To Evaluate the Efficacy and Safety of TQB3616 in Combination With Fulvestrant Versus Placebo in Combination With Fulvestrant in Previously Untreated Hormone-receptor (HR)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Advanced Breast Cancer
- Conditions
- HR-positive, HER2-negative Breast Neoplasms
- Interventions
- Registration Number
- NCT05365178
- Lead Sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Brief Summary
A randomized, double-blind, parallel-controlled, multicenter trial design was used in this study. Subjects who meet the criteria will be randomly divided into 2:1 groups to receive TBQ3616 capsule combined with Fulvestrant injection (experimental group) or placebo capsule combined with fulvestrant (control group). A total of 428 subjects were required.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 432
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Subjects voluntarily participate in this study and sign informed consent with good compliance;
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Age: 18-75 years (when signing the informed consent); an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Is expected to survive more than 3 months;
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Postmenopausal or premenopausal/perimenopausal women；
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Patients with HR-positive or HER2-negative breast cancer confirmed by pathological examination with evidence of local lesion recurrence or distant metastasis, not suitable for the surgery or radiotherapy for the purpose of cure, and there are no clinical indications of chemotherapy；
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Have a measurable lesion (RECIST (Response Evaluation Criteria In Solid Tumors) 1.1 criteria), or have only bone metastases；
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The main organs function well and meet the following standards：
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Routine blood examination should meet the following criteria: (No blood transfusion and no hematopoietic stimulation drugs within 7 days before screening)
- Hemoglobin (HB) ≥100 g/L;
- Absolute value of neutrophils (NEUT) ≥ 1.5×109/L;
- Platelet count (PLT) ≥ 90 ×109/L.
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Biochemical blood tests shall meet the following criteria：
- Total bilirubin (TBIL) ≤ 1.5 times normal upper limit (ULN);
- Alanine transferase (ALT) and aspartate transferase (AST) ≤ 2.5×ULN; ALT and AST≤ 3×ULN for patients with liver metastasis;
- Serum creatinine (Cr) ≤ 1.5×ULN, or creatinine clearance (Ccr) ≥ 60 mL /min；
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Coagulation function tests shall meet the following criteria：
(a) Prothrombin time (PT), activated partial thrombin time (APTT), international standardized
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Color doppler echocardiography: Left ventricular ejection fraction (LVEF) ≥50%；
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Female subjects within reproductive age should agree to use contraceptive methods (such as intrauterine devices, birth control pills or condoms) from participating the study to 6 months after the end of the study; Serum pregnancy test result should be negative within 7 days prior to study enrollment and must be non-lactating subjects.
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Associated diseases and history：
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The presence or current co-occurrence of other malignant tumors within 5 years, except ured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor infiltrating basal membrane)];
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Multiple factors affecting oral and drug absorption (such as inability to swallow, post-gastrointestinal resection, ulcerative colitis, symptomatic/inflammatory bowel disease, chronic diarrhea and intestinal obstruction);
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Patients with a history of severe pneumonia such as interstitial lung disease;
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Unrelieved toxicity higher than GRADE 1 Common Terminology Criteria for Adverse Events (CTCAE) due to any previous anti-tumor treatment, hair loss is not included;
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Major surgery or significant traumatic injury within 28 days prior to randomization;
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Long-term unhealed wounds, ulcers or fractures;
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Occurrence of arteriovenous/venous thrombosis events within 6 months, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.;
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History of psychotropic drug abuse and can't get rid of it or with mental disorders;
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Subject with any severe and/or uncontrolled disease, including：
- Arrhythmias requiring treatment with grade≥2 myocardial ischemia, myocardial infarction, and congestive heart failure (NYHA(New York Heart Association) classification) within 6 months prior to study enrollment (including qtc≥480ms during screening period); And uncontrolled high blood pressure;
- Active or uncontrolled severe infection (≥CTCAE grade 2 infection) or unexplained fever > 38.5℃ within 28 days prior to randomization;
- Decompensated cirrhosis (Child-Pugh liver function score B or C), active hepatitis ;
- Patients with renal failure requiring hemodialysis or peritoneal dialysis;
- A history of immunodeficiency, including HIV ( Human Immunodeficiency Virus) positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation or hematopoietic stem cell transplantation;
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Tumor-related symptoms and treatment；
- Visceral crisis exists;
- Severe bone injury due to bone metastasis of tumor;
- Received radiotherapy (except palliative radiotherapy for non-target lesions) and other anti-tumor therapies (the washout period was calculated from the end of the last treatment) within 2 weeks prior to randomization;
- Prior medical treatment with fulvestrant, everolimus or CDK4/6 inhibitor;
- The presence of clinically uncontrolled pleural, ascites and pericardial effusion requiring repeated drainage or medical intervention (14 days prior to randomization);
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Known allergy to fulvestrant, Luteal Hormone Releasing Hormone (LHRH) agonists (e.g. Goserelin), TQB3616/ placebo or any supplement;
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History of live attenuated vaccine vaccination within 28 days prior to randomization or planned live attenuated vaccine vaccination during the study period;
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Participated in clinical trials of other antitumor drugs within 4 weeks pior to randomization;
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With other serious physical or mental diseases or abnormal laboratory tests that may increase the risk of study participation or interfere with the study results, or unsuitable for the study for other reasons considered by investigators.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TQB3616 capsule + Fulvestrant injection TQB3616 capsule TQB3616 capsule: 180mg was given orally with meals or within 2 hours after meals, once a day， every 28 days for a cycle. Fulvestrant injection: 500mg intramuscular injection was administered on day 1, every 28 days for a cycle, for the first cycle, was administered on day 1 and day 15 TQB3616 capsule + Fulvestrant injection Fulvestrant injection TQB3616 capsule: 180mg was given orally with meals or within 2 hours after meals, once a day， every 28 days for a cycle. Fulvestrant injection: 500mg intramuscular injection was administered on day 1, every 28 days for a cycle, for the first cycle, was administered on day 1 and day 15 Placebo capsule + Fulvestrant injection Placebo Placebo capsules: 0mg was given orally with meals or within 2 hours after meals, once a day, every 28 days for a cycle. Fulvestrant injection: 500mg intramuscular injection was administered on day 1, every 28 days for a cycle, for the first cycle, was administered on day 1 and day 15 Placebo capsule + Fulvestrant injection Fulvestrant injection Placebo capsules: 0mg was given orally with meals or within 2 hours after meals, once a day, every 28 days for a cycle. Fulvestrant injection: 500mg intramuscular injection was administered on day 1, every 28 days for a cycle, for the first cycle, was administered on day 1 and day 15
- Primary Outcome Measures
Name Time Method Progression-free survival as assessed by the investigator Baseline up to progressive disease (PD)/die, about 25.8 months The time from enrollment to the date of the first documentation of objective progression of disease or death due to any cause, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) by independent imaging assessment Baseline up to PD/die, about 25.8 months The time from enrollment to the date of the first documentation of objective progression of disease or death due to any cause, whichever occurs first.
Objective Response Rate (ORR) Baseline to CR/PR，about 1 year Duration of Overall Response (DOR) CR/PR assessment, up to PD/die, about 20 months The time from the date of participants with a first overall response defined as complete response (CR) or partial response (PR) to the date of the first documentation of objective progression of disease or death due to any cause, whichever occurs first.
The European Organization for Research and Treatment of Cancer Quality of Life questionnaire Baseline to the end of the study, about 3 years Sense of satisfaction, life quality of participants since the enrollment of the study
Incidence of adverse events (AEs), serious adverse events (SAEs) and treatment-related adverse events (TEAEs). Baseline to the end of the study, about 3 years The occurrence of all adverse events (AEs), serious adverse events (SAEs) and treatment-related adverse events (TEAEs).
Overall survival Baseline up to die, about 36months Overall survival was defined as the time from randomization to death from any cause.
3-Year Overall Survival (OS) Baseline to 3 years The percentage of participants of survival above 3 years
Clinical Benefit Rate(CBR) Baseline to CR/PR/SD，about 1 year Calculated as the percentage of participants with best overall response of CR, PR, stable disease (SD) and Non-CR/Non-progressive disease (PD).
Trial Locations
- Locations (88)
The First Affiliated Hospital of Wannan Medical College
🇨🇳Wuhu, Anhui, China
Fujian Provincial Cancer Hospital
🇨🇳Fuzhou, Fujian, China
Gansu Provincial Cancer Hospital
🇨🇳Lanzhou, Gansu, China
Lanzhou University Second Hospital
🇨🇳Lanzhou, Gansu, China
Yue Bei People's Hospital
🇨🇳Shaoguan, Guangdong, China
Zhongshan City People's Hospital
🇨🇳Zhongshan, Guangdong, China
The Second Affiliated Hospital of Guilin Medical University
🇨🇳Guilin, Guangxi, China
The Affiliated Hospital of Hebei University
🇨🇳Baoding, Hebei, China
Affiliated Cancer Hospital of Harbin Medical University
🇨🇳Harbin, Heilongjiang, China
The Second Affiliated Hospital of Harbin Medical University
🇨🇳Harbin, Heilongjiang, China
Nanyang Central Hospital
🇨🇳Nanyang, Henan, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Yichang Central People's Hospital
🇨🇳Yichang, Hubei, China
The First People's Hospital of Changde
🇨🇳Changde, Hunan, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
Nanjing Drum Tower Hospital
🇨🇳Nanjing, Jiangsu, China
Affiliated Hospital of Nantong University
🇨🇳Nantong, Jiangsu, China
The Affiliated Hospital of Xuzhou Medical University
🇨🇳Xuzhou, Jiangsu, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Second Hospital of Jilin University
🇨🇳Changchun, Jilin, China
The Second Hosptial of DaLian Medical University
🇨🇳Dalian, Liaoning, China
Affiliated Zhongshan Hospital of Dalian University
🇨🇳Dalian, Liaoning, China
The First Affiliated Hospital of Jinzhou Medical University
🇨🇳Jinzhou, Liaoning, China
Inner Mongolia Autonomous Region Cancer Hospital
🇨🇳Hohhot, Neimenggu, China
The Affilliate Hospital of Inner Mongolia Medical Univercity
🇨🇳Hohhot, Neimenggu, China
Liaoning Cancer Hospital & Institute
🇨🇳Shenyang, Liaoning, China
Qinghai University affiliated hospital
🇨🇳Xining, Qinghai, China
Binzhou Medical College Affiliated Hospital
🇨🇳Binzhou, Shandong, China
Shandong Cancer Hospital
🇨🇳Jinan, Shandong, China
Affiliated Hospital of Jining Medical University
🇨🇳Jining, Shandong, China
General Hospital of Ningxia Medical
🇨🇳Yinchuan, Ningxia, China
Second Affiliated Hospital of PLA Air Force Military Medical
🇨🇳Xi'an, Shaanxi, China
The First Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, Shaanxi, China
Linyin Cancer Hospital
🇨🇳Linyi, Shandong, China
Qingdao University Affiliated Hospital
🇨🇳Qingdao, Shandong, China
Weifang Hospital of Traditional Chinese Midicine
🇨🇳Weifang, Shandong, China
Yantai Yantai Mountain hospital
🇨🇳Yantai, Shandong, China
Zibo Central Hospital
🇨🇳Zibo, Shandong, China
Huadong Hospital
🇨🇳Shanghai, Shanghai, China
Shanghai Oriental Hospital
🇨🇳Shanghai, Shanghai, China
Shanghai Changhai Hospital
🇨🇳Shanghai, Shanghai, China
Chinese People's Liberation Army Western Theater General Hospital
🇨🇳Chengdu, Sichuan, China
The Affiliated Hospital of Southwest Medical University
🇨🇳Luzhou, Sichuan, China
Tianjin Medical University Cancer Hospital Konggang Hospital
🇨🇳Tianjin, Tianjin, China
Yunnan Cancel Hospital
🇨🇳Kunming, Yunan, China
Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medcine
🇨🇳Hangzhou, Zhejiang, China
Cancer Hospital affiliated to Xinjiang Medical University
🇨🇳Urumqi, Xinjiang, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
The First Affiliated Hospital of Bengbu Medical College
🇨🇳Bengbu, Anhui, China
The Southwest Hospital of AMU
🇨🇳Chongqing, Chongqing, China
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
Jieyang People's Hospital
🇨🇳Jieyang, Guangdong, China
The First Affiliated Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Suining Central Hospital
🇨🇳Suining, Sichuan, China
Tianjin Medical University Cancer Hospital
🇨🇳Tianjin, Tianjin, China
Xi'an International Medical Center Hospital
🇨🇳Xi'an, Shaanxi, China
Chongqing University Cancer Hospital
🇨🇳Chongqing, Chongqing, China
Gansu Wuwei Tumour Hospital
🇨🇳Wuwei, Gansu, China
Nanfang Hospital Southern Medical University
🇨🇳Guangzhou, Guangdong, China
Maoming people's hospital
🇨🇳Maoming, Guangdong, China
The Third Affiliated Hospital of Sun Yat-Sen University
🇨🇳Guangzhou, Guangdong, China
ShenZhen People's Hospital
🇨🇳Shenzhen, Guangdong, China
PeKing University ShenZhen Hosipital
🇨🇳Shenzhen, Guangdong, China
The Fifth Affiliated Hospital of Sun Yat-Sen University
🇨🇳Zhuhai, Guangdong, China
Yulin First People's Hospital
🇨🇳Yulin, Guangxi, China
Hebei Cangzhou Hospital of Integrated Traditional Chinese
🇨🇳Cangzhou, Hebei, China
Cangzhou Central Hospital
🇨🇳Cangzhou, Hebei, China
Affiliated Hospital of Chengde Medical University
🇨🇳Chengde, Hebei, China
Hebei Petro China Central Hospital
🇨🇳Langfang, Hebei, China
The Fourth Hospital of Hebei Medical University
🇨🇳Shijiazhuang, Hebei, China
Jiamusi Cancer Hospital
🇨🇳Jiamusi, Heilongjiang, China
Luoyang Central Hospital
🇨🇳Luoyang, Henan, China
Huai'an First People's Hospital
🇨🇳Huai'an, Jiangsu, China
Changzhou Cancer Hospital
🇨🇳Changzhou, Jiangsu, China
Jiangsu province hospital
🇨🇳Nanjing, Jiangsu, China
Jilin Cancer Hospital
🇨🇳Changchun, Jilin, China
The First Affiliated Hospital of Gannan Medical University
🇨🇳Ganzhou, Jiangxi, China
The Third Hospital of Nanchang
🇨🇳Nanchang, Jiangxi, China
Affiliated Hospital of Chifeng University
🇨🇳Chifeng, Neimenggu, China
First Affiliated University Hospital of PLA Air Force Military Medical
🇨🇳Xi'an, Shaanxi, China
Shanxi Cancer Hospital
🇨🇳Taiyuan, Shanxi, China
Changzhi People's Hospital
🇨🇳Changzhi, Shanxi, China
The Second Affiliated Hospital Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Peking University First Hospital
🇨🇳Beijing, Beijing, China