Back to results

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

Primary Purpose

Breast Cancer

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Fulvestrant plus Anlotinib

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Voluntarily sign the informed consent form;
18-75 years old;
Women in any menstrual state, premenopausal or perimenopausal patients need to receive luteinizing hormone releasing hormone(LHRH) analogue;
Eastern Cooperative Oncology Group (ECOG) score [0-1] points;
The expected survival period is ≥12 weeks;
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);
Inoperable or recurrent/metastatic breast cancer patients with aromatase inhibitor treatment failure;
In the state of disease progression before enrollment;
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;
Measurable disease according to RECIST version 1.1 or only bone metastasis;
Adequate hematological, hepatic function;
Doppler ultrasound: left ventricular ejection fraction (LVEF) ≥50%.

Exclusion Criteria:

Have used Fulvestrant or its analogues;
History of other primary malignancy;
Allergic to the ingredients of Anlotinib Hydrochloride Capsules;
Previously received targeted drug therapy for FGFR;
Received chemotherapy within 4 weeks before enrollment;
Received endocrine therapy within 2 weeks before enrollment;
Patients with currently symptomatic brain or meningeal metastasis;
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;
Patients who cannot accept drugs orally;
Any other situation that the investigator judges cannot be enrolled in the study.

Sites / Locations

Sun Yat-sen University Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fulvestrant plus Anlotinib

Arm Description

Each participant receives fulvestrant combined with anlotinib.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Progression free survival (PFS)

Time from the date of treatment to the date of tumor progression

Objective response rate (ORR)

The proportion of best overall response of either complete or partial response.

Overall survival (OS)

Time from the date of treatment to the date of death.

Number of Participants with Adverse Events

Number of participants with adverse events related to the treatment.

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.

Full Information

NCT ID

NCT04936295

First Posted

June 16, 2021

Last Updated

June 16, 2021

Sponsor

Sun Yat-sen University

1. Study Identification

Unique Protocol Identification Number

NCT04936295

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2021

Overall Recruitment Status

Recruiting

Study Start Date

June 16, 2021 (Anticipated)

Primary Completion Date

June 1, 2023 (Anticipated)

Study Completion Date

June 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

61 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Fulvestrant plus Anlotinib

Arm Type

Experimental

Arm Description

Each participant receives fulvestrant combined with anlotinib.

Intervention Type

Drug

Intervention Name(s)

Fulvestrant plus Anlotinib

Intervention Description

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)

Primary Outcome Measure Information:

Title

Clinical benefit rate (CBR)

Description

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

Progression free survival (PFS)

Description

Time from the date of treatment to the date of tumor progression

Time Frame

1 year

Title

Objective response rate (ORR)

Description

The proportion of best overall response of either complete or partial response.

Time Frame

1 year

Title

Overall survival (OS)

Description

Time from the date of treatment to the date of death.

Time Frame

3 years

Title

Number of Participants with Adverse Events

Description

Number of participants with adverse events related to the treatment.

Time Frame

1 year

Title

The quality of life

Description

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.

Time Frame

1 year

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Voluntarily sign the informed consent form; 18-75 years old; Women in any menstrual state, premenopausal or perimenopausal patients need to receive luteinizing hormone releasing hormone(LHRH) analogue; Eastern Cooperative Oncology Group (ECOG) score [0-1] points; The expected survival period is ≥12 weeks; 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); Inoperable or recurrent/metastatic breast cancer patients with aromatase inhibitor treatment failure; In the state of disease progression before enrollment; 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; Measurable disease according to RECIST version 1.1 or only bone metastasis; Adequate hematological, hepatic function; Doppler ultrasound: left ventricular ejection fraction (LVEF) ≥50%. Exclusion Criteria: Have used Fulvestrant or its analogues; History of other primary malignancy; Allergic to the ingredients of Anlotinib Hydrochloride Capsules; Previously received targeted drug therapy for FGFR; Received chemotherapy within 4 weeks before enrollment; Received endocrine therapy within 2 weeks before enrollment; Patients with currently symptomatic brain or meningeal metastasis; 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; Patients who cannot accept drugs orally; Any other situation that the investigator judges cannot be enrolled in the study.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Fei Xu, MD

Phone

+86-13711277870

xufei@sysucc.org.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Kuikui Jiang, MD

Phone

+86-15210589011

jiangkk@sysucc.org.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Fei Xu, MD

Organizational Affiliation

Sun Yat-sen University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sun Yat-sen University Cancer Center

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Fei Xu, MD

Phone

+86-13711277870

xufei@sysucc.org.cn

First Name & Middle Initial & Last Name & Degree

Fei Xu, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs