Neoadjuvant Chemotherapy With or Without Metformin in Early Breast Cancer.

Metformin is a widely used anti-diabetic drug. Several studies have pointed out a potentially beneficial effect of metformin therapy in diabetic cancer patients. Several studies are investigating the anti-tumor effect of metformin in early breast cancer. However, the enhancing effect of metformin on anti-tumor immunity has only been demonstrated in animal models. This study examines the immune effect of metformin in breast cancer patients treated with preoperative chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Metformin; Drug: Placebo oral tablet

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Osama Hussein; Phone Number: 0020 1099 8151 10; Email: osama.hussein@mail.mcgill.ca

Study Locations

• Egypt
  • Mansoura, Egypt, 35516
    • Recruiting
    • Mansoura University Cancer center
    • Sub-Investigator: Adel Denewer
    • Sub-Investigator: Mosab Shetewy
    • Sub-Investigator: Sameh Roshdy
    • Sub-Investigator: Zyad Emara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically proven breast carcinoma.
• American Society of Anesthesiology (ASA) score I-II.
• Candidate for neoadjuvant chemotherapy as per hospital's protocol.
• Clinically measurable tumor.
• No evidence of distant metastasis.
• Normal renal and liver functions.
• Non-diabetics.

Exclusion Criteria:

• Pregnant or lactating women.
• Metastatic breast cancer patients.
• Patients with hepatic impairment.
• Patients with renal impairment.
• Diabetics.
• Patients unwilling to participate or withdrawing from the trial.
• Psychological/ mental impairment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: metformin group; metformin 850 mg once daily increased within 3 weeks to a maximum dose of 2550 mg on three divided daily doses. Neoadjuvant cytotoxic chemotherapy as per MDT (multi-disciplinary team) decision. Patients scheduled for AC-T (adriamycin, Cyclophosphamide, paclitaxel) or AC (adriamycin, cyclophosphamide) will be eligible to randomization.	Drug: Metformin; Oral hypoglycemic drug. Initial dose 500-850 mg/d. incrementally increased to a maximum daily dose of 2550 mg in three divided doses.; Other Names: Glucophage
PLACEBO_COMPARATOR: Placebo group; placebo. Neoadjuvant cytotoxic chemotherapy as per MDT(multi-disciplinary team) decision. Patients scheduled for AC-T (adriamycin, Cyclophosphamide, paclitaxel) or AC (adriamycin, cyclophosphamide) will be eligible to randomization.	Drug: Placebo oral tablet; Simethicone 60 mg three times daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response rate	Response to preoperative therapy as per ultrasonographic tumor size assessment. A responder will have > 50% decrease in the size of the primary tumor without appearance of new lesions.	at three months from starting therapy.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
T-cell cytotoxic markers.	Percentage of cells staining positive per high power field for the T-cell cytotoxic markers (Granzyme-B, Perforin & CD-8) using immunohistochemistry (IHC).	procedure

Collaborators and Investigators

• Sponsor: Mansoura University
• Investigators: Principal Investigator: Osama Hussein, MD, PhD, Mansoura University Faculty of Medicine

Publications and helpful links

General Publications

• Eikawa S, Nishida M, Mizukami S, Yamazaki C, Nakayama E, Udono H. Immune-mediated antitumor effect by type 2 diabetes drug, metformin. Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1809-14. doi: 10.1073/pnas.1417636112. Epub 2015 Jan 26.
• Pearce EL, Walsh MC, Cejas PJ, Harms GM, Shen H, Wang LS, Jones RG, Choi Y. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature. 2009 Jul 2;460(7251):103-7. doi: 10.1038/nature08097. Epub 2009 Jun 3.
• Coyle C, Cafferty FH, Vale C, Langley RE. Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis. Ann Oncol. 2016 Dec;27(12):2184-2195. doi: 10.1093/annonc/mdw410. Epub 2016 Sep 28.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 5, 2020
• Primary Completion (ANTICIPATED): June 5, 2022
• Study Completion (ANTICIPATED): May 1, 2023

Study Registration Dates

• First Submitted: May 11, 2020
• First Submitted That Met QC Criteria: May 13, 2020
• First Posted (ACTUAL): May 14, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 8, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: breast cancer; metformin; anti-tumor immunity
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: R.20.05.834

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No