Neoadjuvant Toremifene With Melatonin or Metformin in Locally Advanced Breast Cancer

Phase II Multicenter Randomized Study to Compare Neoadjuvant Toremifene With Melatonin or Metformin Versus Toremifene in the Therapy of Locally Advanced Breast

This study evaluates the addition melatonin and metformin to toremifene in the treatment of locally advanced breast cancer. Third of patients will receive toremifene, other third will receive combination of melatonin and toremifene and other patients will receive combination of metformin and toremifene.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Melatonin; Drug: metformin; Drug: Toremifene

Detailed Description

The management of locally advanced breast cancer is complicated issue. Neoadjuvant treatment is often needed to downstage locally advanced ER positive BC tumors prior to surgery. However, many patients do not achieved objective response on 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 anti - estrogen treatment may increase objective response. But, this data is still controversial. We hypothesizes that the combinations of melatonin and metformin with conventional anti - estrogen such as toremifene could be more effective than toremifene 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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age > 18.
• Obtained Inform Concent.
• Morphologically confirmed breast cancer stage IIB, IIIA, IIIB, IIIC ER positive.
• 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.
• Stage IV 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 investigators 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: Toremifene and metformin; Toremifene 60 mg daily with metformin 850 mg BID	Drug: metformin; Other Names: siofor 850; Drug: Toremifene; Other Names: farestone
Experimental: Toremifene and melatonin; Toremifene 60 mg daily with melatonin 3 mg before sleep daily	Drug: Melatonin; Other Names: melaxen; Drug: Toremifene; Other Names: farestone
Active Comparator: Toremifene; Toremifene 60 mg daily	Drug: Toremifene; Other Names: farestone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	Response will evaluate by RECIST criteria	4 months after FPFV
Pathomorphological response	Pathomorphological response will assess after surgery by Miller and Payne Scale	4 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, MD, PhD, DSc, 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, 2022

Study Registration Dates

• First Submitted: July 17, 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, toremifene
• 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; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protective Agents; Hormone Antagonists; Bone Density Conservation Agents; Antioxidants; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Melatonin; Metformin; Toremifene
• Other Study ID Numbers: MBC 2