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

Phase 2

• Conditions: Breast Cancer; Pathological Complete Response; Neoadjuvant Chemotherapy
• Interventions: Drug: Epirubicin; Drug: Fluorouracil; Drug: Docetaxel; Drug: Cyclophosphamide

• Registration Number: NCT03349177
• Lead Sponsor: Zhiyong Yu

Brief Summary

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.

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 Timeline

• Study First Submitted: 2017-10-14
• Status Verified: 2017-11
• Study First Submitted QC: 2017-11-18
• Last Update Submitted: 2017-11-18
• Study First Posted: 2017-11-21
• Last Update Posted: 2017-11-21
• Study Start: 2017-11-27
• Primary Completion: 2019-11-27
• Study Completion: 2019-11-27

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 200

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FEC group	Fluorouracil	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
FEC group	Epirubicin	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
FEC group	Cyclophosphamide	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
EC-T group	Epirubicin	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
EC-T group	Docetaxel	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
EC-T group	Cyclophosphamide	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
TC group	Cyclophosphamide	Docetaxel 75mg/m2 on day 1 and cyclophosphamide 600mg/m2 on day 1 every 3 weeks for six cycles
TC group	Docetaxel	Docetaxel 75mg/m2 on day 1 and cyclophosphamide 600mg/m2 on day 1 every 3 weeks for six cycles

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Pathological Complete Response (pCR)	2 years	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.

Secondary Outcome Measures

Name	Time	Method
The relation between pCR rate, molecular subtypes, and different regiments.	2 years	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.