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

Breast Cancer Clinical Trial

— APP  

Official title:

Neoadjuvant Apatinib Added to Weekly Paclitaxel and Cisplatin in Patient With Locally Advanced or Early Stage HER2 Negative Breast Cancer (APP) : a Open-label, Randomized, Controlled, Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03982485
• Other study ID #: SHPD005
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 16, 2018
• Est. completion date: March 29, 2031

Study information

• Verified date: April 2024
• Source: RenJi Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 196
• Est. completion date: March 29, 2031
• Est. primary completion date: March 29, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Apatinib
Apatinib 250mg, Oral, day 2,3,4,5,6,7, every week
• Paclitaxel
Paclitaxel 80mg/m2, Intravenous, day 1, 8, 15, 22, every 28 days for a cycle
• Cisplatin
Cisplatin 25mg/m2, Intravenous, day 1, 8, 15, every 28 days for a cycle

Procedure:
• Surgery
Surgery

Locations

Country	Name	City	State
China	Renji Hospital, School of Medicine, Shanghai Jiao Tong University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
RenJi Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Residual cancer burden (RCB 0-I rates)	RCB 0-I rates means RCB 0+I (good response) rates.	Time of surgery
Primary	Pathologic Complete Response (pCR) of the Primary Tumor in the Breast	Percentage of patients absent of histologic evidence of invasive tumor cells in the surgical breast specimen.	Time of surgery
Secondary	pCR in the Breast and Nodes	Percentage of patients absent of histologic evidence of invasive tumor cells in the surgical breast specimen and axillary lymph nodes.	Time of surgery
Secondary	Near pCR in the Breast	Percentage of patients with the residual breast lump Less than 10%	Time of surgery
Secondary	Clinical and imaging response	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	Time of surgery
Secondary	Number of Participants With Drug Related Treatment Adverse Events	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.	an average of 16 weeks
Secondary	Neo-bioscore	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	Time of surgery
Secondary	Disease-free Survival (DFS)	DFS is defined as the time period between registration and first event	Measured through 5 years after study enrollment
Secondary	Distant-disease- free survival (DDFS)	DDFS is defined as the time period between registration and first event	Measured through 5 years after study enrollment
Secondary	Overall survival (OS)	OS is defined as the time period between registration and first event	Measured through 5 years after study enrollment