resource links provided by NLM:

http://ghr.nlm.nih.gov/ - Genetics Home Reference related topics: http://www.clinicaltrials.gov/ct2/bye/uQoPWw4lZXcilwpxudhWudNzlXNiZip90dcx5Q1PedcOZBUyzB1gWX7gkdNgzwJ. - breast cancer

http://www.nlm.nih.gov/medlineplus/ - MedlinePlus related topics: http://www.clinicaltrials.gov/ct2/bye/WQoPWw4lZX-i-iSxudhWudNzlXNiZip9m67PvQ7xzwhaLwS9pwNHkw-P0B7x061nuQoPmdt. - Breast Cancer http://www.clinicaltrials.gov/ct2/bye/uQoPWw4lZX-i-iSxudhWudNzlXNiZip9m67PvQ7xzwhaLwS90B7x061nuQoPmdt. - Cancer http://www.clinicaltrials.gov/ct2/bye/LQoPWw4lZX-i-iSxudhWudNzlXNiZip9m67PvQ7xzwhaLwS95wNzuQczu6-ikihHSXNkWd7E. - Drinking Water

http://druginfo.nlm.nih.gov/drugportal/drugportal.jsp - Drug Information available for: http://www.clinicaltrials.gov/ct2/bye/YQoPWw4lZXcPSi7iedN6ZXNxvdDxuQ7Ju6c9cXcPSi7iEd-yWB7EZ6o35Q1yzB-VuQUgEscxkd789C7HW6N9Sd7zu. - Metformin http://www.clinicaltrials.gov/ct2/bye/VQoPWw4lZXcPSi7iedN6ZXNxvdDxuQ7Ju6c9cXcPSi7iEd-yWB7EZ6o35Q1yzB-VuQUgEscxkd789C7HW6N9Sd7zuIckx6oyZBckvd-ye6h8. - Metformin hydrochloride

http://www.clinicaltrials.gov/ct2/info/fdalinks - U.S. FDA Resources

Further study details as provided by Oxford Radcliffe Hospitals NHS Trust:

Primary Outcome Measures:

Measure Metformin Induced effects in phosphorylation of S6K, 4E-BP-1 and AMPK via immunohistochemical analysis [ Time Frame: after 14-21 days of daily metforming dosing ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Measure fatty acid desaturation and deuterated water uptake into fatty acids at baseline and after 2 weeks of metformin. [ Time Frame: Day 14-21 after starting metformin dosing ] [ Designated as safety issue: No ]
Measure baseline and induced effect of metformin on upstream and downstream members of AMPK family via gene array analysis. [ Time Frame: 14-21 days after start daily metformin dosing ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	February 2011
Estimated Study Completion Date:	March 2013
Estimated Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

http://www.clinicaltrials.gov/ct2/help/arm_group_desc - Arms	http://www.clinicaltrials.gov/ct2/help/interventions_desc - Assigned Interventions
Metformin: Experimental Intervention: Drug: Metformin	Drug: Metformin Extended release Metformin 1500mg once daily for 14-21 days Other Name: Glucophage XR

Detailed Description:

Metformin is a safe and well tolerated drug that has been widely used in the treatment of diabetes for over 50 years. There is now growing evidence from in vitro laboratory and animal work that metformin has anticancer properties. In addition a retrospective clinical study in a diabetic population has demonstrated evidence of markedly increased pathological response rates (a typically robust surrogate clinical endpoint of efficacy) to pre-surgical chemotherapy in early breast cancer for patients that were also taking metformin as part of their diabetes treatment.

There are several studies of metformin in cancer patients ongoing or being developed worldwide These are predominantly in relatively unselected cancer populations and with clinical outcomes as endpoints. However this study is the only study currently planned which will carry out a substantial assessment of pharmacodynamic endpoints. It is important that this study is carried out at an early stage in the development of metformin as a potential cancer therapy in order to ensure that future large scale studies are properly informed.