GB491 Combined With Fulvestrant for HR+ HER2- Locally Advanced or Metastatic Breast Cancer

Locally Advanced or Metastatic Breast Cancer Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Phase III Clinical Trial of GB491 Combined With Fulvestrant in Subjects With HR+, HER2- Locally Advanced or Metastatic Breast Cancer Who Have Progressed on Prior Endocrine Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05054751
• Other study ID #: GB491-004
• Status: Recruiting
• Phase: Phase 3
• Start date: September 10, 2021
• Est. completion date: January 31, 2024

Study information

• Verified date: August 2021
• Source: Genor Biopharma Co., Ltd.
• Contact: Shawn YU, MD
• Phone: 18600332657
• Email: shawn.yu[@]genorbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

GB491-004 is a multicenter, randomized, double-blind, placebo-controlled Phase III study to evaluate the efficacy and safety of GB491 in combination with fulvestrant in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 270
• Est. completion date: January 31, 2024
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Females or males of 18 years of age or older at study screening

2. Histologically or cytologically confirmed locally advanced or advanced metastatic breast cancer that is not amenable to curative surgical resection or radiation therapy

3. The subject has been diagnosed with ER-positive breast cancer in the local laboratory

4. Subject has HER2-negative breast cancer in the local laboratory

5. Menopausal status is not limited (including Premenopausal/perimenopausal/postmenopausal state)

6. According to RECIST V1.1, the patient has at least one measurable lesion that has not been irradiated by radiotherapy and can be evaluated by CT/MRI; If only bone metastases are present, there must be at least one osteolytic bone lesion that can be evaluated by CT/MRI

7. ECOG performance status of 0 or 1

8. Adequate organ and marrow function.

Exclusion Criteria:

1. Previous treatment with fulvestrant, everolimus and any other CDK4/6 inhibitors

2. Subjects with known hypersensitivity to any component of GB491 or Fulvestrant

3. Known active, uncontrolled, or symptomatic central nervous system metastasis, carcinomatous meningitis, or clinically manifested leptomeningeal disease, cerebral edema, spinal compression or/and tumor progressive growth

4. Visceral crisis

5. Patients with skin lesion only and radiographically non-measurable at baseline

6. Persistent toxicities (CTCAE Grade >2) caused by previous anticancer therapy, excluding alopecia

7. Patients who have been on bisphosphonates and denosumab therapy at a stable dose for less than 14 days prior to randomization

8. Patients who have received limited field radiotherapy in 2 weeks or extended field radiotherapy in 4 weeks before randomization or radiation with more than 30% of the bone marrow

9. Subjects use drugs or fruits containing strong inducers or inhibitors of CYP3A4/5, or drugs with narrow therapeutic window that are mainly metabolized by CYP3A4/5 in 14 days before randomization

10. Patients with long-term systematic use of corticosteroids

11. Any severe and/or uncontrollable medical conditions

12. Patients with severely impaired lung function

13. Known history of HIV infection or history of HIV seropositivity

14. Subjects have significant hepatic disease

15. Coagulation abnormalities

16. Subjects with a history of other primary malignancies, except for non-melanoma skin cancer and cervical cancer in situ disease-free status = 3 years

17. Lactating women

Related Conditions & MeSH terms

• Breast Neoplasms
• Locally Advanced or Metastatic Breast Cancer

Intervention

Drug:
• GB491+ Fulvestrant
GB491: The dose of GB491 is 150 mg, which should be taken with a meal and taken twice daily at approximately the same time each day, approximately 12 hours apart. Fulvestrant: Intramuscular injection of flurvexine 500mg on day 1 and day 15 of the first cycle, and flurvexine 500mg on day 1 of the second and subsequent cycles Flurvexine 500mg should be given slowly (1-2 minutes per injection) on both sides of the buttocks, once 250 mg on each side.
• Placebo+Fulvestrant
Placebo: The dose of Placebo is 150 mg, which should be taken with a meal and taken twice daily at approximately the same time each day, approximately 12 hours apart. Fulvestrant: Intramuscular injection of flurvexine 500mg on day 1 and day 15 of the first cycle, and flurvexine 500mg on day 1 of the second and subsequent cycles Flurvexine 500mg should be given slowly (1-2 minutes per injection) on both sides of the buttocks, once 250 mg on each side.

Locations

Country	Name	City	State
China	Beijing Chaoyang Hospital of Capital Medical University	Beijing	Beijing
China	Beijing Tiantan Hospital , Capital Medical University	Beijing	Beijing
China	Cancer hospital Chinese Academy of Medical Sciences	Beijing	Beijing
China	Chinese PLA General Hospital	Beijing	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui
China	Bethune First Hospital Of Jilin University	Changchun	Jillin
China	Jilin Cancer Hospital	Changchun	Jilin
China	The Second Hospital of Jilin University	Changchun	Jilin
China	West China School of Medicine	Chengdu	Sichuan
China	Chognqing University Three Gorges Hospital	Chongqing	Chongqing
China	Chongqing University Cancer Hospital	Chongqing	Chongqing
China	The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	The First people's hospital of Foshan	Foshan	Guangdong
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Guangdong provincial TCM hospital	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	Harbin Medcial Univercity cancer hospital	Haerbin	Heilongjiang
China	Hainan General Hospital	Haikou	Hainan
China	The Second Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Anhui Provincial Cancer Hospital	Hefei	Anhui
China	The Second Hospital of Anhui Medical University	Hefei	Anhui
China	The Affiliated hospital of Inner Mongolia Medical University	Hohhot	Inner Mongolia
China	Central Hospital Affiliated to Shandong First Medical University	Jinan	Shandong
China	Shandong Cancer Hospital	Jinan	Shandong
China	Shandong Provincial Hospital	Jinan	Shandong
China	Shandong Provincial Qianfoshan Hospital	Jinan	Shandong
China	Affiliated hospital of Jining Medical University	Jining	Shandong
China	The Third Affiliated Hospital of Kunming Medical University	Kunming	Yunnan
China	Liaocheng People's Hospital	Liaocheng	Shandong
China	Meizhou People's Hospital	Meizhou	Guangdong
China	Jiangxi Provincial Hospital	Nanchang	Jiangxi
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	Hainan Third People's Hospital	Sanya	Hainan
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai
China	Liaoning Cancer hospital & Institute	Shenyang	Liaoning
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	Cancer Hospital Chinese Academy of Medical Sciences,Shenzhen Center Shenzhen Cancer Hospital	Shenzhen	Guangdong
China	Affiliated hospital of Hebei University	Shijiazhuang	Hebei
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Taian City Central Hospital	Taian	Shandong
China	The first hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin
China	Affiliated Cancer Hospital of Xinjiang Medical University	Urumqi	Xinjiang
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Renmin Hospital of Wuhan University	Wuhan	Hubei
China	Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Hubei
China	First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	Yantai Yuhuangding Hospital	Yantai	Shandong
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Genor Biopharma Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS by BICR.	To assess the progression free survial (PFS), which is assessed by BICR.	Approximately 1.5 years
Secondary	PFS by PI	To assess the progression free survial (PFS), which is assessed by PI.	Approximately 1.5 years
Secondary	OS	To assess the overall survival (OS)	Approximately 3 years
Secondary	ORR	To assess the objective response rate (ORR)	Approximately 1.5 years
Secondary	DOR	To assess the duration of response	Approximately 1.5 years
Secondary	DCR	To assess the disease control rate	Approximately 1.5 years
Secondary	CBR	To assess the clinical benefit rate by BICR	Approximately 1.5 years
Secondary	SAE	To assess the incidence of SAE by Graded according to the National Cancer Institute (NCI CTCAE)	Approximately 3 years
Secondary	AE	To assess the incidence of AE by Graded according to the National Cancer Institute (NCI CTCAE)	Approximately 3 years
Secondary	TEAE	To assess the incidence of TEAE by Graded according to the National Cancer Institute (NCI CTCAE)	Approximately 3 years
Secondary	Cmax	To evaluate the Cmax of GB491 and its metabolites G1T30	On Day15 of Cycle 1 and Day 1 of Cycle 2-4 (each cycle is 28 days)
Secondary	Tmax	To evaluate the Tmax of GB491 and its metabolites G1T30	On Day15 of Cycle 1 and Day 1 of Cycle 2-4 (each cycle is 28 days)
Secondary	AUC	To evaluate the AUC of GB491 and its metabolites G1T30	On Day15 of Cycle 1 and Day 1 of Cycle 2-4 (each cycle is 28 days)