A Trial of Neoadjuvant Everolimus Plus Letrozole Versus FEC in Women With ER-positive, HER2-negative Breast Cancer

A Randomised Pilot Study of Neoadjuvant Everolimus Plus Letrozole Compared With FEC in Postmenopausal Patients With ER-positive, HER2-negative Breast Cancer

This open, randomized pilot feasibility trial is to evaluate the feasibility and effect of neoadjuvant everolimus plus letrozole versus neoadjuvant fluorouracil, epirubicin plus cyclophosphamide (FEC) in treating postmenopausal women with ER-positive, HER2-negative breast cancer. Forty postmenopausal stage M0, ER-positive, HER2-negative invasive breast cancer women who had a primary tumor > 2cm by imaging or an axillary lymph node > 2cm by imaging were randomly (1:1) enrolled to receive neoadjuvant everolimus plus letrozole for 18 weeks or neoadjuvant FEC for 6 cycles before surgery. The primary objective is to determine the feasibility of neoadjuvant everolimus plus letrozole in postmenopausal patients with ER-positive, HER2-negative breast cancer. Secondary aims are to compare the ultrasound response rate, pathological complete response (pCR) rate, breast-conserving surgery rate, toxicities, and changes in the percentages or counts of peripheral blood CD4+ T cells, CD8+ T cells, tumor-specific CTLs, T helper cells (Th), regulatory T cells (Treg), and NK cells and changes in tumor Ki67 index (pre- versus post- neoadjuvant therapy).

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Everolimus; Drug: Letrozole; Drug: Fluorouracil; Drug: Epirubicin; Drug: Cyclophosphamide

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Sun-Yat-Sen Memorial Hospital of Sun-Yat-Sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• The patients signed the written informed consent
• The patients present with non-metastatic unilateral invasive ER-positive, HER2-negative breast cancer with a primary breast tumor > 2cm by imaging or an axillary lymph node > 2cm by imaging.
• Postmenopausal women with age less than 70 years old.
• The patients have no history of hormone therapy, chemotherapy, breast cancer surgery and radiotherapy.
• The patients have normal cardiac functions by echocardiography.
• The patients' ECOG scores are ≤2.
• The patients can swallow pills.

• The results of patients' blood tests are as follows:

  • Hb≥90g/L;
  • WBC≥4E+9/L;
  • Plt≥100E+9/L;
  • Neutrophils≥1.5E+9/L;
  • ALT and AST ≤ triple of normal upper limit;
  • TBIL ≤ 1.5 times of normal upper limit;
  • Creatinine ≤ 1.5 times of normal upper limit.

Exclusion Criteria:

• The patients have other cancers at the same time or have the history of other cancers except controlled skin basal cell carcinoma or skin squamous cell carcinoma or carcinoma in situ of cervix uterus;
• The patients have active infections that were not suitable for chemotherapy;
• The patients have severe non-cancerous diseases.
• The patients have bilateral breast cancers or multifocal breast cancers or inflammatory breast cancers.
• The patients have a history of previous treatment with mTOR inhibitors.
• The patients are undergoing current administration of anti-cancer therapies, or are attending other clinical trials.
• The patients are in some special conditions that they cannot understand the written informed consent, such as they are demented or hawkish.
• The patients have allergic history or contraindication of any of the interventional drugs.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Everolimus+Letrozole; everolimus 10mg/d,po + letrozole 2.5mg/d,po * 18 weeks	Drug: Everolimus; Neoadjuvant endocrine therapy; Other Names: RAD001; Drug: Letrozole; Neoadjuvant endocrine therapy; Other Names: Femara
Active Comparator: Fluorouracil+epirubicin+cyclophosphamide; Fluorouracil 600mg/m2,iv,d1 + epirubicin 90mg/m2,iv,d1 + cyclophosphamide 600mg/m2,iv,d1 * 6 cycles (every 21 days per cycle)	Drug: Fluorouracil; Neoadjuvant chemotherapy; Other Names: 5-Fu; Drug: Epirubicin; Neoadjuvant chemotherapy; Other Names: EPB; Drug: Cyclophosphamide; Neoadjuvant chemotherapy; Other Names: CTX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Feasibility of the trial	during on-neoadjuvant therapy period (defined as the period from the first dose of study medication up to 30 days of the last dose)

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	during on-neoadjuvant therapy period (defined as the period from the first dose of study medication up to 30 days of the last dose)
Ultrasound response rate	at definitive surgery (18-20 weeks after the first dose of study medication)
Pathological complete response (pCR) rate	at definitive surgery (18-20 weeks after the first dose of study medication)
Breast-conserving surgery rate	at definitive surgery (18-20 weeks after the first dose of study medication)
Peripheral blood CD8+ T cell percentage change in relation to neoadjuvant therapy	at definitive surgery (18-20 weeks after the first dose of study medication)
Peripheral blood T helper cell percentage change in relation to neoadjuvant therapy	at definitive surgery (18-20 weeks after the first dose of study medication)
Peripheral blood regulatory T cell percentage change in relation to neoadjuvant therapy	at definitive surgery (18-20 weeks after the first dose of study medication)
Peripheral blood NK cell percentage change in relation to neoadjuvant therapy	at definitive surgery (18-20 weeks after the first dose of study medication)
Blood tumor-specific CTLs count change in relation to neoadjuvant therapy	at definitive surgery (18-20 weeks after the first dose of study medication)
Peripheral blood CD4+ T cell percentage change in relation to neoadjuvant therapy	at definitive surgery (18-20 weeks after the first dose of study medication)
Tumor Ki67 index change in ralation to neoadjuvant therapy	at definitive surgery (18-20 weeks after the first dose of study medication)

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Investigators: Principal Investigator: Jieqiong Liu, M.D.,Ph.D., Breast Tumor Center, Sun Yat-sen Memorial Hospital

Publications and helpful links

General Publications

• Wu W, Chen J, Deng H, Jin L, He Z, Rao N, Nie Y, Yao Y, Yang Y, Su F, Liu J. Neoadjuvant everolimus plus letrozole versus fluorouracil, epirubicin and cyclophosphamide for ER-positive, HER2-negative breast cancer: a randomized pilot trial. BMC Cancer. 2021 Jul 27;21(1):862. doi: 10.1186/s12885-021-08612-y.
• Wu W, Deng H, Rao N, You N, Yang Y, Cao M, Liu J. Neoadjuvant everolimus plus letrozole versus fluorouracil, epirubicin and cyclophosphamide for ER-positive, HER2-negative breast cancer: study protocol for a randomized pilot trial. Trials. 2017 Oct 25;18(1):497. doi: 10.1186/s13063-017-2228-5.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): March 14, 2020
• Study Completion (Actual): March 14, 2020

Study Registration Dates

• First Submitted: April 7, 2016
• First Submitted That Met QC Criteria: April 15, 2016
• First Posted (Estimate): April 18, 2016

Study Record Updates

• Last Update Posted (Actual): September 23, 2021
• Last Update Submitted That Met QC Criteria: September 22, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Cyclophosphamide; Fluorouracil; Epirubicin; Letrozole; Everolimus
• Other Study ID Numbers: 50102016015

Plan for Individual participant data (IPD)

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