Combination Neoadjuvant Chemotherapy With or Without Apatinib for HER2 Negative Breast Cancer

Phase 2

Active, not recruiting

• Conditions: Breast Cancer
• Interventions: Drug: Apatinib; Drug: Paclitaxel; Drug: Cisplatin; Procedure: Surgery

• Registration Number: NCT03982485
• Lead Sponsor: RenJi Hospital

Brief Summary

RATIONALE:

The combination of anti-angiogenic targeted therapy with neoadjuvant chemotherapy has been shown to further improve the pathologic response rate for HER2-negative breast cancer patients. Apatinib is a highly potent human vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitor that has been independently developed in China, and it can exert anti-angiogenic effects by inhibiting VEGFR2. It is unknown whether giving combination neoadjuvant chemotherapy together with apatinib is more effective in treating patients with nonmetastatic HER2-negative breast cancer.

PURPOSE:

To explore the efficacy and safety of apatinib added to weekly paclitaxel and cisplatin neoadjuvant therapy for HER-2 negative breast cancer patients

Detailed Description

Not available

Study Timeline

• Study Start: 2018-10-16
• Study First Submitted: 2019-04-10
• Study First Submitted QC: 2019-06-10
• Study First Posted: 2019-06-11
• Primary Completion: 2023-03-29
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-28
• Last Update Posted: 2024-04-30
• Study Completion: 2031-03-29

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 196

Inclusion Criteria

1. 18~70 year-old，Female
2. Patients with histologically confirmed primary invasive breast adenocarcinoma,cT2-4N0-3M0
3. ECOG 0-1
4. HER2-negative tumor in biopsy, defined as: Immunohistochemical (IHC) 0-1+ or IHC 2+ confirmed as FISH negative.
5. Adequate organ function

Exclusion Criteria

1. Unwilling to use adequate contraceptive protection during the process of the study and for at least 8 weeks after the last dose of study drug.
2. Pregnant or breastfeeding patients
3. Metastatic or recurrent patients
4. Any evidence of sense or motor nerve disorders
5. Any concurrent malignancy other than breast cancer
6. Uncontrolled hypertension with hypotensive drugs therapy (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg). Patients with grade I or above myocardial ischemia or myocardial infarction or arrhythmia (including QT interval ≥ 440 ms) or cardiac insufficiency
7. Inability to swallow, gastrointestinal resection, chronic diarrhea and obstruction of the intestine, various factors which affect drug use and absorption
8. Coagulation disorders
9. Artery or venous thrombosis occurred within 6 months before the study begins
10. Have received prior treatment with a VEGFR TKI

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I	Apatinib	Apatinib+Paclitaxel+Cisplatin
Arm I	Surgery	Apatinib+Paclitaxel+Cisplatin
Arm II	Surgery	Paclitaxel+Cisplatin
Arm I	Paclitaxel	Apatinib+Paclitaxel+Cisplatin
Arm II	Paclitaxel	Paclitaxel+Cisplatin
Arm I	Cisplatin	Apatinib+Paclitaxel+Cisplatin
Arm II	Cisplatin	Paclitaxel+Cisplatin

Primary Outcome Measures

Name	Time	Method
Pathologic Complete Response (pCR) of the Primary Tumor in the Breast	Time of surgery	Percentage of patients absent of histologic evidence of invasive tumor cells in the surgical breast specimen.
Residual cancer burden (RCB 0-I rates）	Time of surgery	RCB 0-I rates means RCB 0+I (good response) rates.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Drug Related Treatment Adverse Events	an average of 16 weeks	Adverse events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state.
Disease-free Survival (DFS)	Measured through 5 years after study enrollment	DFS is defined as the time period between registration and first event
Overall survival (OS)	Measured through 5 years after study enrollment	OS is defined as the time period between registration and first event
pCR in the Breast and Nodes	Time of surgery	Percentage of patients absent of histologic evidence of invasive tumor cells in the surgical breast specimen and axillary lymph nodes.
Neo-bioscore	Time of surgery	The Neo-Bioscore staging points were determined for each patient based on information from the medical records according to the previously published work（Mittendorf EA, et al. The Neo-Bioscore Update for Staging Breast Cancer Treated With Neoadjuvant Chemotherapy: Incorporation of Prognostic Biologic Factors Into Staging After Treatment. JAMA Oncol. United States; 2016;2:929-36.）.; Neo-Bioscore = Clinical stages score + Pathological stages score + Tumor marker score Clinical stage I =0, Clinical stage IIA =0, Clinical stage IIB =1, Clinical stage IIIA =1, Clinical stage IIIB =2, Clinical stage IIIC =2, Pathological stage 0 =0, Pathological stage I =0, Pathological stage IIA =1, Pathological stage IIB =1, Pathological l stage IIIA =1, Pathological stage IIIB =1, Pathological stage IIIC =2, Tumor marker ER negative=1 Tumor marker Grade3=1 Tumor marker ERBB2 negative=1
Near pCR in the Breast	Time of surgery	Percentage of patients with the residual breast lump Less than 10%
Distant-disease- free survival (DDFS)	Measured through 5 years after study enrollment	DDFS is defined as the time period between registration and first event
Clinical and imaging response	Time of surgery	To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests. (sonography, mammography, or MRI) after treatment

Trial Locations

Locations (1)

Renji Hospital, School of Medicine, Shanghai Jiao Tong University; 🇨🇳 Shanghai, Shanghai, China