Role of Adding Metformin to Neoadjuvant Chemotherapy in Patients With Breast Cancer (METNEO)

NCT04170465 | Completed Phase 2

• 1 other identifier: 919PP18
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Metformin, the widely prescribed oral hypoglycemic drug, is well known for its established efficacy, favorable safety profile, and low cost. Metformin has recently received increasing attention because of its potential antitumorigenic effects that are thought to be independent of its hypoglycemic effects. It has been extensively studied in preclinical models, which have implicated several molecular pathways in its antitumor activity. Metformin was proved to have anti-proliferative and apoptotic effects on tumor cells.Moreover, metformin enhances the T-cell mediated immune response to tumor tissue and fights metastases. Also, epidemiological studies have shown that metformin, but not other antidiabetic drugs, reduces cancer incidence and improves survivability in diabetic cancer patients. The proposed research in this application will investigate two prime questions with regards to the combined use of metformin together with traditional neoadjuvant chemotherapy in breast cancer patients. First, the hypothesis that the simultaneous use of metformin along with doxorubicin/cyclophosphamide/paclitaxel neoadjuvant protocol produces better antitumor outcomes will be tested. Second, the study will examine if the improved apoptotic effect of such regimen is paralleled by exaggerated stimulatory influences on apoptosis biomarkers.

Conditions

Breast Cancer Female

Keywords

Metformin; locally advanced breast cancer; neoadjuvant

Outcome Measures

Primary Outcomes (2)

• Evaluation of the effect on tumor apoptosis

  Tissue level of the apoptosis biomarker in the excised tumor.

  6 months

• Chemotherapy toxicities

  Monitoring the incidence of chemotherapy toxicities during neoadjuvant therapy

  6 months

Secondary Outcomes (1)

• Pathologic complete response rate (pCR)

  6 months

Study Arms (2)

Metformin group

EXPERIMENTAL

Patients will receive AC-T neoadjuvant chemotherapy in addition to oral metformin HCl (850 mg tablets, twice per day, for 6 months) (n= 30)

Drug: Metformin Hydrochloride 850 mg Tablets; Drug: AC-T chemotherapy regimen

Control group

ACTIVE COMPARATOR

Patients will receive AC-T neoadjuvant chemotherapy alone (n= 30)

Drug: AC-T chemotherapy regimen

Interventions

Metformin Hydrochloride 850 mg Tablets DRUG

Oral administration of Metformin hydrochloride 850 mg tablets (1700 mg/day) daily until the completion of neoadjuvant chemotherapy cycles

Also known as: Cidophage 850 mg

Metformin group

AC-T chemotherapy regimen DRUG

AC: (Doxorubicin 60 mg/m2 IV + cyclophosphamide 600 mg/m2 IV) for 4 cycles every 3 weeks followed by Taxol cycles (Paclitaxel 80 mg/m2 IV) once weekly for 12 weeks.

Also known as: AC (doxorubicin [Adriamycin] + cyclophosphamide) followed by paclitaxel (Taxol)

Control group; Metformin group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females ≥ 18 years of age and \< 65 years.
• Unilateral or bilateral primary carcinoma of the breast confirmed.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2.
• Clinically measurable tumor size who are candidates for neoadjuvant therapy.
• No evidence of distant metastasis.
• Normal renal and liver functions.
• Non-diabetics.

You may not qualify if:

• Pregnant or breastfeeding women.
• Prior cancer chemotherapy.
• Heart disease or reduced cardiac output with left ventricular ejection fraction \< 50%.
• Metastatic breast cancer patients.
• Patients with hepatic impairment.
• Patients with renal impairment.
• Diabetics.

Sponsors & Collaborators

• Damanhour University: lead
• Alexandria University: collaborator

Study Sites (1)

Damanhour University

Beheira, 22511, Egypt

Location

Related Publications (2)

• Serageldin MA, El-Bassiouny NA, El-Kerm Y, Aly RG, Helmy MW, El-Mas MM, Kassem AB. A randomized controlled study of neoadjuvant metformin with chemotherapy in nondiabetic breast cancer women: The METNEO study. Br J Clin Pharmacol. 2024 Dec;90(12):3160-3175. doi: 10.1111/bcp.16193. Epub 2024 Aug 7.

  PMID: 39113190 DERIVED

• Serageldin MA, Kassem AB, El-Kerm Y, Helmy MW, El-Mas MM, El-Bassiouny NA. The Effect of Metformin on Chemotherapy-Induced Toxicities in Non-diabetic Breast Cancer Patients: A Randomised Controlled Study. Drug Saf. 2023 Jun;46(6):587-599. doi: 10.1007/s40264-023-01305-4. Epub 2023 May 2.

  PMID: 37131014 DERIVED

MeSH Terms

Interventions

Metformin; Doxorubicin; Cyclophosphamide; Paclitaxel

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Study Officials

• Mahmoud M El-Mas, PhD

  Professor in Pharmacology, Faculty of Pharmacy, Alexandria University

  STUDY DIRECTOR

• Yasser M El-Kerm, PhD

  Professor in Clinical Oncology, Medical Research Institute,Alexandria University

  STUDY DIRECTOR

• Maged W Helmy, PhD

  Professor in Pharmacology, Faculty of pharmacy, Damanhour University

  STUDY CHAIR

• Amira B Kassem, PhD

  Lecturer in Clinical Pharmacy, Faculty of Pharmacy, Damanhour University

  STUDY CHAIR

• Noha A El-Bassiouny, PhD

  Lecturer in Clinical Pharmacy, Faculty of Pharmacy, Damanhour University

  STUDY CHAIR

• Manar A Serageldin, Bachelor

  Teaching assistant in Pharmacology, Faculty of Pharmacy, Alexandria University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized Controlled Trial

Study Record Dates

• First Submitted: November 18, 2019
• First Posted: November 20, 2019
• Study Start: October 29, 2019
• Primary Completion: April 2, 2022
• Study Completion: June 28, 2022
• Last Updated: September 10, 2022

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)