Anlotinib Combined With Chemotherapy and Neoadjuvant Therapy for Hormone Receptor-positive HER-2 Negative Breast Cancer (ACNTBC)

Anlotinib Plus Chemotherapy as Neoadjuvant Treatment of High-risk, Early-stage Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer: A Prospective, Single-arm, Single-center, Phase II Clinical Study

Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Combining anti-angiogenesis with chemotherapy yielded increased response rates in patients with early-stage human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This study aims to evaluate the efficacy and safety of adding anlotinib to standard neoadjuvant chemotherapy in primary (HER2)-negative breast cancer. Patients aged 18 years or older with previously untreated stage ⅡB-IIIA histologically documented (HER2)-negative breast cancer were assigned to receive chemotherapy plus oral Anlotinib. The primary endpoint was pathologic complete response (pCR) (no invasive carcinoma in breast or axilla). Secondary end points included safety and disease-free survival (DFS).

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer Stage II
• Intervention / Treatment: Drug: Anlotinib

Detailed Description

Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Combining anti-angiogenesis with chemotherapy yielded increased response rates in patients with early-stage human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This phase II study aims to evaluate the efficacy and safety of adding anlotinib to standard neoadjuvant chemotherapy in primary (HER2)-negative breast cancer.

Patients aged 18 years or older with previously untreated stage ⅡB-IIIA histologically documented (HER2)-negative breast cancer were assigned to receive chemotherapy plus oral Anlotinib (12 mg qd, d1-14; 21 days per cycle; total 5 cycles). Chemotherapy comprised of pirarubicin at 50 mg/m2 and cyclophosphamide at 500 mg/m2 and albumin-bound paclitaxel at 200 mg/m2, (d1, 21 days per cycle; both total 6 cycles), which was then followed by surgery. The primary endpoint was pathologic complete response (pCR) (no invasive carcinoma in breast or axilla). Secondary end points included safety and disease-free survival (DFS). Stratification was based on the clinical breast cancer stage .

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ting Wang, PhD; Phone Number: 0086-13700283101; Email: ting_w100@126.com

Study Locations

• China
  • Shannxi Province
    • Xi'an, Shannxi Province, China, 710032
      • Recruiting
      • Xijing Hospital Affiliated to Air Force Military Medical University
      • Contact: Ting Wang, PhD; Phone Number: 0086-13700283101; Email: ting_w100@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• All patients were HER2 negative, defi ned as munohistochemistry of 0/1+, or if 2+, fl uorescence insitu hybridisation showed no evidence of amplifi cation of the HER2 gene.
• Patients were required to have a palpable primary tumor at least 2.0 cm in diameter in the breast, as assessed by physical examination, and to be classified as having tumor stage T1c to T3, nodal stage N0 to N2a, and metastasis stage M0.
• Other eligibility criteria adequate cardiac function (left ventricular ejection fraction within the normal institutional range, as assessed by multiplegated acquisition scan or echocardiogram), adequate bone marrow, hepatic, and renal function, and appropriate Eastern Cooperative Oncology Group (ECOG) performance status (0-2).
• All patients provided written informed consent.

Exclusion Criteria:

• Previously received anti-angiogenesis targeted drug therapy.
• patients have previous diagnosis of ischaemic heart disease, cerebrovascular disease, peripheral vascular disease, arterial or venous thromboembolic disease, cardiac failure, gastroduodenal ulcer, symptomatic diverticulitis, or inflammatory bowel disease.
• Previously received chemotherapy, radiotherapy, or endocrine therapy as treatment for breast cancer was allowed.
• No uncont rolled hypertension.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anlotinib; Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Anlotinib (12 mg qd, d1-14; 21 days per cycle; total 5 cycles) Combined TAC×6 cycles.	Drug: Anlotinib; Anlotinib (12 mg qd, d1-14; 21 days per cycle; total 5 cycles) Combined TAC×6 cycles: albumin-bound paclitaxel (200mg/m2, 1d Q3W) + pirarubicin （50mg/m2, 1d Q3W) + cyclophosphamide (500mg/m2, 1d Q3W); Other Names: TAC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR( pathological complete remission)	Pathological complete remission rate assessed by the investigator	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ADR	Adverse Drug Reactions	8 weeks
DFS	DFS(Disease-free survival)	8 weeks

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Principal Investigator: Ting Wang, PhD, Xijing Hospital Affiliated to Air Force Military Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): November 30, 2022
• Primary Completion (Anticipated): July 30, 2023
• Study Completion (Anticipated): July 30, 2025

Study Registration Dates

• First Submitted: July 19, 2022
• First Submitted That Met QC Criteria: September 25, 2022
• First Posted (Actual): September 28, 2022

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 25, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Breast cancer Antivascular drugs Neoadjuvant therapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: KY20202075-F-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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