A Study of RC48-ADC Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer With or Without Liver Metastases
A Randomized, Controlled, Multi-center Phase II Clinical Study to Evaluate the Efficacy and Safety of Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Conjugate for Injection in the Treatment of HER2-positive Locally Advanced or Metastatic Breast Cancer and Phase III Clinical Study to Evaluate the Efficacy and Safety of Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Conjugate for Injection in the Treatment of HER2-positive Advanced Breast With Liver Metastases
1 other identifier
interventional
301
1 country
67
Brief Summary
This is a randomized, open, parallel-controlled, multicenter, phase II/III, seamless design clinical trial to compare the efficacy and safety of RC48-ADC with capecitabine + lapatinib in locally advanced or metastatic human epidermal growth factor receptor 2 (HER2) positive breast cancer and HER2-positive advanced breast cancer with liver metastasis.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Apr 2018
Longer than P75 for phase_2
67 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 8, 2018
CompletedFirst Posted
Study publicly available on registry
April 18, 2018
CompletedStudy Start
First participant enrolled
April 24, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2024
CompletedFebruary 20, 2024
November 1, 2023
6.3 years
April 8, 2018
February 18, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free Survival (PFS) as Assessed by an IRC
Tumor response was assessed by an IRC according to RECIST v1.1.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Secondary Outcomes (6)
Progression-free Survival (PFS) as Assessed by Investigator
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Objective Response Rate （ORR）
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Duration of Objective Response (DOR)
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Clinical Benefit Rate （CBR）
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Time to Treatment Failure
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
- +1 more secondary outcomes
Study Arms (2)
RC48-ADC
EXPERIMENTALParticipants will receive RC48-ADC 2.0 mg/kg intravenous (IV) infusion each 14-day treatment cycle until disease progression (PD) (as assessed by the investigator), unmanageable toxicity, or study termination.
Lapatinib + Capecitabine
ACTIVE COMPARATORParticipants will receive lapatinib 1250 mg orally once daily during each 21-day cycle + capecitabine 2000 mg/m\^2 orally daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Interventions
Capecitabine 2000 mg/m\^2 orally daily on Days 1-14 of each 21-day treatment cycle.
Eligibility Criteria
You may qualify if:
- Voluntarily agree to participate in the study and sign the informed consent form.
- Subjects aged 18 - 70 years (inclusive), and the subject who have not reached the age of 71 years old will be considered to be ≤ 70 years of age.
- Expected survival ≥ 12 weeks.
- ECOG PS score 0 or 1.
- Female subjects should be surgically sterilized or in post-menopausal status, or agree to use at least one medically accepted contraceptive methods (such as intrauterine device, contraceptive drug or condom) during study treatment period and for up to 6 months after the study treatment is completed, and the blood pregnancy test must be negative within 7 days prior to study enrollment, and they must not be lactating. For male subjects: all the subjects should be surgically sterilized or agree to use one of the medically approved contraceptive methods during the study treatment period and for an additional of 6 months after the end of the study treatment period.
- Able to understand study requirements, willing and able to comply with study protocol and follow-up procedures.
- With Adequate Organ Function
- Bone marrow function:
- Hemoglobin ≥ 9 g/dL; Absolute neutrophil count ≥ 1.5×109/L; Platelets ≥ 100 × 109/L;
- Liver function (based on the normal values specified by study site):
- Serum total bilirubin ≤ 1.5 × the upper limit of normal (ULN); Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤ 2.5 × ULN in the absence of liver metastases, while ALT, AST and ALP ≤ 5 × ULN in the presence of liver metastases;
- Renal function (based on the normal values specified by study site):
- Serum creatinine ≤ 1.5 × ULN, or creatinine clearance (CrCl) ≥ 60 mL/min as calculated by Cockcroft-Gault formula, or 24-hour urine Crcl ≥ 60 mL/min;
- Cardiac function:
- New York Heart Association (NYHA) classification \< Grade III; Left ventricular ejection fraction ≥ 50%; Tumor Related Criteria
- +7 more criteria
You may not qualify if:
- Use of investigational drugs within 4 weeks prior to study treatment;
- Have received major surgeries within 4 weeks prior to study treatment and have not recovered yet;
- Have received a live vaccine inoculation within 4 weeks prior to the start of study drug administration or was scheduled to receive any vaccine during the study;
- Have experienced arterial/venous thromboembolic events, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism within 1 year prior to the initiation of study treatment;
- Suffering uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, interstitial lung disease, cirrhosis, etc.;
- Currently suffering from active infections requiring systemic treatment;
- With history of active tuberculosis;
- With positive HIV test result;
- Patients with active hepatitis B or C (HBsAg positive and HBV DNA positive; HCVAb positive);
- Presence of effusion in the third space (including massive hydrothorax or ascites) that cannot be controlled by drainage or other methods;
- With known hypersensitivity or delayed-type hypersensitivity to certain components of RC48-ADC, capecitabine, lapatinib or similar drugs;
- With pre-existing gastrointestinal disorders that may affect absorption, such as ileus, ulcerative colitis, chronic diarrhea, inability to swallow, and other conditions that may affect drug administration and absorption;
- With known psychiatric disorders or drug abuse disorders that might have an impact on compliance with protocol requirements;
- Have any other diseases, metabolic disorders, abnormal physical examination findings or abnormal laboratory test results, which, judged by the investigator, are reasonably to suspect a disease or condition as a contraindication of the study drug, or may interfere the interpretation of the study results in the future, or that put the patient at a high risk;
- Women who are pregnant or during lactation period or women/men with childbearing plans;
- +48 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (67)
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100021, China
Liaoning Cancer Hospital & Institute
Shenyang, Liaoning, China
The First Hospital of China Medical University
Shenyang, Liaoning, China
An Yang Cancer Hospital
Anyang, China
Beijing Luhe Hospital
Beijing, China
Peking University People's Hospital
Beijing, China
The First Affiliated Hospital of Bengbu Medical College
Bengbu, China
Bin Zhou No.1 People's Hospital
Binzhou, China
Jilin Cancer Hospital
Changchun, China
The First Hospital Jilin University
Changchun, China
The First Hospital of Jilin University
Changchun, China
Hunan Cancer Hospital
Changsha, China
The Second Xiyang Hospital of Central South University
Changsha, China
Xiangya Hospital Central South University
Changsha, China
Heping Hospital Affiliated to Changzhi Medical College
Changzhi, China
Affiliated Hospital of Chengde Medical University
Chengde, China
West China Hospital,Sichuan University
Chengdu, China
Chongqing University Three gorges Hospital
Chongqing, China
The Southwest Hospital of AMU
Chongqing, China
The Second Hospital of Dalian Medical University
Dalian, China
Fujian Cancer Hospital
Fuzhou, China
Guangdong Provincial People's Hospital
Guangzhou, China
Sun Yat-Sen Memorial Hospital
Guangzhou, China
The Affiliated Tumor Hospital of Guangzhou Medical University
Guangzhou, China
Guizhou Cancer Hospital
Guiyang, China
The First Affiliated Hospital of Medical School of Zhejiang University
Hangzhou, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, China
Zhejiang Cancer Hospital
Hangzhou, China
Harbin Medical University Cancer Hospital
Ha’erbin, China
Anhui Cancer Hospital
Hefei, China
Anhui Province Hospital
Hefei, China
The First Affiliated Hospital of Anhui Medical University
Hefei, China
Qilu Hospital of Shandong University
Jinan, China
The First People's Hospital of Jining
Jining, China
Yunnan Cancer Hospital
Kunming, China
Linyi Cancer Hospital
Linyi, China
The First Affiliated Hospital of Henan University of Science & Technology
Luoyang, China
Jiangsu Cancer Hospital
Nanjing, China
The Affiliated Tumor Hospital of Guangxi Medical University
Nanning, China
The Second People's Hospital of Neijiang
Neijiang, China
Hospital of Qingdao University
Qingdao, China
Fudan University Shanghai Cancer Center
Shanghai, China
Shanghai Changhai Hospital
Shanghai, China
Shanghai Ruijin Hospital
Shanghai, China
Cancer Hospital of Shantou University Medical College
Shantou, China
Yue Bei People's Hospital
Shaoguan, China
The Fourth Hospital of Hebei Medical University
Shijiazhuang, China
Shanxi Bethune Hospital
Taiyuan, China
Shanxi Cancer Hospital
Taiyuan, China
Taizhou Enze Medical Center
Taizhou, China
Tai'an City Central Hospital
Tai’an, China
Tianjin Cancer Hospitial
Tianjin, China
Weihai Municipal Hospital
Weihai, China
Hubei Cancer Hospital
Wuhan, China
Tongji Medical College of HUST
Wuhan, China
Wuhan Union Hospital
Wuhan, China
The First Affiliated Hospital of the Fourth Military University of P.L.A.
Xi'an, China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, China
Xing Tai People's Hospital
Xingtai, China
The First Affiliated Hospital of Xinxiang Medical University
Xinxiang, China
The Affiliated Hospital of Xuzhou Medical University
Xuzhou, China
Xuzhou Central Hospital
Xuzhou, China
Yanbian University Hospital
Yanbian, China
Yantai Yuhuangding Hospital
Yantai, China
Yuncheng Central Hospital
Yuncheng, China
Henan Cancer Hospital
Zhengzhou, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 8, 2018
First Posted
April 18, 2018
Study Start
April 24, 2018
Primary Completion
July 31, 2024
Study Completion
December 31, 2024
Last Updated
February 20, 2024
Record last verified: 2023-11
Data Sharing
- IPD Sharing
- Will not share