Neoadjuvant FDC With Melatonin or Metformin for Locally Advanced Breast Cancer. (MBC1)

Phase II Multicenter Randomized Study to Compare Neoadjuvant FDC With Melatonin or Metformin Versus FDC Alone in The Therapy of Locally Advanced Breast Cancer.

This study evaluates the addition melatonin and metformin to conventional chemotherapy FDC (Fluoruracil, Doxorubicin, cyclophosphamide) in the treatment of locally advanced breast cancer. Third of patients will receive FDCх6 cycles, other third will receive combination of melatonin and FDCх6 cycles and other patients will receive combination of metformin and FDCх6 cycles.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: metformin; Drug: melatonin; Drug: Fluoruracil

Detailed Description

The treatment of locally advanced breast cancer is a complicated issue. For neoadjuvant treatment is often needed to downstage locally advanced BC tumors prior to surgery, however many patients do not achieved objective response during treatment. The ability of melatonin and metformin to decrease side effects of chemotherapy had been investigated, moreover several studies confirm, that this drugs in combination with conventional treatment may increase objective response. But, this data is still controversial. We hypothesized that combinations of melatonin and conventional chemotherapy regimen such as FDC could be more effective than FDC alone in terms of response rate.

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tatiana Y Semiglazova, MD, PhD, DSc; Phone Number: +79219468072; Email: tsemiglazova@mail.ru

Study Locations

• Russian Federation
  • Saint - Petersburg, Russian Federation, 191124
    • Recruiting
    • N.N. Petrov Research Institute of Oncology Clinical Diagnostic Department
    • Contact: Tatiana Y Semiglazova, MD, PhD, DSc; Phone Number: +79219468072; Email: tsemiglazova@mail.ru
    • Sub-Investigator: Petr V Krivorotko, MD, PhD, DSc
    • Principal Investigator: Tatiana Y Semiglazova, MD, PhD, DSc
    • Contact: Michael A Osipov, MD; Phone Number: +79052075653; Email: Ocipovmixail@mail.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age >18. Obtained Inform Consent Morphologically confirmed breast cancer stage IIB, IIIA,IIIB,IIIC. ( triple negative, luminal B) Eastern Collaborative Oncology Group Performance Status Scale 0 - 2. Expected survival >6 month Adequate liver and bone marrow function

Exclusion Criteria:

• Systemic treatment for breast cancer IV stage disease Evidence of liver and bone marrow clinically meaningful disfunction Severe uncontrolled concomitant conditions and diseases Pregnancy or lactation Second malignancy Diabetes mellitus requiring drug therapy Any condition preventing study participation by investigator opinion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FDC x 6 cycles with metformin; 32 patients will receive 5 - Fluoruracil 500 mg/m^2, doxorubicin 50 mg/m^2, cyclophosphamide 500 mg/m^2 once every 21 days with metformin 850 mg BID	Drug: Cyclophosphamide; Other Names: endoxan; Drug: Doxorubicin; Other Names: Adriablastin; Drug: metformin; Other Names: siofor 850; Drug: Fluoruracil
Experimental: FDC x 6 cycles with melatonin; 32 patients will receive 5 - Fluoruracil 500 mg/m^2, doxorubicin 50 mg/m^2, cyclophosphamide 500 mg/m^2 once every 21 days with melatonin 3 mg before sleep daily	Drug: Cyclophosphamide; Other Names: endoxan; Drug: Doxorubicin; Other Names: Adriablastin; Drug: melatonin; Other Names: melaxen; Drug: Fluoruracil
Active Comparator: FDC x 6 cycles; 32 patients will receive 5 - Fluoruracil 500 mg/m^2, doxorubicin 50 mg/m^2, cyclophosphamide 500 mg/m^2 once every 21 days	Drug: Cyclophosphamide; Other Names: endoxan; Drug: Doxorubicin; Other Names: Adriablastin; Drug: Fluoruracil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	Response will evaluate by RECIST criteria	6 months after FPFV
Pathomorphological response	Pathomorphological response will assess after surgery by Miller and Payne Scale	6 months after FPFV

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events incidence	Incidence of AE classified using NCI Common Terminology Criteria for AE v4	Until 30 days after last patient treatment visit

Collaborators and Investigators

• Sponsor: N.N. Petrov National Medical Research Center of Oncology
• Investigators: Study Director: Vladimir F Semiglazov, MD, PhD, DSc, Professor, N.N. Petrov Research Institute Of Oncology; Principal Investigator: Tatiana Y Semiglazova, N.N. Petrov Research Institute Of Oncology

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Anticipated): August 1, 2020
• Study Completion (Anticipated): August 1, 2020

Study Registration Dates

• First Submitted: July 21, 2015
• First Submitted That Met QC Criteria: July 22, 2015
• First Posted (Estimate): July 23, 2015

Study Record Updates

• Last Update Posted (Actual): September 4, 2019
• Last Update Submitted That Met QC Criteria: September 2, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Melatonin, metformin, chemotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Antioxidants; Cyclophosphamide; Fluorouracil; Melatonin; Metformin; Doxorubicin
• Other Study ID Numbers: MBC1