Minus Anthracycline or Short-Term Versus Epirubicin and Cyclophosphamide Followed by Paclitaxel Regimen for Adjuvant Breast Cancer Therapy

Phase 3

Completed

• Conditions: Primary Breast Cancer
• Interventions: Drug: Docetaxel Cyclophosphamide; Drug: Cyclophosphamide Fluorouracil Epirubicin Docetaxel; Drug: Epirubicin Cyclophosphamide Paclitaxel

• Registration Number: NCT01314833
• Lead Sponsor: Fudan University

Brief Summary

We aimed to evaluate the noninferiority of short-term anthracycline-free chemotherapy (TC, six cycles of docetaxel and cyclophosphamide) or short-term anthracycline-based chemotherapy (CEF-T, three cycles of cyclophosphamide/epirubicin/fluorouracil followed by three cycles of docetaxel) to a standard anthracycline/taxane-containing chemotherapy (EC-P, epirubicin, and cyclophosphamide for four cycles followed by paclitaxel for twelve weeks) in HER2-negative operable breast cancer.

Detailed Description

It was initiated as an adjuvant chemotherapy trial to test noninferiority of an anthracycline-free short-term regimen (T75C600 x 6 \[TC\] once every 3 weeks) or a short-term regimen (C500E100F500 x 3 once every 3 weeks followed by T100 x 3 every 3 weeks \[CEF-T\]) compared with a standard long-term anthracycline-containing regimen (E90C600 x 4 once every 3 weeks followed by P80 x 12 once every week \[EC-P\]) in HER2-negative breast cancer. Patients were randomly assigned (1:1:1) to each arm after completing the surgical excision of the primary tumor.

Study Timeline

• Study Start: 2010-06-01
• Study First Submitted: 2011-03-09
• Study First Submitted QC: 2011-03-14
• Study First Posted: 2011-03-15
• Primary Completion: 2017-06-01
• Study Completion: 2017-06-15
• Status Verified: 2020-05
• Last Update Submitted: 2020-05-17
• Last Update Posted: 2020-05-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 1570

Inclusion Criteria

• Female patients, age at diagnosis 18 - 75 years
• Histological confirmed unilateral primary invasive carcinoma of the breast
• Adequate surgical treatment with complete resection of the tumor (R0) and resection of > or = 10 axillary nodes or SLN in clinically N0 patients
• Node positive disease or node-negative disease with at least one other risk factor (tumor size > or = 2 cm, grade > or = II)
• HER2-negative disease
• No evidence for distant metastasis (M0) after conventional staging
• Performance Status ECOG < or = 1
• The patient must be accessible for treatment and follow-up
• LVEF> 50%
• Negative pregnancy test (urine or serum) within 7 days prior to randomization in premenopausal patients
• Leucocytes > or = 4 x 10^9/L
• platelets > or = 100 x 10^9/L
• haemoglobin > or = 9 g/dL
• total bilirubin < or = 1.5 UNL
• ASAT (SGOT) and ALAT (SGPT) < or = 2.5 UNL
• creatinine < 175 mmol/L (2 mg/dL)

Exclusion Criteria

1. Has received neoadjuvant therapy (include chemotherapy, targeted therapy, radiotherapy or endocrine therapy）;
2. Has bilateral breast cancer;
3. Has the previous history of additional malignancy, with the exception of adequately treated basal cell carcinoma and cervical carcinoma in situ.
4. Has metastatic (Stage 4) breast cancer;
5. Has any >T4 lesion (UICC1987) (with skin involvement, mass adhesion and fixation, and inflammatory breast cancer);
6. Is pregnant, is breastfeeding women, or women of childbearing age who cannot practice effective contraceptives;
7. Patients participating in other clinical trials at the same time;
8. Has severe organ dysfunction (cardiopulmonary liver and kidney) insufficiency, left ventricular ejection fraction (LVEF) < 50% (cardiac ultrasound); severe cardio cerebral vascular disease within the 6 months previous of randomization (such as unstable angina, chronic heart failure, uncontrolled hypertension with blood pressure>150/90mmgh, myocardial infarction, or cerebral blood vessel); diabetic patients with poor blood glucose control; patients with severe hypertension;
9. Has known allergy to taxane and excipients;
10. Has severe or uncontrolled infection.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TC*6	Docetaxel Cyclophosphamide	6 cycles of (Docetaxel 75mg/m2 ivgtt d1+ Cyclophosphamide 600 mg/m2 iv d1, 21 days per cycle) .
CEF*3-T*3	Cyclophosphamide Fluorouracil Epirubicin Docetaxel	3 cycles of CEF (Epirubicin 100 mg/m2 ivgtt d1+Cyclophosphamide 500 mg/m2 iv d1+ 5-fluorouracil 500 mg/m2 iv d1, 21 days per cycle) followed by 3 cycles of Docetaxel (Docetaxel 100mg/m2, ivgtt d1, 21 days per cycle)
EC*4-wP*12	Epirubicin Cyclophosphamide Paclitaxel	4 cycles of EC (Epirubicin 90 mg/m2 ivgtt d1+Cyclophosphamide 600 mg/m2 iv d1, 21 days per cycle) followed by 4 cycles of Paclitaxel (Paclitaxel 80mg/m2, ivgtt d1,8,15, 21days per cycle)

Primary Outcome Measures

Name	Time	Method
Disease-Free Survival	5 years	Defined as the time from randomization to occurrence of a new event including local recurrence, regional relapse, distant metastasis, contralateral primary breast cancer, second non-breast invasive cancer (excluding non-melanoma skin cancers), or death from any cause.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	5 years	defined as the time from randomization to death from any cause
Adverse Events	through chemotherapy completion, an average of 6 months	Number of Participants with Adverse Events
Distant Disease-Free Survival	5 years	Defined as the time from randomization to the earliest recurrence outside of the ipsilateral locoregional region or to death from any cause, whenever a death occurred before distant recurrence

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China