Anlotinib Combined With Chemotherapy for the Treatment of HER2 Negative Advanced Breast Cancer (ALOT-BC1)

Anlotinib Combined With Chemotherapy for the Treatment of HER2 Negative Advanced Breast Cancer Previously Treated With Anthracyclines and Taxanes: A Multicenter, Prospective, Observational Clinical Study

The study is being conducted to evaluate the efficacy and safety of anlotinib combined with chemotherapy treatment for patients with HER2 negative advanced breast cancer previously received anthracyclines and taxanes

Study Overview

• Status: Not yet recruiting
• Conditions: HER2-negative Breast Cancer

Detailed Description

Breast cancer is the most frequent malignancy in women worldwide. Treatments on HER2 negative breast cancer are still under exploration. Therefore, it is imperative to find a novel therapy to treat these patients.

Anlotinib is an anti-angiogenic small-molecule butyrate kinase inhibitor, and preliminary phase II study results show that anlotinib has good efficacy and tolerability in the treatment of HER-2-negative advanced breast cancer.

This study is a prospective, multicenter, observational clinical study that will collect and report anlotinib in combination with anlotinib in patients with HER2-negative advanced breast cancer treated with anthracyclines and taxanes in a real-world clinical setting Efficacy and safety data for chemotherapy treatments.

• Study Type: Observational
• Enrollment (Anticipated): 315

Contacts and Locations

• Study Contact: Name: Wei Li; Phone Number: 0086-13851603656; Email: real.lw@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

HER2 negative advanced breast cancer patients treated with anthracyclines and taxanes

Description

Inclusion Criteria:

1. Age ≥18 years old (calculated on the day of signing informed consent);
2. Histologically diagnosed advanced breast cancer, including inoperable locally advanced breast cancer or recurrent/metastatic breast cancer;
3. Immunohistochemical detection of HER-2 (-) or (1+), of which HER-2 (2+) must be tested by FISH and the result is negative;
4. All patients have previously underwent chemotherapy containing anthracyclines and taxanes (adjuvant, neoadjuvant or rescue therapy) , and treatment failure or disease progression received at most two chemotherapy regimens after recurrence/metastasis. HR+/HER2- breast cancer patients need to complete endocrine drug therapy;
5. Physical condition ECOG PS: 0-1;
6. There is at least 1 measurable lesion of metastasis according to RECIST 1.1;
7. The patients voluntarily joined the project and signed the informed consent.

Exclusion Criteria:

1. Pregnant or lactating women;
2. Patients with a previous history of breast cancer were excluded, except for ipsilateral DCIS who received only local therapy ≥5 years ago; patients with a history of any other cancer (except non-melanoma skin cancer or cervical carcinoma in situ) were excluded;
3. allergic to Anlotinib;
4. Received eribulin, capecitabine treatment or anti-angiogenic drug treatment in the past;
5. Uncontrolled brain metastases (except asymptomatic, or patients with stable brain metastases receiving local treatment);
6. According to the judgment of the investigator, there are concomitant diseases that seriously endanger the patient's safety or affect the patient's completion of the study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Anlotinib in combination with chemotherapy; anlotinib12mg qd p.o. d1-14/21day/cycle；eribulin 1.4 mg/m2，d1&d8/21day/cycle；capecitabine 1000 mg/m2，bid，d1-14/21day/cycle.
chemotherapy; eribulin 1.4 mg/m2，d1&d8/21day/cycle；capecitabine 1000 mg/m2，bid，d1-14/21day/cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS will be defined as the time from first dose of study drug until documentation of disease progression or death from any cause	up to 1 year after the last patient enrolled

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate（ORR）	The ORR will be defined as the proportion of patients in the Efficacy Evaluable patient Set who achieve complete response (CR) and partial response (PR)	up to 1 year after the last patient enrolled
Clinical benefit rate（CBR）	Proportion of patients with a complete response (CR), partial response (PR), and stable disease (SD) ≥24 weeks in the best objective tumor response	up to 1 year after the last patient enrolled
overall survival（OS）	The time from the patient's initiation of treatment to death from any cause	up to 1 year after the last patient enrolled
Incidence and Severity of adverse events	AE grade were defined by the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events).	up to 1 year after the last patient enrolled

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Investigators: Principal Investigator: yongmei Yin, The First Affiliated Hospital with Nanjing Medical University; Study Director: Wei Li, The First Affiliated Hospital with Nanjing Medical University

Publications and helpful links

General Publications

• Gonzalez-Angulo AM, Morales-Vasquez F, Hortobagyi GN. Overview of resistance to systemic therapy in patients with breast cancer. Adv Exp Med Biol. 2007;608:1-22. doi: 10.1007/978-0-387-74039-3_1.
• Banerjee S, Dowsett M, Ashworth A, Martin LA. Mechanisms of disease: angiogenesis and the management of breast cancer. Nat Clin Pract Oncol. 2007 Sep;4(9):536-50. doi: 10.1038/ncponc0905.
• Ranpura V, Hapani S, Wu S. Treatment-related mortality with bevacizumab in cancer patients: a meta-analysis. JAMA. 2011 Feb 2;305(5):487-94. doi: 10.1001/jama.2011.51. Erratum In: JAMA. 2011 Jun 8;305(22):2294.
• Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007 Dec 27;357(26):2666-76. doi: 10.1056/NEJMoa072113.
• Hu N, Si Y, Yue J, Sun T, Wang X, Jia Z, Gao S, Li Q, Shao Y, Wang J, Luo Y, Ma F, Xu B, Yuan P. Anlotinib has good efficacy and low toxicity: a phase II study of anlotinib in pre-treated HER-2 negative metastatic breast cancer. Cancer Biol Med. 2021 Mar 12;18(3):849-59. doi: 10.20892/j.issn.2095-3941.2020.0463. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): April 15, 2022
• Primary Completion (ANTICIPATED): February 1, 2025
• Study Completion (ANTICIPATED): September 1, 2025

Study Registration Dates

• First Submitted: April 11, 2022
• First Submitted That Met QC Criteria: April 18, 2022
• First Posted (ACTUAL): April 19, 2022

Study Record Updates

• Last Update Posted (ACTUAL): April 19, 2022
• Last Update Submitted That Met QC Criteria: April 18, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 2021-SR-592

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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