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

Phase 2

Recruiting

• Conditions: Breast Cancer Stage II
• Interventions: Drug: Anlotinib

• Registration Number: NCT05558722
• Lead Sponsor: Xijing Hospital

Brief Summary

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).

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 Timeline

• Study First Submitted: 2022-07-19
• Status Verified: 2022-09
• Study First Submitted QC: 2022-09-25
• Last Update Submitted: 2022-09-25
• Study First Posted: 2022-09-28
• Last Update Posted: 2022-09-28
• Study Start: 2022-11-30
• Primary Completion: 2023-07-30
• Study Completion: 2025-07-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Anlotinib	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.

Primary Outcome Measures

Name	Time	Method
pCR( pathological complete remission)	8 weeks	Pathological complete remission rate assessed by the investigator

Secondary Outcome Measures

Name	Time	Method
ADR	8 weeks	Adverse Drug Reactions
DFS	8 weeks	DFS(Disease-free survival)

Trial Locations

Locations (1)

Xijing Hospital Affiliated to Air Force Military Medical University; 🇨🇳 Xi'an, Shannxi Province, China