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Neoadjuvant Paclitaxel Plus Epirubicin Versus Vinorelbine Plus Epirubicin in Breast Cancer With TEKT4 Variations

Primary Purpose

Breast Cancer

Status

Completed

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Vinorelbine plus Epirubicin

Paclitaxel plus Epirubicin

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Breast cancer, Neoadjuvant chemotherapy, TEKT4

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Age: 18-70 years old
Expected survival > 12 months
Baseline ECOG Performance Status rating 0-1
Naïve to chemotherapy or hormonal treatments
Radiologically confirmed and biopsy diagnosed invasive ductal carcinoma of breast and prepared to be treated surgically
Locally advance breast cancer of stage IIb-IIIc
HER-2 negative confirmed by immunohistochemistry, Ki-67≥20%
TEKT4 variation confirmed by DNA sequencing
No concurrent malignancy (except controlled cervical carcinoma in situ or basal cell carcinoma of skin)
Patients have measurable lesions (according to RECIST v1.1 criteria)
Intention to cooperate with baseline puncture and neoadjuvant therapy
No advanced metastasis or metastasis involving brain or liver
Adequate bone marrow function, blood routine examination shows neutrophil count ≥ 1.5x109/L, hemoglobin level ≥ 100 g/L, Platelets ≥ 100 x 109/L
Adequate liver and kidney function, serum aminotransferase (AST) ≤ 60U/L, serum total bilirubin ≤ 2.5 times ULN, serum creatinine ≤110μmol/L, urea nitrogen ≤7.1mmol/L
No coagulation abnormality
Normal heart function, with normal ECG and LVEF ≥ 55%
Women of childbearing age agree to take reliable contraceptive measures during clinical trials, and negative serum or urine pregnancy test within 7 days prior to administration
No coagulation abnormality
Sign the informed consent statement and voluntarily receive follow-ups, treatments, laboratory tests and other research procedures according to protocol.

Exclusion Criteria:

Previous regional or systemic treatment for breast cancer (include but not limited to chemotherapy, radiotherapy, targeted therapy, other clinical trials)
Inflammatory breast cancer, bilateral breast cancer or breast cancer already with distant metastasis
Complicated with uncontrolled lung disease, severe infection, active peptic ulcer, blood clotting disorders, severe uncontrolled diabetes, connective tissue disorders or bone marrow suppression, and intolerance to neoadjuvant therapy or related treatment
Peripheral neuropathy >1 degree caused by any reason
History of congestive heart failure, uncontrolled or symptomatic angina, arrhythmias or history of myocardial infarction, refractory hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg);
Breast cancer during lactation or pregnancy
Unwillingly to receive baseline puncture or neoadjuvant therapy
Mental illness or incompliance to treatment caused by other reasons
Known history of severe hypersusceptibility to any agents used in the treatment protocol
Patients received major surgery or suffered from severe trauma within 2 months of first administration
Currently enroll or recently used (30 days within enrollment) other agent under research or involved in other trial
Known to be infected with human immunodeficiency virus (HIV)
Other circumstances considered to be inappropriate to be enrolled by researchers

Sites / Locations

Fudan University Shanghai Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Paclitaxel plus Epirubicin

Vinorelbine plus Epirubicin

Arm Description

Paclitaxel plus Epirubicin for 4 cycles, paclitaxel 80 mg/m2 IV on day 1, 8 and 15, epirubicin 90 mg/m2 IV on day 1, and dosing interval is 21 days.

Vinorelbine plus Epirubicin for 4 cycles, vinorelbine 25 mg/m2 IV on day 1, 8 and 15, epirubicin 90 mg/m2 IV on day 1, and dosing interval is 21 days.

Outcomes

Primary Outcome Measures

pathologic Complete Response (pCR)

pCR is defined as the absence of noninvasive tumor residuals in breast and axillary lymph nodes (ypT0/is ypN0) after neoadjuvant therapy.

Secondary Outcome Measures

Objective Response Rate (ORR)

ORR is defined as the proportion of patients who achieved a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Full Information

NCT ID

NCT02628613

First Posted

December 5, 2015

Last Updated

October 30, 2019

Sponsor

Fudan University

1. Study Identification

Unique Protocol Identification Number

NCT02628613

Brief Title

Neoadjuvant Paclitaxel Plus Epirubicin Versus Vinorelbine Plus Epirubicin in Breast Cancer With TEKT4 Variations

Official Title

Phase II Randomized Clinical Trial and Biomarker Analysis of Paclitaxel Plus Epirubicin Versus Vinorelbine Plus Epirubicin as Neoadjuvant Chemotherapy in Locally Advanced HER2-Negative Breast Cancer With TEKT4 Variations

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

December 2015 (Actual)

Primary Completion Date

February 2019 (Actual)

Study Completion Date

February 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Fudan University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to compare the efficiency and safety between paclitaxel combined with epirubicin and vinorelbine combined with epirubicin when used in neoadjuvant chemotherapy for locally advanced (IIb-IIIc) HER2-negative breast cancer with TEKT4 variations.

Detailed Description

Taxane-based chemotherapy is the cornerstone treating breast cancer, however remarkable percentage of breast cancer patients presents with primary or secondary taxane resistance. Currently no established biomarker has been reported clinically for predicting taxane sensitivity. Our previous study indicated that TEKT4 variation decreased the stability of intracellular microtubule, and TEKT4 variant cells behaves higher resistance to microtubule-stabilizing agents such as taxane, while enhanced sensibility to microtubule depolymerization agents such as vinorelbine. This study is intended to confirm that TEKT4 variation predicts the prognosis of taxane-based chemotherapy through the prospective clinical trials. This study intends to evaluate the efficiency and safety of two neoadjuvant therapies: paclitaxel combined with epirubicin and vinorelbine combined with epirubicin, in treating locally advanced (IIb-IIIc) HER2-negative breast cancer with TEKT4 variation. Primary endpoint of study: pathologic Complete Response (pCR). Secondary endpoints of the study: Objective response rate (CR+PR). Exploratory endpoint: Based on pretreatment tumor and matched blood samples, the correlation between biomarker and efficiency is explored. This open single center prospective randomized control study includes patients locally advanced (IIb-IIIc) HER2-negative patients with TEKT4 variation diagnosed with histopathology and Sanger sequencing. Patients randomized to Group A or Group B to receive respective neoadjuvant chemotherapy. Among which Group A: PE x 4 cycles (paclitaxel + epirubicin), paclitaxel: 80 mg/m2 IV on day 1, 8 and 15; epirubicin: 90 mg/m2 IV on day 1, and dosing interval is 21 days. Group B: NE x 4 cycles (vinorelbine + epirubicin), vinorelbine: 25 mg/m2 IV on day 1, 8 and 15; epirubicin: 90 mg/m2 IV on day 1, and dosing interval is 21 days. Patients of both groups were performed with diagnostic puncture before treatment and over half of treatment course in order to obtain information about dynamic change of Ki67 and other parameters; Surgery will be performed after 4 cycles of chemotherapy, followed with subsequent adjuvant therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

Breast cancer, Neoadjuvant chemotherapy, TEKT4

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

91 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Paclitaxel plus Epirubicin

Arm Type

Active Comparator

Arm Description

Paclitaxel plus Epirubicin for 4 cycles, paclitaxel 80 mg/m2 IV on day 1, 8 and 15, epirubicin 90 mg/m2 IV on day 1, and dosing interval is 21 days.

Arm Title

Vinorelbine plus Epirubicin

Arm Type

Experimental

Arm Description

Vinorelbine plus Epirubicin for 4 cycles, vinorelbine 25 mg/m2 IV on day 1, 8 and 15, epirubicin 90 mg/m2 IV on day 1, and dosing interval is 21 days.

Intervention Type

Drug

Intervention Name(s)

Vinorelbine plus Epirubicin

Intervention Description

Evaluate the efficiency and safety of vinorelbine plus epirubicin as neoadjuvant chemotherapy in locally advanced HER2-negative breast cancer with TEKT4 variations

Intervention Type

Drug

Intervention Name(s)

Paclitaxel plus Epirubicin

Intervention Description

standard neoadjuvant chemotherapy

Primary Outcome Measure Information:

Title

pathologic Complete Response (pCR)

Description

pCR is defined as the absence of noninvasive tumor residuals in breast and axillary lymph nodes (ypT0/is ypN0) after neoadjuvant therapy.

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Objective Response Rate (ORR)

Description

ORR is defined as the proportion of patients who achieved a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Time Frame

3 years

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age: 18-70 years old Expected survival > 12 months Baseline ECOG Performance Status rating 0-1 Naïve to chemotherapy or hormonal treatments Radiologically confirmed and biopsy diagnosed invasive ductal carcinoma of breast and prepared to be treated surgically Locally advance breast cancer of stage IIb-IIIc HER-2 negative confirmed by immunohistochemistry, Ki-67≥20% TEKT4 variation confirmed by DNA sequencing No concurrent malignancy (except controlled cervical carcinoma in situ or basal cell carcinoma of skin) Patients have measurable lesions (according to RECIST v1.1 criteria) Intention to cooperate with baseline puncture and neoadjuvant therapy No advanced metastasis or metastasis involving brain or liver Adequate bone marrow function, blood routine examination shows neutrophil count ≥ 1.5x109/L, hemoglobin level ≥ 100 g/L, Platelets ≥ 100 x 109/L Adequate liver and kidney function, serum aminotransferase (AST) ≤ 60U/L, serum total bilirubin ≤ 2.5 times ULN, serum creatinine ≤110μmol/L, urea nitrogen ≤7.1mmol/L No coagulation abnormality Normal heart function, with normal ECG and LVEF ≥ 55% Women of childbearing age agree to take reliable contraceptive measures during clinical trials, and negative serum or urine pregnancy test within 7 days prior to administration No coagulation abnormality Sign the informed consent statement and voluntarily receive follow-ups, treatments, laboratory tests and other research procedures according to protocol. Exclusion Criteria: Previous regional or systemic treatment for breast cancer (include but not limited to chemotherapy, radiotherapy, targeted therapy, other clinical trials) Inflammatory breast cancer, bilateral breast cancer or breast cancer already with distant metastasis Complicated with uncontrolled lung disease, severe infection, active peptic ulcer, blood clotting disorders, severe uncontrolled diabetes, connective tissue disorders or bone marrow suppression, and intolerance to neoadjuvant therapy or related treatment Peripheral neuropathy >1 degree caused by any reason History of congestive heart failure, uncontrolled or symptomatic angina, arrhythmias or history of myocardial infarction, refractory hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg); Breast cancer during lactation or pregnancy Unwillingly to receive baseline puncture or neoadjuvant therapy Mental illness or incompliance to treatment caused by other reasons Known history of severe hypersusceptibility to any agents used in the treatment protocol Patients received major surgery or suffered from severe trauma within 2 months of first administration Currently enroll or recently used (30 days within enrollment) other agent under research or involved in other trial Known to be infected with human immunodeficiency virus (HIV) Other circumstances considered to be inappropriate to be enrolled by researchers

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zhimin Shao, MD.PhD.

Organizational Affiliation

Fudan University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Fudan University Shanghai Cancer Center

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200032

Country

China

12. IPD Sharing Statement

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Neoadjuvant Paclitaxel Plus Epirubicin Versus Vinorelbine Plus Epirubicin in Breast Cancer With TEKT4 Variations

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