Clinical trial NCT05334147: Anlotinib Combined With Chemotherapy for the Treatment of HER2 Negative Advanced Breast Cancer
Official title: 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
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: HER2-negative Breast Cancer
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2022-04-19
Enrollment: 315
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HER2 negative advanced breast cancer patients treated with anthracyclines and taxanes

Brief summary: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: up to 1 year after the last patient enrolled
Secondary outcomes:
measure: objective response rate（ORR）
timeFrame: up to 1 year after the last patient enrolled
measure: Clinical benefit rate（CBR）
timeFrame: up to 1 year after the last patient enrolled
measure: overall survival（OS）
timeFrame: up to 1 year after the last patient enrolled
measure: Incidence and Severity of adverse events
timeFrame: up to 1 year after the last patient enrolled
Other outcomes:
Locations:
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Yongmei Yin
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Wei Li
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.