Clinical trial NCT05744687: Phase II/III Study of SPH4336 Combined With Letrozole vs Placebo Combined With Letrozole in First-line Treatment of Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Locally Advanced or Metastatic Breast Cancer
Lead sponsor: Shanghai Pharmaceuticals Holding Co., Ltd
Sponsor class: INDUSTRY
First posted: 2023-02-27
Enrollment: 374
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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.

Primary outcomes:
measure: response rate (ORR)
timeFrame: Approximately 3years
measure: Progression-free survival (PFS)
timeFrame: Approximately 3years
Secondary outcomes:
measure: Cmax
timeFrame: Approximately 3years
measure: Tmax
timeFrame: Approximately 3years
measure: Disease control rate (DCR)
timeFrame: Approximately 3years
measure: Duration of remission (DOR)
timeFrame: Approximately 3years
measure: Overall Survival (OS)
timeFrame: Approximately 8years
measure: Incidence of Adverse event
timeFrame: Approximately 3years
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: Affiliated Cancer Hospital, Sun Yat-sen University
state: Guangdong
city: Guiyang
country: China
facility: The Affiliated Cancer Hospital of Guizhou Medical University
state: Guizhou
city: Anyang
country: China
facility: AnYang Tumor Hospital
state: Henan
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Pingxiang
country: China
facility: Pingxiang People's Hospital
state: Jiangxi
city: Chang chun
country: China
facility: The Second Norman Bethune Hospital of Jilin Univer
state: Jilin
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Beijing
country: China
facility: Peking University Cancer Hospital
Study officials:
References: