Clinical trial NCT02628613: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Breast cancer
Neoadjuvant chemotherapy
TEKT4
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2015-12-11
Enrollment: 91
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Age: 18-70 years old
2. Expected survival \> 12 months
3. Baseline ECOG Performance Status rating 0-1
4. Naïve to chemotherapy or hormonal treatments
5. Radiologically confirmed and biopsy diagnosed invasive ductal carcinoma of breast and prepared to be treated surgically
6. Locally advance breast cancer of stage IIb-IIIc
7. HER-2 negative confirmed by immunohistochemistry, Ki-67≥20%
8. TEKT4 variation confirmed by DNA sequencing
9. No concurrent malignancy (except controlled cervical carcinoma in situ or basal cell carcinoma of skin)
10. Patients have measurable lesions (according to RECIST v1.1 criteria)
11. Intention to cooperate with baseline puncture and neoadjuvant therapy
12. No advanced metastasis or metastasis involving brain or liver
13. Adequate bone marrow function, blood routine examination shows neutrophil count ≥ 1.5x109/L, hemoglobin level ≥ 100 g/L, Platelets ≥ 100 x 109/L
14. 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
15. No coagulation abnormality
16. Normal heart function, with normal ECG and LVEF ≥ 55%
17. 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
18. No coagulation abnormality
19. Sign the informed consent statement and voluntarily receive follow-ups, treatments, laboratory tests and other research procedures according to protocol.

Exclusion Criteria:

1. Previous regional or systemic treatment for breast cancer (include but not limited to chemotherapy, radiotherapy, targeted therapy, other clinical trials)
2. Inflammatory breast cancer, bilateral breast cancer or breast cancer already with distant metastasis
3. 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
4. Peripheral neuropathy \>1 degree caused by any reason
5. 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);
6. Breast cancer during lactation or pregnancy
7. Unwillingly to receive baseline puncture or neoadjuvant therapy
8. Mental illness or incompliance to treatment caused by other reasons
9. Known history of severe hypersusceptibility to any agents used in the treatment protocol
10. Patients received major surgery or suffered from severe trauma within 2 months of first administration
11. Currently enroll or recently used (30 days within enrollment) other agent under research or involved in other trial
12. Known to be infected with human immunodeficiency virus (HIV)
13. Other circumstances considered to be inappropriate to be enrolled by researchers

Primary outcomes:
measure: pathologic Complete Response (pCR)
timeFrame: 3 years
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 3 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Zhimin Shao, MD.PhD.
role: PRINCIPAL_INVESTIGATOR
References: