Neoadjuvant Chemo-endocrine Therapy Versus Chemotherapy Alone in ER-positive, HER2-negative Breast Cancer

Phase 3

Completed

• Conditions: Breast Cancer Female
• Interventions: Drug: letrozole, leuprorelin, fluorouracil, epirubicin, cyclophosphamide, docetaxel; Drug: fluorouracil, epirubicin, cyclophosphamide, docetaxel

• Registration Number: NCT02980965
• Lead Sponsor: Fudan University

Brief Summary

This was an open-label, randomized controlled trial that aims to compare the efficacy and safety of the concurrent neoadjuvant chemotherapy with endocrine therapy and neoadjuvant chemotherapy alone in ER-positive, HER2-negative breast cancer.

Detailed Description

Data showed that concurrent neoadjuvant chemotherapy with endocrine therapy was a effective option for ER-positive, HER2-negative breast cancer patients. However this is still a controversial issue. The present study is an open-label randomized controlled clinical trial that aims to investigate the efficacy of concurrent NCT with endocrine therapy (AI with or without GnRH-a) in patients with ER-positive, HER2-negative breast carcinoma.

Study Timeline

• Study Start: 2013-05
• Study First Submitted: 2016-11-26
• Study First Submitted QC: 2016-11-30
• Study First Posted: 2016-12-02
• Primary Completion: 2017-02
• Study Completion: 2017-02
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-08
• Last Update Posted: 2017-11-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 249

Inclusion Criteria

1. Estrogen receptor-positive and HER2-negative breast cancer patients, with histological stage of IIa-IIIc.
2. Without previous chemotherapy or endocrine therapy.
3. ECOG scores of 0-2 points
4. With measurable and evaluable breast tumor pathologically confirmed as invasive ductal carcinoma
5. Age: 18-70 years
6. Lateral breast cancer
7. Normal or acceptable kidney, liver, cardiovascular, and bone marrow functions

Exclusion Criteria

1. Pregnant women or nursing mothers

2. With distant metastasis

3. With a history of malignant tumor or complicated with other malignant tumors in addition to breast cancer, except for non-melanoma skin cancer, in situ cervical cancer or other cured malignant tumor without the basis of recurrence for at least five years

4. With mental illness or other conditions affecting the patient compliance

5. With other serious diseases or medical conditions:

   1. Congestive heart failure or unstable angina pectoris, myocardial infarction within 6 months before the enrollment, uncontrolled hypertension and uncontrolled high-risk arrhythmia considered by the investigator
   2. Obvious neurological or psychiatric disorders, including psychosis, epileptic dementia and other diseases may affect the understanding and sign of the informed consent for
   3. Uncontrolled acute infection

6. Concurrent use of other investigational drugs; or participating in other clinical trials involving investigational drugs within 30 days before this study

7. With allergic constitution and any known or suspected drug allergy

8. Not suitable for the trial considered by the investigator

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
neoadjuvant chemo-endocrine therapy	letrozole, leuprorelin, fluorouracil, epirubicin, cyclophosphamide, docetaxel	In the experimental arm, patients received concurrent chemotherapy (fluorouracil 500mg/m2 IV, epirubicin 90mg/m2 IV and cyclophosphamide 500mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles followed by docetaxel 100mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles; or epirubicin 90mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles, followed by docetaxel 100mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles) with endocrine therapy (letrozole with or without leuprorelin) as a neoadjuvant treatment
neoadjuvant chemotherapy alone	fluorouracil, epirubicin, cyclophosphamide, docetaxel	In the control group, patients received neoadjuvant chemotherapy alone (fluorouracil 500mg/m2 IV, epirubicin 90mg/m2 IV and cyclophosphamide 500mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles followed by docetaxel 100mg/m2 IV on day 1 at 3-weekly intervals for 3 cycles; or epirubicin 90mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles, followed by docetaxel 100mg/m2 IV on day 1 at 2-weekly intervals for 4 cycles)

Primary Outcome Measures

Name	Time	Method
objective response rate (ORR)	4 years	the proportion of patients achieving clinical complete response and partial response in the breast based on magnetic resonance imaging

Secondary Outcome Measures

Name	Time	Method
pathological response rate	4 years	The proportion of patients achieving pathological response based on Miller-Payne grading system
Progression-free survival (DFS)	6 years	The interval between the date of randomization to disease progression during treatment, any recurrence, contralateral breast cancer, the appearance of a second primary cancer, or death not due to cancer, whichever occurred first.
Incidence of Serious Treatment-Emergent Adverse Events(grade 3 or 4)	4 years	Assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.
Ki67 proliferation marker changes	4 years	Absolute Ki67 change as well as geometric mean percentage change in Ki67 positivity
pathologic complete response (pCR)	4 years	Disappearance of residual invasive disease (residual ductal carcinoma in situ allowed) in breast and the absence of positive lymph nodes

Trial Locations

Locations (1)

Cancer Hospital/ Institute, Fudan University; 🇨🇳 Shanghai, Shanghai, China