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

Registration Number
NCT02742051
Lead Sponsor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
40
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Everolimus+LetrozoleEverolimuseverolimus 10mg/d,po + letrozole 2.5mg/d,po \* 18 weeks
Everolimus+LetrozoleLetrozoleeverolimus 10mg/d,po + letrozole 2.5mg/d,po \* 18 weeks
Fluorouracil+epirubicin+cyclophosphamideFluorouracilFluorouracil 600mg/m2,iv,d1 + epirubicin 90mg/m2,iv,d1 + cyclophosphamide 600mg/m2,iv,d1 \* 6 cycles (every 21 days per cycle)
Fluorouracil+epirubicin+cyclophosphamideEpirubicinFluorouracil 600mg/m2,iv,d1 + epirubicin 90mg/m2,iv,d1 + cyclophosphamide 600mg/m2,iv,d1 \* 6 cycles (every 21 days per cycle)
Fluorouracil+epirubicin+cyclophosphamideCyclophosphamideFluorouracil 600mg/m2,iv,d1 + epirubicin 90mg/m2,iv,d1 + cyclophosphamide 600mg/m2,iv,d1 \* 6 cycles (every 21 days per cycle)
Primary Outcome Measures
NameTimeMethod
Feasibility of the trialduring 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
NameTimeMethod
Ultrasound response rateat definitive surgery (18-20 weeks after the first dose of study medication)
Breast-conserving surgery rateat definitive surgery (18-20 weeks after the first dose of study medication)
Peripheral blood CD8+ T cell percentage change in relation to neoadjuvant therapyat definitive surgery (18-20 weeks after the first dose of study medication)
Peripheral blood NK cell percentage change in relation to neoadjuvant therapyat definitive surgery (18-20 weeks after the first dose of study medication)
Peripheral blood T helper cell percentage change in relation to neoadjuvant therapyat definitive surgery (18-20 weeks after the first dose of study medication)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0during on-neoadjuvant therapy period (defined as the period from the first dose of study medication up to 30 days of the last dose)
Pathological complete response (pCR) rateat definitive surgery (18-20 weeks after the first dose of study medication)
Peripheral blood CD4+ T cell percentage change in relation to neoadjuvant therapyat definitive surgery (18-20 weeks after the first dose of study medication)
Peripheral blood regulatory T cell percentage change in relation to neoadjuvant therapyat definitive surgery (18-20 weeks after the first dose of study medication)
Tumor Ki67 index change in ralation to neoadjuvant therapyat definitive surgery (18-20 weeks after the first dose of study medication)
Blood tumor-specific CTLs count change in relation to neoadjuvant therapyat definitive surgery (18-20 weeks after the first dose of study medication)

Trial Locations

Locations (1)

Sun-Yat-Sen Memorial Hospital of Sun-Yat-Sen University

🇨🇳

Guangzhou, Guangdong, China

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