Clinical Trials /

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

NCT02742051

Description:

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).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Trial of Neoadjuvant Everolimus Plus Letrozole Versus FEC in Women With ER-positive, HER2-negative Breast Cancer
  • Official Title: A Randomised Pilot Study of Neoadjuvant Everolimus Plus Letrozole Compared With FEC in Postmenopausal Patients With ER-positive, HER2-negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 50102016015
  • NCT ID: NCT02742051

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
EverolimusRAD001Everolimus+Letrozole
LetrozoleFemaraEverolimus+Letrozole
Fluorouracil5-FuFluorouracil+epirubicin+cyclophosphamide
EpirubicinEPBFluorouracil+epirubicin+cyclophosphamide
CyclophosphamideCTXFluorouracil+epirubicin+cyclophosphamide

Purpose

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, and to compare the objective response rate. Secondary aims are to compare the response rate by clinical palpation, pathological complete response (pCR) rate, breast-conserving surgery rate, toxicities, and changes in the percentages of peripheral blood CD8+ T cells, T helper cells (Th), regulatory T cells (Treg), and NK cells (pre- versus post- neoadjuvant therapy).

Trial Arms

NameTypeDescriptionInterventions
Everolimus+LetrozoleExperimentaleverolimus 10mg/d,po + letrozole 2.5mg/d,po * 18 weeks
  • Everolimus
  • Letrozole
Fluorouracil+epirubicin+cyclophosphamideActive ComparatorFluorouracil 600mg/m2,iv,d1 + epirubicin 90mg/m2,iv,d1 + cyclophosphamide 600mg/m2,iv,d1 * 6 cycles (every 21 days per cycle)
  • Fluorouracil
  • Epirubicin
  • Cyclophosphamide

Eligibility Criteria

        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.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate
Time Frame:at definitive surgery (18-20 weeks after the first dose of study medication)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Response rate by clinical palpation
Time Frame:at definitive surgery (18-20 weeks after the first dose of study medication)
Safety Issue:
Description:
Measure:Pathological complete response (pCR) rate
Time Frame:at definitive surgery (18-20 weeks after the first dose of study medication)
Safety Issue:
Description:
Measure:Breast-conserving surgery rate
Time Frame:at definitive surgery (18-20 weeks after the first dose of study medication)
Safety Issue:
Description:
Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame:during on-neoadjuvant therapy period (defined as the period from the first dose of study medication up to 30 days of the last dose)
Safety Issue:
Description:
Measure:Peripheral blood CD8+ T cell percentage change in relation to neoadjuvant therapy
Time Frame:at definitive surgery (18-20 weeks after the first dose of study medication)
Safety Issue:
Description:
Measure:Peripheral blood T helper cell percentage change in relation to neoadjuvant therapy
Time Frame:at definitive surgery (18-20 weeks after the first dose of study medication)
Safety Issue:
Description:
Measure:Peripheral blood regulatory T cell percentage change in relation to neoadjuvant therapy
Time Frame:at definitive surgery (18-20 weeks after the first dose of study medication)
Safety Issue:
Description:
Measure:Peripheral blood NK cell percentage change in relation to neoadjuvant therapy
Time Frame:at definitive surgery (18-20 weeks after the first dose of study medication)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Last Updated

May 9, 2017