Pathological Complete Response Rate in Locally Advanced Breast Cancer With FEC, EC-T, or TC as Neoadjuvant Chemotherapy

Pathological Complete Response Rate in Locally Advanced Breast Cancer With Neoadjuvant Fluorourcil/Epirubicin/Cyclophosphamide, Epirubicin/Cyclophosphamide Followed by Docetaxel, or Docetaxel/Cyclophosphamide as Neoadjuvant Chemotherapy

Neoadjuvant chemotherapy (NAC) has become the standard therapy for both locally advanced and early-stage breast cancer in recent years for the improvement breast conserving surgery rate and the evaluation of treatment response in vivo. Pathological complete response (pCR) is an independent prognostic factor irrespective of breast cancer intrinsic subtypes after NAC. The trial is designed to compare effectiveness between anthracycline and/or taxane as neoadjuvant chemotherapy for operable advanced breast cancer in different molecular typing. In this trial the investigators will randomly assign 200 primary breast cancer patients to receive six cycles of fluorourcil, epirubicin,and cyclophosphamide(FEC), or four cycles of epirubicin and cyclophosphamide (EC) followed by four cycles of docetaxel(T), or six cycles of docetaxel and cyclophosphamide (TC). Trasuzumab was recommended combining docetaxel to patients if HER-2 positive.The effectiveness of therapy will be estimated after every two cycles of neoadjuvant chemotherapy. Surgery will be performed after completing designated full cycles of neoadjuvant chemotherapy. The primary endpoint is to assess pathologic complete response (pCR, ypT0/is ypN0) rate in different regiments. The secondary endpoint is to assess the relationship between pCR rate with molecular typing in different regiments, so that the investigators could optimize neoadjuvant chemotherapy regiment according to molecular typing.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer; Neoadjuvant Chemotherapy; Pathological Complete Response
• Intervention / Treatment: Drug: Epirubicin; Drug: Docetaxel; Drug: Fluorouracil; Drug: Cyclophosphamide

Detailed Description

The trial is designed to compare effectiveness between anthracycline and/or taxane as neoadjuvant chemotherapy for operable advanced breast cancer in different molecular typing. In this trial the investigators will randomly assign 200 primary breast cancer patients to receive six cycles of fluorourcil, epirubicin,and cyclophosphamide(FEC), or four cycles of epirubicin and cyclophosphamide (EC) followed by four cycles of docetaxel(T), or six cycles of docetaxel and cyclophosphamide (TC). Trasuzumab was recommended combining docetaxel to patients if HER-2 positive.The effectiveness of therapy will be estimated after every two cycles of neoadjuvant chemotherapy. Surgery will be performed after completing designated full cycles of neoadjuvant chemotherapy. The primary endpoint is to assess pathologic complete response (pCR, ypT0/is ypN0) rate in different regiments. The secondary endpoint is to assess the relationship between pCR rate with molecular typing in different regiments, so that the investigators could optimize neoadjuvant chemotherapy regiment according to molecular typing.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Xiaoshan Cao, MD; Phone Number: 86-15154181183; Email: caoxiaoshan2009@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• All patients were required to give written informed consent.
• Patients present with operable breast cancers that were diagnosed by histopathology and have no distant metastasis.
• Have no history of anti-cancer therapies including chemotherapy, radiation therapy, hormone therapy and surgical therapy.
• Have normal cardiac functions by echocardiography.
• ECOG scores are ≤ 0-1.
• Patients are disposed to practice contraception during the whole trial.
• The results of patients' blood tests are as follows:

Hb ≥ 90 g/L WBC ≥ 3.0×109/L Plt ≥ 100×109/L Neutrophils ≥ 1.5×109/L ALT and AST ≤ 2.5 times of normal upper limit. TBIL ≤ 1.5 times of normal upper limit. Creatinine ≤ 1.5 times of normal upper limit.

Exclusion Criteria:

• Have other cancers at the same time or have the history of other cancers in recent five years, excluding the controlled skin basal cell carcinoma or skin squamous cell carcinoma or carcinoma in situ of cervix.
• Active infections
• Severe non-cancerous diseases.
• The patients are undergoing current administration of anti-cancer therapies, or are attending some other clinical trails.
• Inflammatory breast cancer.
• Pregnant or lactational, or patients refuse to practice contraception during the whole trial.
• The patients are in some special conditions that they can't understand the written informed consent, such as they are demented or hawkish.
• Have allergic history of the chemotherapeutic agents.
• Bilateral breast cancers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: FEC group; Fluorouracil 500mg/m2 on day 1, epirubicin 100mg/m2 on day 1 and cyclophosphamide 500mg/m2 on day 1 every 3 weeks for six cycles	Drug: Epirubicin; 100mg/m2; Other Names: Adriacin; Drug: Fluorouracil; 500mg/m2; Other Names: Fluorouracil injection; Drug: Cyclophosphamide; 500mg/m2(FEC), 600mg/m2(EC-T and TC); Other Names: Cyclophosphamide injection
EXPERIMENTAL: EC-T group; Epirubicin 100mg/m2 on day 1 cyclophosphamide 600mg/m2 on day1 every 2 weeks for four cycles followed by docetaxel 100mg/m2 on day 1 every 3 weeks for four cycles	Drug: Epirubicin; 100mg/m2; Other Names: Adriacin; Drug: Docetaxel; 75mg/m2(TC), 100mg/m2(EC-T); Other Names: Docetaxel injection; Drug: Cyclophosphamide; 500mg/m2(FEC), 600mg/m2(EC-T and TC); Other Names: Cyclophosphamide injection
EXPERIMENTAL: TC group; Docetaxel 75mg/m2 on day 1 and cyclophosphamide 600mg/m2 on day 1 every 3 weeks for six cycles	Drug: Docetaxel; 75mg/m2(TC), 100mg/m2(EC-T); Other Names: Docetaxel injection; Drug: Cyclophosphamide; 500mg/m2(FEC), 600mg/m2(EC-T and TC); Other Names: Cyclophosphamide injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Pathological Complete Response (pCR)	Participants were evaluated following eight cycles of treatment and after surgery to assess for pCR. pCR was defined as no invasive or in situ residual tumor masses in the breast and lymph nodes according to pathologist examination. The percentage of participants with pCR was reported, and the 95% CI for one-sample binomial was constructed using the Pearson-Clopper method.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The relation between pCR rate, molecular subtypes, and different regiments.	The correlations were calculated using the Spearman rank correlation coefficient. The criteria for judging the size of the correlation coefficient were applied: correlations<0.30 are considered minor, correlations between 0.3-0.49 are considered medium, and ≥0.5 are considered strong. Cohen's kappa statistic was used to determine inter-examiner agreement. According to Altman's guidelines, it is poor when kappa scores ≤0.20, fair when kappa between 0.21-0.40, moderate when kappa between 0.41-0.60, good when kappa 0.61-0.80, and very good when kappa ≥0.80.	2 years

Collaborators and Investigators

• Sponsor: Zhiyong Yu
• Investigators: Principal Investigator: Xiaoshan Cao, MD, Shandong Cancer Hospital and Institute

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): November 27, 2017
• Primary Completion (ANTICIPATED): November 27, 2019
• Study Completion (ANTICIPATED): November 27, 2019

Study Registration Dates

• First Submitted: October 14, 2017
• First Submitted That Met QC Criteria: November 18, 2017
• First Posted (ACTUAL): November 21, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 21, 2017
• Last Update Submitted That Met QC Criteria: November 18, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Docetaxel; Cyclophosphamide; Fluorouracil; Epirubicin
• Other Study ID Numbers: ShandongCHI-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No