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

Sponsor

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Other)

Overall Status

Completed

CT.gov ID

NCT02742051

Collaborator

(none)

Enrollment

Location

Arms

45.4

Actual Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Everolimus Drug: Letrozole Drug: Fluorouracil Drug: Epirubicin Drug: Cyclophosphamide	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 1, 2016

Actual Primary Completion Date :

Mar 14, 2020

Actual Study Completion Date :

Mar 14, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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)]
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)]
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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.