Apatinib in Neoadjuvant Therapy for Patients With Breast Cancer

Study Overview
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Brief Summary
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To verify the role of apatinib in neoadjuvant therapy for breast cancer, the investigators designed a prospective, randomized, parallel-controlled phase II/III trial, to investigate the efficacy and safety of apatinib combined with TP (paclitaxel + cisplatin) or TP regimen alone as neoadjuvant therapy for stage II-III breast cancer treatment. 100 cases of eligible patients were diagnosed by core needle biopsy and immunohistochemistry, with the molecular subtypes of triple-negative, HER2+ or Luminal B, evaluated by pathological complete remission (pCR), objective response rate (ORR), adverse events, disease free survival (DFS) and OS, aiming at providing a new way for neoadjuvant therapy in breast cancer and anti-angiogenic treatment of malignant tumors.

Official Title
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Efficacy and Safety of Apatinib Added to Docetaxel and Cisplatin Neoadjuvant Therapy for Patients With Breast Cancer: a Randomized, Parallel Controlled Phase II Trial

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Apatinib
* Drug: paclitaxel
* Drug: cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: breast invasive carcinoma diagnosed by core needle biopsy, without previous treatments for breast cancer; with the molecular subtypes of triple-negative, HER2+ or Luminal B, confirmed by immunohistochemistry; breast cancer within stage IIb-IIIc, planned to receive neoadjuvant therapy; women aged from 18 to 70 years old; required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; left ventricular ejection fraction (LVEF) greater than 55% without clinical symptoms or signs of heart failure; Adequate bone marrow, with white blood cell ≥4.0×109 /L，neutrophils ≥2.0×109 /L, platelet ≥100×109 /L, hemoglobin ≥ 90 g/L； Serum creatinine ranges from 44 to 133 mol/L; Glutamic pyruvic transaminase and Glutamic-oxalacetic Transaminase ≤2 times to superior limit of normal value; bilirubin ≤ superior limit of normal value; Expected survival ≥ 12 months; pregnancy tests must be negative, and the couples of patients should agree to use effective contraception during treatment and the following one year; approved by the institutional ethnics committee of the Fourth Hospital of Hebei Medical University, with signature to the Informed consent. Exclusion Criteria: severe systemic infection; being allergic or intolerant to apatinib, paclitaxel, cisplatin; having received any testing drugs, radiotherapy or other chemotherapy drugs within 30 days before being enrolled in this trial; uncontrolled hypertension, severe heart function; researchers believe that participating in the test does not meet the best interests of the patients (e.g. cause adverse health) or may interfere with the evaluation of response.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: apatinib+TP<br>TP neoadjuvant chemotherapy (paclitaxel 165mg/m2 day 1, cisplatin 40mg, day 1-3) combined with apatinib (received TP concurrently with apatinib 500mg, day1-21). | Drug: Apatinib<br>* 500mg, day1-21,neoadjuvant therapy<br>Drug: paclitaxel<br>* paclitaxel 165mg/m2 day 1<br>Drug: cisplatin<br>* cisplatin 40mg, day 1-3<br>|
| Sham Comparator: TP<br>TP neoadjuvant chemotherapy alone (paclitaxel 165mg/m2 day 1, cisplatin 40mg, day 1-3). | Drug: paclitaxel<br>* paclitaxel 165mg/m2 day 1<br>Drug: cisplatin<br>* cisplatin 40mg, day 1-3<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is pathological complete remission (pCR) | pCR was defined as no histological evidence of invasive tumor cells in the surgical breast specimen and draining nodes. The presence of residual ductal carcinoma-in situ was not included in the pCR category after neoadjuvant treatment. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The second endpoint includes the objective response rate (ORR) | Evaluation of tumor response was performed by independent evaluators who were blinded to the arm assignment consisted of 2 oncologists and 2 pathologists. Tumor response status was defined according to the Response Evaluation Criteria in Solid Tumors Committee (RECIST). Specifically, the complete response (CR) was defined as the disappearance of all the lesions both in breast specimen and draining nodes; The primary endpoint ORR composed of tumor response classifications of CR and partial response (PR). | 4 months | 
| Adverse events (AE) | Adverse events (AE) were monitored on an ongoing basis and classified according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0. Patients were assessed for toxicities before each administration., and toxicity was graded accordingly. | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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apatinib, neoadjuvant therapy, breast cancer