Fulvestrant Plus Anlotinib in HR(+)/HER2(-) Metastatic Breast Cancer With FGFR Mutation

A Phase II Study of the Efficacy and Tolerability of Fulvestrant Plus Anlotinib in HR(+)/HER2(-) Metastatic Breast Cancer Patients With FGFR Mutation

Previous studies have shown that the FGF signaling pathway is closely related to endocrine therapy resistance in breast cancer, but there is not sufficient evidence for the combination of endocrine therapy and FGFR inhibitors. Anlotinib is a highly effective VEGFRs, FGFRs, PDGFRs multi-target tyrosine kinase inhibitor. Therefore, we conducted this single-arm, single-center phase II clinical study to evaluate the efficacy and the safety of anlotinib combined with fulvestrant in patients with metastatic HR+/HER2- breast cancer patients with FGFR mutation and resistance to aromatase inhibitor therapy, to provide new treatment options for these patients.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Fulvestrant plus Anlotinib

Detailed Description

Endocrine therapy resistance is an unsolved problem in the treatment of HR+/HER2- metastatic breast cancer. Previous studies have shown that the FGF signaling pathway is closely related to endocrine therapy resistance in breast cancer, but there is not sufficient evidence for the combination of endocrine therapy and FGFR inhibitors. Anlotinib is a highly effective VEGFRs, FGFRs, PDGFRs multi-target tyrosine kinase inhibitor, which can effectively block the migration and proliferation of endothelial cells and reduce tumor microvessel density. The drug inhibits VEGFRs, FGFRs, PDGFRs to exert anti-angiogenesis effects and to achieve anti-tumor effects. Therefore, we conducted this single-arm, single-center phase II clinical study to evaluate the efficacy and the safety of anlotinib combined with fulvestrant in patients with metastatic HR-positive and HER2-negative breast cancer patients with FGFR mutation and resistance to aromatase inhibitor therapy, to provide new treatment options for these patients.

• Study Type: Interventional
• Enrollment (Anticipated): 61
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fei Xu, MD; Phone Number: +86-13711277870; Email: xufei@sysucc.org.cn
• Study Contact Backup: Name: Kuikui Jiang, MD; Phone Number: +86-15210589011; Email: jiangkk@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Fei Xu, MD; Phone Number: +86-13711277870; Email: xufei@sysucc.org.cn
      • Principal Investigator: Fei Xu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Voluntarily sign the informed consent form;
2. 18-75 years old;
3. Women in any menstrual state, premenopausal or perimenopausal patients need to receive luteinizing hormone releasing hormone(LHRH) analogue;
4. Eastern Cooperative Oncology Group (ECOG) score [0-1] points;
5. The expected survival period is ≥12 weeks;
6. The diagnosis of invasive carcinoma by histology or cytology; Estrogen receptor (ER) positive (defined as >1% nuclear ER staining); HER2 negative (defined as IHC 0 or 1+, or HER2(2+) with HER2 FISH detection no amplification);
7. Inoperable or recurrent/metastatic breast cancer patients with aromatase inhibitor treatment failure;
8. In the state of disease progression before enrollment;
9. There are FGFR mutations, which meets any of the following: ①Immunohistochemical method: any subtype of FGFR1/2/3/4 is positive; ② Gene detection results of tissue/blood sample shows that any subtype of FGFR1/2/3/4 has functional variation such as amplification, activating mutation or fusion;
10. Measurable disease according to RECIST version 1.1 or only bone metastasis;
11. Adequate hematological, hepatic function;
12. Doppler ultrasound: left ventricular ejection fraction (LVEF) ≥50%.

Exclusion Criteria:

1. Have used Fulvestrant or its analogues;
2. History of other primary malignancy;
3. Allergic to the ingredients of Anlotinib Hydrochloride Capsules;
4. Previously received targeted drug therapy for FGFR;
5. Received chemotherapy within 4 weeks before enrollment;
6. Received endocrine therapy within 2 weeks before enrollment;
7. Patients with currently symptomatic brain or meningeal metastasis;
8. Concomitant diseases/conditions that is not controllable, and any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the patient's participation in this study;
9. Patients who cannot accept drugs orally;
10. Any other situation that the investigator judges cannot be enrolled in the study.

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: Fulvestrant plus Anlotinib; Each participant receives fulvestrant combined with anlotinib.	Drug: Fulvestrant plus Anlotinib; Each patient receives Fulvestrant (500mg delivered by intramuscular injection every 4 weeks) plus Anlotinib(20mg taken orally for 14 days and stop for 7 days in one cycle)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical benefit rate (CBR)	Response and progression will be evaluated using RECIST 1.1. Evaluation will occur every 3 months till progression or termination of the study. CBR is defined as ratio of participants who have stable disease for over 24 weeks.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The quality of life	Using EORTC (European Organization for Research and Treatment of Cancer) QLQ-BR23 scale. The minimum and maximum values are 0 and 100, respectively. Higher scores mean better outcome.	1 year
Objective response rate (ORR)	The proportion of best overall response of either complete or partial response.	1 year
Overall survival (OS)	Time from the date of treatment to the date of death.	3 years
Number of Participants with Adverse Events	Number of participants with adverse events related to the treatment.	1 year
Progression free survival (PFS)	Time from the date of treatment to the date of tumor progression	1 year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): June 16, 2021
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: June 16, 2021
• First Submitted That Met QC Criteria: June 16, 2021
• First Posted (Actual): June 23, 2021

Study Record Updates

• Last Update Posted (Actual): June 23, 2021
• Last Update Submitted That Met QC Criteria: June 16, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant
• Other Study ID Numbers: SYSU005

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