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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Procedure: Surgery; Drug: Apatinib; Drug: Paclitaxel; Drug: Cisplatin

• Study Type: Interventional
• Enrollment (Actual): 196
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Renji Hospital, School of Medicine, Shanghai Jiao Tong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Apatinib+Paclitaxel+Cisplatin	Procedure: Surgery; Surgery; Drug: Apatinib; Apatinib 250mg, Oral, day 2,3,4,5,6,7, every week; Drug: Paclitaxel; Paclitaxel 80mg/m2, Intravenous, day 1, 8, 15, 22, every 28 days for a cycle; Drug: Cisplatin; Cisplatin 25mg/m2, Intravenous, day 1, 8, 15, every 28 days for a cycle
Active Comparator: Arm II; Paclitaxel+Cisplatin	Procedure: Surgery; Surgery; Drug: Paclitaxel; Paclitaxel 80mg/m2, Intravenous, day 1, 8, 15, 22, every 28 days for a cycle; Drug: Cisplatin; Cisplatin 25mg/m2, Intravenous, day 1, 8, 15, every 28 days for a cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Residual cancer burden (RCB 0-I rates）	RCB 0-I rates means RCB 0+I (good response) rates.	Time of surgery
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Near pCR in the Breast	Percentage of patients with the residual breast lump Less than 10%	Time of surgery
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
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
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
Disease-free Survival (DFS)	DFS is defined as the time period between registration and first event	Measured through 5 years after study enrollment
Distant-disease- free survival (DDFS)	DDFS is defined as the time period between registration and first event	Measured through 5 years after study enrollment
Overall survival (OS)	OS is defined as the time period between registration and first event	Measured through 5 years after study enrollment

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Principal Investigator: Jinsong Lu, MD, Renji Hospital, School of Medicine, Shanghai Jiao Tong University

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2018
• Primary Completion (Actual): March 29, 2023
• Study Completion (Estimated): March 29, 2031

Study Registration Dates

• First Submitted: April 10, 2019
• First Submitted That Met QC Criteria: June 10, 2019
• First Posted (Actual): June 11, 2019

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 28, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Breast cancer; Apatinib; Neoadjuvant chemotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Paclitaxel; Apatinib
• Other Study ID Numbers: SHPD005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No