Clinical trial NCT04127019: Adjuvant 6 Cycles of Docetaxel and Cyclophosphamide or 3 Cycles of Cyclophosphamide/Epirubicin/Fluorouracil Followed by 3 Cycles of Docetaxel Versus 4 Cycles of Epirubicin and Cyclophosphamide Followed by Weekly Paclitaxel in Operable Breast Cancer (MASTER)
Official title: Adjuvant Six Cycles of Docetaxel and Cyclophosphamide or Three Cycles of Cyclophosphamide/Epirubicin/Fluorouracil Followed by Three Cycles of Docetaxel Versus Four Cycles of Epirubicin and Cyclophosphamide Followed by Weekly Paclitaxel in Operable Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Breast Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2019-10-15
Enrollment: 2079
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Experimental: Arm 1 6 cycles of (Docetaxel 75mg/m2 ivgtt d1+ Cyclophosphamide 600 mg/m2 iv d1, 21 days per cycle) .

Experimental: Arm 2 3 cycles of FEC (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)

Experimental: Arm 3 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 purpose: TREATMENT

Brief summary: We aimed to evaluate the noninferiority of a short-term anthracycline-free chemotherapy (TC, six cycles of docetaxel and cyclophosphamide) or a 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 operable breast cancer.

Detailed description: It was initiated as an adjuvant chemotherapy trial in 2010 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 \[EC-P\]). Patients were randomly assigned (1:1:1) to each arm after completing surgical excision of primary tumor. Trastuzumab was administered in combination with chemotherapy to patients with HER2-positive breast cancer and sustained monotherapy as per the current guidelines.

Eligibility criteria: 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)
* 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 previous history of additional malignancy, with the exception of adequately treated basal cell carcinoma and cervical carcinoma in situ.
4. Has metastic (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 breast feeding 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.

Primary outcomes:
measure: disease-free survival
timeFrame: 5 year
Secondary outcomes:
measure: distant disease-free survival
timeFrame: 5 year
measure: overall survival
timeFrame: 5 year
Other outcomes:
Locations:
Study officials:
affiliation: Fudan University
name: Zhi-Ming Shao
role: PRINCIPAL_INVESTIGATOR
References: