Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04170465
Recruitment Status : Recruiting
First Posted : November 20, 2019
Last Update Posted : July 29, 2020
Sponsor:
Collaborator:
Alexandria University
Information provided by (Responsible Party):
Damanhour University

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.


Condition or disease Intervention/treatment Phase
Breast Cancer Female Drug: Metformin Hydrochloride 850 mg Tablets Drug: AC-T chemotherapy regimen Phase 2

Detailed Description:
  1. Ethical committee approval will be obtained from Ethics committee of Faculty of Pharmacy, Damanhour University.
  2. All participants should agree to take part in this clinical study and will provide informed consent.
  3. Sixty female breast cancer patients, who are candidates for neoadjuvant chemotherapy, will be recruited from the Medical Research Institute, Oncology department, Alexandria University, Alexandria.
  4. The 60 participants will be randomly assigned into 2 arms:

    • Control arm (n=30): will be treated with AC-Taxol regimen (AC: Doxorubicin 60 mg/m2 IV + cyclophosphamide 600 mg/m2 IV) for 4 cycles every 3 weeks. Subsequent Taxol cycles (Paclitaxel 80mg/m2 IV) once weekly for 12 weeks.
    • Metformin arm (n=30): will be treated with the AC-Taxol regimen mentioned above together with Metformin 850 mg tablets orally twice per day (1700 mg/day).
  5. All patients will be submitted to:

    • Full patient history and clinical examination.
    • Routine follow up before each chemotherapy cycle (complete blood picture, liver function tests, renal function tests).
    • Routine Echocardiography before each chemotherapy cycle.
  6. All patients will be monitored for the incidence of chemotherapy toxicities during neoadjuvant therapy.
  7. After completion of the neoadjuvant therapy, participants will undergo surgical tumor removal. The excised tumor will be collected, and the following biomarkers will be measured:

    i. Ki-67 ii. Caspase-3 iii. TNF-α Also, pathologic complete response (pCR) will be assessed.

  8. Patients demographic data will be recorded with respect to age, weight and disease history.
  9. Statistical tests appropriate to the study design will be conducted to evaluate the significance of the results.
  10. Results, conclusion, discussion and recommendations will be given.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized Controlled Trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Investigation of the Potential Beneficial Effect of Adding Metformin to Neoadjuvant Chemotherapy in Patients With Breast Cancer (METNEO)
Actual Study Start Date : October 29, 2019
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Metformin group
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
Oral administration of Metformin hydrochloride 850 mg tablets (1700 mg/day) daily until the completion of neoadjuvant chemotherapy cycles
Other Name: Cidophage 850 mg

Drug: AC-T chemotherapy regimen
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.
Other Name: AC (doxorubicin [Adriamycin] + cyclophosphamide) followed by paclitaxel (Taxol)

Active Comparator: Control group
Patients will receive AC-T neoadjuvant chemotherapy alone (n= 30)
Drug: AC-T chemotherapy regimen
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.
Other Name: AC (doxorubicin [Adriamycin] + cyclophosphamide) followed by paclitaxel (Taxol)




Primary Outcome Measures :
  1. Evaluation of the effect on tumor proliferation as measured by Ki-67 immunohistochemical (IHC) assessment (%) [ Time Frame: 6 months ]
    Tissue level of Ki-67 expression in the excised tumor. Ki-67 will be scored as the percentage of tumour nuclei staining.

  2. Evaluation of the effect on tumor apoptosis as measured by Caspase-3 [ Time Frame: 6 months ]
    Tissue level of the active caspase-3 in the excised tumor.

  3. Chemotherapy toxicities [ Time Frame: 6 months ]
    Monitoring the incidence of chemotherapy toxicities during neoadjuvant therapy


Secondary Outcome Measures :
  1. Pathologic complete response rate (pCR) [ Time Frame: 6 months ]
    Pathologic complete response rate defined as the absence of residual invasive cancer in the resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. Pregnant or breastfeeding women.
  2. Prior cancer chemotherapy.
  3. Heart disease or reduced cardiac output with left ventricular ejection fraction < 50%.
  4. Metastatic breast cancer patients.
  5. Patients with hepatic impairment.
  6. Patients with renal impairment.
  7. Diabetics.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04170465


Contacts
Layout table for location contacts
Contact: Manar A Serageldin, Bachelor +201229899914 manarserag@hotmail.com
Contact: Amira B Kassem, PhD +201275790327 amirabisher@gmail.com

Locations
Layout table for location information
Egypt
Damanhour University Recruiting
Beheira, Egypt, 22511
Contact: Manar A Serageldin, Bachelor    +201229899914    manarserag@hotmail.com   
Sponsors and Collaborators
Damanhour University
Alexandria University
Investigators
Layout table for investigator information
Study Director: 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 Chair: 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
Principal Investigator: Manar A Serageldin, Bachelor Teaching assistant in Pharmacology, Faculty of Pharmacy, Alexandria University
Layout table for additonal information
Responsible Party: Damanhour University
ClinicalTrials.gov Identifier: NCT04170465    
Other Study ID Numbers: 919PP18
First Posted: November 20, 2019    Key Record Dates
Last Update Posted: July 29, 2020
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Summary of all relevant data will be shared

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Damanhour University:
Metformin
locally advanced breast cancer
neoadjuvant
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Metformin
Paclitaxel
Cyclophosphamide
Doxorubicin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Hypoglycemic Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors