Clinical trial NCT01314833: Minus Anthracycline or Short-Term Versus Epirubicin and Cyclophosphamide Followed by Paclitaxel Regimen for Adjuvant Breast Cancer Therapy
Official title: 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 HER2-negative Operable Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Breast Cancer
Keywords: Luminal A
Luminal B
TNBC
DFS
DDFS
OS
Lead sponsor: Fudan University
Sponsor class: OTHER
Collaborators: name: Chinese Anti-Cancer Association
First posted: 2011-03-15
Enrollment: 1570
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)
* 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.

Primary outcomes:
measure: Disease-Free Survival
timeFrame: 5 years
Secondary outcomes:
measure: Distant Disease-Free Survival
timeFrame: 5 years
measure: Overall Survival
timeFrame: 5 years
measure: Adverse Events
timeFrame: through chemotherapy completion, an average of 6 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
References:
citation: Jones S, Holmes FA, O'Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, Pippen JE, Bordelon JH, Kirby RL, Sandbach J, Hyman WJ, Richards DA, Mennel RG, Boehm KA, Meyer WG, Asmar L, Mackey D, Riedel S, Muss H, Savin MA. Docetaxel With Cyclophosphamide Is Associated With an Overall Survival Benefit Compared With Doxorubicin and Cyclophosphamide: 7-Year Follow-Up of US Oncology Research Trial 9735. J Clin Oncol. 2009 Mar 10;27(8):1177-83. doi: 10.1200/JCO.2008.18.4028. Epub 2009 Feb 9.