Phase II/III Study of SPH4336 Combined With Letrozole vs Placebo Combined With Letrozole in First-line Treatment of Breast Cancer

Locally Advanced or Metastatic Breast Cancer Clinical Trial

Official title:

Randomized, Double-blind, Placebo-controlled, Phase II/III Study of SPH4336 Combined With Letrozole vs Placebo Combined With Letrozole in First-line Treatment of HR-positive, HER2-negative Locally Advanced or Metastatic Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05744687
• Other study ID #: SPH4336-301
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: April 24, 2023
• Est. completion date: December 16, 2024

Study information

• Verified date: May 2024
• Source: Shanghai Pharmaceuticals Holding Co., Ltd
• Contact: Shusen Wang
• Phone: 0086-020-87343811
• Email: wangshs[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to evaluate the safety and efficacy of SPH4336 combined with letrozole in first-line treatment of locally advanced or metastatic breast cancer

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 374
• Est. completion date: December 16, 2024
• Est. primary completion date: August 18, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Patients who voluntarily participate in the study, completely understand the study, and voluntarily sign the informed consent form (ICF).

2. Female, = 18 and = 75 years of age at the time of signing the ICF.

3. ECOG(Eastern Cooperative Oncology Group) performance status 0 or 1.

4. Life expectancy = 3 months.

5. Patients with locally advanced or metastatic breast cancer who are unable to receive radical surgeries/other local therapies, with hormone receptor positive and human epidermal growth factor receptor 2 negative confirmed by tumor histopathology and molecular pathology.

6. No previous systemetic therapy for locally advanced or metastatic diseases that cannot receive radical surgeries/other local therapies.

7. At least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors.

8. Postmenopausal or premenopausal/perimenopausal female patients. Premenopausal or perimenopausal women should consent to receive goserelin therapy during the study.

9. Laboratory test results before randomization meet the relevant requirements for organ function.

Exclusion Criteria:

1. Prior treatment with any CDK4/6 (Cyclin dependent kinase)inhibitor.

2. Inflammatory breast cancer.

3. Patients unsuitable for endocrine therapy at the investigator's discretion.

4. History of other malignancies within 5 years prior to the start of study treatment.

5. Patients with known central nervous system metastases.

6. Taking anti-tumor traditional Chinese medicines at the time of signing the ICF.

7. Having undergone a surgery within 28 days prior to the start of study treatment, and hasn't yet recovered from adverse reactions of the surgery.

8. History of myocardial infarction, unstable angina pectoris, severe arrhythmia, and symptomatic congestive heart failure before the start of study treatment; NYHA( New York Heart Association) Class =II; QTcF= 470 ms; LVEF(Left Ventricular Ejection Fractions)= 50%.

9. History of ischemic stroke or severe thromboembolic disease before the start of study treatment.

10. Being receiving potent CYP3A4 inhibitors or inducers at the time of signing the ICF.

11. Hepatitis B surface antigen positive and HBV(Hepatitis B Virus) DNA > 2,000 IU/mL or 104 copies/mL; HCV(hepatitis C virus) antibody positive and HCV RNA positive; or known HIV infection.

12. Patients who participated in a clinical trial and received other investigational drugs within 30 days before the start of study treatment.

13. History of severe anaphylactic diseases, history of severe drug allergy, or known allergy to any ingredient of the investigational product.

14. Presence of diseases or conditions that may impact drug administration or gastrointestinal absorption before the start of study treatment, in the opinion of the investigator, makes them an unsuitable candidate for the study.

15. Uncontrolled infections within 2 weeks before the start of study treatment, in the opinion of the investigator, makes them an unsuitable candidate for the study.

16. Pregnant or lactating women.

17. Known history of substance abuse, excessive drinking, or illegal drug addiction; history of confirmed neurological or mental disorders.

18. Presence of other diseases judged by the investigator that the risks of receiving the study treatment outweigh its benefits, or any other reason for which patients are ineligible for the study as assessed by the investigator and the sponsor.

Related Conditions & MeSH terms

• Breast Neoplasms
• Locally Advanced or Metastatic Breast Cancer

Intervention

Drug:
• SPH4336 Tablets 400mg
SPH4336 Tablets :Orally, 400mg once a day; 28 days/cycle Letrozole tablets :Orally, 2.5mg once a day; 28 days/cycle
• SPH4336 Tablets Placebo
SPH4336 Tablets Placebo:Orally,28 days/cycle Letrozole tablets :Orally, 2.5mg once a day; 28 days/cycle

Locations

Country	Name	City	State
China	AnYang Tumor Hospital	Anyang	Henan
China	Peking University Cancer Hospital	Beijing
China	The Second Norman Bethune Hospital of Jilin Univer	Chang chun	Jilin
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Affiliated Cancer Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	The Affiliated Cancer Hospital of Guizhou Medical University	Guiyang	Guizhou
China	The First Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan
China	Pingxiang People's Hospital	Pingxiang	Jiangxi
China	The Second Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Tai'an Central Hospital	Tai'an	Shandong
China	Tianjin Medical University cancer Institute & Hospital	Tianjin
China	Renmin Hospital of Wuhan University Hubei General Hospital	Wuhan	Hubei
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Pharmaceuticals Holding Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	response rate (ORR)	tumor response will be evaluated according to the Response Evaluation Criteria Solid Tumors (RECIST) criteria version 1.1.	Approximately 3years
Primary	Progression-free survival (PFS)	from the start date of study treatment to the date of progression disease or death , whichever occurred first.	Approximately 3years
Secondary	Cmax	PK (Pharmacokinetics) parameters	Approximately 3years
Secondary	Tmax	PK (Pharmacokinetics) parameters	Approximately 3years
Secondary	Disease control rate (DCR)	DCR was defined as the percentage of patients who have achieved complete response, partial response and stable disease.	Approximately 3years
Secondary	Duration of remission (DOR)	DOR was defined for participants who had an objective response as the time from the first occurrence of a documented unconfirmed response to the date of disease progression per RECIST v1.1 or death from any cause.	Approximately 3years
Secondary	Overall Survival (OS)	Determination of the overall survival times of all patients.	Approximately 8years
Secondary	Incidence of Adverse event	Safety and tolerability	Approximately 3years