A Study Evaluating the Combination of Encorafenib and Cetuximab Versus Irinotecan/Cetuximab or Infusional 5-fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab in Chinese Patients With BRAF V600E Mutant Metastatic Colorectal Cancer.
- Conditions
- Metastatic Colorectal CancerBRAF V600E
- Interventions
- Registration Number
- NCT05004350
- Lead Sponsor
- Pierre Fabre Medicament
- Brief Summary
Encorafenib is currently being developed (with or without binimetinib), in combination with cetuximab, for the treatment of adult patients with B-RAF proto-oncogene, serine/threonine kinase V600E mutant (BRAF V600E) metastatic colorectal cancer (mCRC), who have received prior systemic therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 107
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Encorafenib and cetuximab Encorafenib Safety Lead-in (SLI) phase: 28 day cycles of encorafenib once daily (QD) 300 mg (4 x 75 mg oral capsule) and cetuximab 400 mg/m² initial dose (120-minute infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly Randomized (Phase II) phase: 28 day cycles of encorafenib once daily (QD) 300 mg (4 x 75 mg oral capsule) and cetuximab 400 mg/m² initial dose (120-minute infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly Irinotecan and cetuximab or FOLFIRI and cetuximab FOLFIRI Randomized (Phase II) phase: Either irinotecan and cetuximab or FOLFIRI and cetuximab in 28 day cycles. Irinotecan and cetuximab: * irinotecan 180 mg/m² (90-minute intravenous infusion or to study site standards) every 2 weeks and * cetuximab 400 mg/m² initial dose (120-minute intravenous infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly OR FOLFIRI and cetuximab: * irinotecan 180 mg/m² (90-minute intravenous infusion or to study site standards) every 2 weeks * Folinic acid 400 mg/m² (120-minute infusion or to study site standards) or maximal dose tolerated in a prior regimen every 2 weeks * 5-FU 400 mg/m² initial dose bolus (not to exceed 15 minutes), then 1200 mg/m²/day × 2 days (total 2400 mg/m² over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen every 2 weeks and * cetuximab 400 mg/m² initial dose (120-minute intravenous infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly Irinotecan and cetuximab or FOLFIRI and cetuximab Encorafenib Randomized (Phase II) phase: Either irinotecan and cetuximab or FOLFIRI and cetuximab in 28 day cycles. Irinotecan and cetuximab: * irinotecan 180 mg/m² (90-minute intravenous infusion or to study site standards) every 2 weeks and * cetuximab 400 mg/m² initial dose (120-minute intravenous infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly OR FOLFIRI and cetuximab: * irinotecan 180 mg/m² (90-minute intravenous infusion or to study site standards) every 2 weeks * Folinic acid 400 mg/m² (120-minute infusion or to study site standards) or maximal dose tolerated in a prior regimen every 2 weeks * 5-FU 400 mg/m² initial dose bolus (not to exceed 15 minutes), then 1200 mg/m²/day × 2 days (total 2400 mg/m² over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen every 2 weeks and * cetuximab 400 mg/m² initial dose (120-minute intravenous infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly Encorafenib and cetuximab Cetuximab Safety Lead-in (SLI) phase: 28 day cycles of encorafenib once daily (QD) 300 mg (4 x 75 mg oral capsule) and cetuximab 400 mg/m² initial dose (120-minute infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly Randomized (Phase II) phase: 28 day cycles of encorafenib once daily (QD) 300 mg (4 x 75 mg oral capsule) and cetuximab 400 mg/m² initial dose (120-minute infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly Irinotecan and cetuximab or FOLFIRI and cetuximab Cetuximab Randomized (Phase II) phase: Either irinotecan and cetuximab or FOLFIRI and cetuximab in 28 day cycles. Irinotecan and cetuximab: * irinotecan 180 mg/m² (90-minute intravenous infusion or to study site standards) every 2 weeks and * cetuximab 400 mg/m² initial dose (120-minute intravenous infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly OR FOLFIRI and cetuximab: * irinotecan 180 mg/m² (90-minute intravenous infusion or to study site standards) every 2 weeks * Folinic acid 400 mg/m² (120-minute infusion or to study site standards) or maximal dose tolerated in a prior regimen every 2 weeks * 5-FU 400 mg/m² initial dose bolus (not to exceed 15 minutes), then 1200 mg/m²/day × 2 days (total 2400 mg/m² over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen every 2 weeks and * cetuximab 400 mg/m² initial dose (120-minute intravenous infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly
- Primary Outcome Measures
Name Time Method Safety Lead-in Phase: Incidence of Dose Limiting Toxicities (DLTs) during the DLT-evaluation period (which is the first 28 days after the first dose of study intervention in the SLI) Day 1 to Day 28 Randomized Phase 2: Progression-free Survival (PFS) by Blinded (to treatment received) Independent Central Review (BICR) Day 1 through to study completion, approximately from 12 to 29 months Defined as the time from the date of randomization to the earliest documented disease progression as determined by BICR assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1., or death due to any cause
- Secondary Outcome Measures
Name Time Method Safety Lead-in Phase: Type and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Informed consent through to study completion, approximately from 18 to 35 months Safety Lead-in Phase: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of physical examinations Day 1 through to study completion, approximately from 18 to 35 months Standard physical examinations on cardiovascular, respiratory, gastrointestinal, dermatological, ophthalmological and neurological systems will be performed and will be evaluated based on normal/abnormal and clinical significance observations. Number of participants with TEAEs related to abnormal or clinical significance observations to the physical examinations after the start of study drug will be reported.
Safety Lead-in Phase: Incidence of dose interruptions, dose modifications and discontinuations due to adverse events (AEs) Day 1 until end of treatment, approximately 1 year Safety Lead-in Phase: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes in vital signs from baseline of vital sign examinations. Day 1 through to study completion, approximately from 18 to 35 months Clinically notable elevated values: Systolic blood pressure (BP): ≥ 160 mmHg and an increase ≥ 20 mmHg from baseline; Diastolic BP: ≥ 100 mmHg and an increase ≥ 15 mmHg from baseline; Heart rate : ≥ 120 beats/min (bpm) with increase from baseline of ≥ 15 bpm; Weight (kg) increase from baseline of ≥ 10%; Body temperature(°C) ≥ 37.5°C). Clinically notable low values: Systolic BP: ≤ 90 mmHg with decrease from baseline of ≥ 20 mmHg; Diastolic BP: ≤ 50 mmHg with decrease from baseline of ≥ 15 mmHg; Heart rate: ≤ 50 bpm with decrease from baseline of ≥ 15 bpm; Weight: ≥ 20% decrease from baseline; Body temperature \[°C\]: ≤ 36 °C. Number of participants with TEAEs related to notable changes to the vital signs after the start of study drug will be reported.
Safety Lead-in Phase: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of 12-lead electrocardiograms (ECGs) Day 1 through to study completion, approximately from 18 to 35 months 12-lead ECGs will be obtained using an internationally recognized 12-lead cardiograph. Clinically notable ECG values: QT (ms) and QT interval (ms) corrected for heart rate using Fridericia's formula (QTcF) intervals (ms) : increase from baseline \> 30 ms; increase from baseline \> 60 ms, new \> 450 ms, new \> 480 ms, new \> 500 ms. Heart rate (beats/min) : increase from baseline \> 25% to a value \> 100 bpm, decrease from baseline \> 25% and to a value \< 50 bpm. Number of participants with TEAEs related to abnormal or notable changes to ECG parameters after the start of study drug will be reported.
Safety Lead-in Phase: Incidence of treatment-emergent adverse events (TEAEs) related to notable changes in clinical safety laboratory parameters from baseline. Day 1 through to study completion, approximately from 18 to 35 months Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.03 were graded from Grades 1 to 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Clinically notable shift is defined as a worsening from baseline by at least 2 grades, or to grade 3 or above.
Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab maximum concentration (Cmax) in Chinese participants Day 1 of Cycles 1 and 2; Each cycle = 28 days Randomized Phase 2: Overall Response Rate (ORR) Day 1 through to study completion, approximately from 12 to 29 months Overall response rate (for confirmed and unconfirmed responses) defined as the proportion of participants with a confirmed (resp. unconfirmed) best overall response of either complete response or partial response, as determined by Blinded (to treatment received) Independent Central Review (BICR) and investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Safety Lead-in Phase: Incidence of development of of keratoacanthoma and/or squamous cell carcinoma and new primary melanoma by dermatological examinations Screening (Day -28 to -1) through to study completion, approximately from 18 to 35 months This is to monitor for the possible development of keratoacanthoma and/or squamous cell carcinoma and new primary melanoma, as these have been reported to occur with selective BRAF inhibitor treatment. This assessment will be performed at screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7...), the end of treatment visit and the 30-day safety follow up visit.
Safety Lead-in Phase: Performance status assessment using the Eastern Co-operative Oncology Group (ECOG) performance status scale Screening (Day -28 to -1) through to study completion, approximately from 18 to 35 months Scale with a range from 0 to 5 with lower score mean a lower functional impairment, 5 corresponding to death
Safety Lead-in Phase: Plasma concentrations of encorafenib Day 1 of Cycles 1 and 2; Each cycle = 28 days Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab area under curve (AUC) in Chinese participants Day 1 of Cycles 1 and 2; Each cycle = 28 days Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib minimum concentration (Cmin) in Chinese participants Day 1 of Cycles 1 and 2; Each cycle = 28 days Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab minimum concentration (Cmin) in Chinese participants Day 1 of Cycles 1 and 2; Each cycle = 28 days Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib maximum concentration (Cmax) in Chinese participants Day 1 of Cycles 1 and 2; Each cycle = 28 days Safety Lead-in Phase: Serum concentrations of cetuximab Day 1 of Cycles 1 and 2; Each cycle = 28 days Safety Lead-in Phase; Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib area under curve (AUC) in Chinese participants Day 1 of Cycles 1 and 2; Each cycle = 28 days Safety Lead-in Phase: Objective response rate (ORR) Day 1 through to study completion, approximately from 18 to 35 months Objective response rate (ORR) defined as the proportion of participants with a best overall best response of either complete response (CR) or partial response (PR) as determined by Blinded (to treatment received) Independent Central Review (BICR) and investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Safety Lead-in Phase: Duration of Response (DOR) (months); defined for responders complete response (CR) or partial response (PR) only, is duration of time from the date of the first documented response to the earliest date of disease progression Day 1 through to study completion, approximately from 18 to 35 months Duration of response, defined as the time from first documented response (complete response or partial response) to the earliest date of disease progression as determined by Blinded (to treatment received) Independent Central Review (BICR) and investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, or death due to underlying disease.
Randomized Phase 2: Progression-free survival (PFS) Day 1 through to study completion, approximately from 12 to 29 months Progression-free survival defined as the interval of time between the date of randomization to the earliest date of disease progression, as determined by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause.
Randomized Phase 2: Duration of Response (DOR) Day 1 through to study completion, approximately from 12 to 29 months Duration of response defined as the time from the date of the first documented response (complete response or partial response) to the earliest date of disease progression, as determined by Blinded (to treatment received) Independent Central Review (BICR) and investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause
Randomized Phase 2: Disease control rate (DCR) Day 1 through to study completion, approximately from 12 to 29 months Disease control rate (DCR), defined as the proportion of participants with a best overall response of either complete response, partial response or stable disease (SD), as determined by Blinded (to treatment received) Independent Central Review (BICR) and investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Randomized Phase 2: Time to Response (TTR) Day 1 through to study completion, approximately from 12 to 29 months Time to Response (for confirmed and unconfirmed responses) is defined as the time between date of randomization until first documented response of complete response (CR) or partial response (PR).
Randomized Phase 2: Overall Survival (OS) Day 1 through to study completion, approximately from 12 to 29 months Overall survival is defined as time from randomization until date of death due to any cause
Randomized Phase 2: Type and severity of adverse events (AEs) and serious adverse events (SAEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Informed consent date through to study completion, approximately from 12 to 29 months Randomized Phase 2: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of physical examinations Day 1 through to study completion, approximately from 12 to 29 months Standard physical examinations on cardiovascular, respiratory, gastrointestinal, dermatological, ophthalmological and neurological systems will be performed and will be evaluated based on normal/abnormal and clinical significance observations. Number of participants with TEAEs related to abnormal or clinical significance observations to the physical examinations after the start of study drug will be reported
Randomized Phase 2: Incidence of treatment-emergent adverse events (TEAEs) related to notable changes in vital signs from baseline. Day 1 through to study completion, approximately from 12 to 29 months Clinically notable elevated values: Systolic blood pressure (BP): ≥ 160 mmHg and an increase ≥ 20 mmHg from baseline; Diastolic BP: ≥ 100 mmHg and an increase ≥ 15 mmHg from baseline; Heart rate : ≥ 120 beats/min (bpm) with increase from baseline of ≥ 15 bpm; Weight (kg) increase from baseline of ≥ 10%; Body temperature(°C) ≥ 37.5°C). Clinically notable low values: Systolic BP: ≤ 90 mmHg with decrease from baseline of ≥ 20 mmHg; Diastolic BP: ≤ 50 mmHg with decrease from baseline of ≥ 15 mmHg; Heart rate: ≤ 50 bpm with decrease from baseline of ≥ 15 bpm; Weight: ≥ 20% decrease from baseline; Body temperature \[°C\]: ≤ 36 °C. Number of participants with TEAEs related to notable changes to the vital signs after the start of study drug will be reported.
Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes to electrocardiogram evaluations from baseline Day 1 through to study completion, approximately from 12 to 29 months 12-lead ECGs will be obtained using an internationally recognized 12-lead cardiograph. Clinically notable ECG values: QT (ms) and QT interval (ms) corrected for heart rate using Fridericia's formula (QTcF) intervals (ms): increase from baseline \> 30 ms; increase from baseline \> 60 ms, new \> 450 ms, new \> 480 ms, new \> 500 ms; Heart rate (beats/min): increase from baseline \> 25% to a value \> 100 bpm, decrease from baseline \> 25% and to a value \< 50 bpm. Number of participants with TEAEs related to abnormal or notable changes to ECG parameters after the start of study drug will be reported.
Randomized Phase 2: Incidence of treatment-emergent adverse events (TEAEs) related to notable changes in clinical safety laboratory parameters from baseline. Day 1 through to study completion, approximately from 12 to 29 months Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.03 were graded from Grades 1 to 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Clinically notable shift is defined as a worsening from baseline by at least 2 grades, or to grade 3 or above.
Randomized Phase 2: Incidence of development of keratoacanthoma and/or squamous cell carcinoma and new primary melanoma by dermatological examinations Day 1 through to study completion, approximately from 12 to 29 months This is to monitor for the possible development of keratoacanthoma and/or squamous cell carcinoma and new primary melanoma, as these have been reported to occur with selective BRAF inhibitor treatment. This assessment will be performed at screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7...), the end of treatment visit and the 30-day safety follow up visit.
Randomized Phase 2: To determine the performance status using the Eastern Co-operative Oncology Group (ECOG) performance status scale. Day 1 through to study completion, approximately from 12 to 29 months Scale with a range from 0 to 5 with lower score mean a lower functional impairment, 5 corresponding to death
Randomized Phase 2: To determine if there is any change from baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients (EORTC QLQ-C30) questionnaire scores Day 1 through to study completion, approximately from 12 to 29 months EORTC QLQ-C30 consist of nine multi-item scales: five functional scales (physical, role, cognitive, emotional and social); three symptom scales (fatigue, pain, nausea and vomiting); and a global health and Quality of Life (QoL) scale. Each scale in the questionnaire will be scored (0 to 100). High scores represents a high health/quality of life
Randomized Phase 2: To determine if there is any change from baseline in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) questionnaire scores. Day 1 through to study completion, approximately from 12 to 29 months EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (VAS). The descriptive system has five dimension (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), each is rated according to a five-point verbal rating scale (VRS): 1. no problems, 2. slight problems, 3. moderate problems, 4. severe problems and 5. extreme problems) and translated into a five-digit number that describes the participant's health state.
Randomized Phase 2: To determine if there is any change from baseline in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) questionnaire scores Day 1 through to study completion, approximately from 12 to 29 months FACT-C is a validated quality of life questionnaire for patient reported outcome assessment. FACT-C consists of 36 items, presented on a five-point Likert scale, in four domains of well-being (physical, emotional, social and functional) and the Colorectal Cancer Subscale. Higher score reflects a better quality of life.
Randomized Phase 2: To determine if there is any changes in the Patient Global Impression of Change (PGIC) questionnaire scores. Day 1 through to study completion, approximately from 12 to 29 months PGIC will ask participants to evaluate their CRC symptoms since starting study intervention according to a seven-point verbal rating scale (VRS): 1. very much improved, 2. much improved, 3. minimally improved, 4. no change, 5. minimally worse, 6. much worse, 7. very much worse
Randomized Phase 2: Plasma concentrations of encorafenib Day 1 of Cycles 1 and 2; Each cycle = 28 days Randomized Phase 2: Serum concentrations of cetuximab Day 1 of Cycles 1 and 2; Each cycle = 28 days Randomized Phase 2; Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib area under curve (AUC) in Chinese participants Day 1 of Cycles 1 and 2; Each cycle = 28 days Randomized Phase 2: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab area under curve (AUC) in Chinese participants Day 1 of Cycles 1 and 2; Each cycle = 28 days Randomized Phase 2: Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib minimum concentration (Cmin) in Chinese participants Day 1 of Cycles 1 and 2; Each cycle = 28 days Randomized Phase 2: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab minimum concentration (Cmin) in Chinese participants Day 1 of Cycles 1 and 2; Each cycle = 28 days Randomized Phase 2: Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib maximum concentration (Cmax) in Chinese participants Day 1 of Cycles 1 and 2; Each cycle = 28 days Randomized Phase 2: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab maximum concentration (Cmax) in Chinese participants Day 1 of Cycles 1 and 2; Each cycle = 28 days Randomized Phase 2: Population pharmacokinetic (PK) analysis using the ARRAY 818 302 study PK data Day 1 through to study completion, approximately from 12 to 29 months
Trial Locations
- Locations (34)
Fujian Medical University - Fujian Provincial Cancer Hospital
🇨🇳Fuzhou, Fujian, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
First Affiliated Hospital of Gannan Medical University
🇨🇳Ganzhou, Jiangxi, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
The First Affiliated Hospital of Jinzhou Medical University
🇨🇳Jinzhou, Liaoning, China
Xinhua Hospital Affilliated to Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Shanghai East Hospital, Tongji University
🇨🇳Shanghai, Shanghai, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, Shanghai, China
The First People's Hospital of Changzhou
🇨🇳Changzhou, Jiangsu, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Peking University Shenzhen Hospital
🇨🇳Shenzhen, Guangdong, China
Shaanxi Provincial People's Hospital
🇨🇳Xi'an, Shaanxi, China
The First Affiliated Hospital - Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Xiangya Hospital Central South University
🇨🇳Changsha, Hunan, China
Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
The First People's Hospital of Foshan
🇨🇳Foshan, Guangdong, China
Cancer Hospital Affiliated to Shantou University Medical College
🇨🇳Shantou, Guangdong, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China
The Second Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
The Second People's Hospital of Neijiang
🇨🇳Neijiang, Sichuan, China
Liaoning Cancer Hospital & Institute
🇨🇳Shenyang, Liaoning, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, Tianjin, China
Sir Run Run Shaw Hospital - Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, Fujian, China
The Affiliated Hospital of Hebei University
🇨🇳Baoding, Hebei, China
Union Hospital Tongji medical college Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Zhongnan Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Cancer Center of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
The Sixth Affiliated Hospital Sun Yat-Sen University
🇨🇳Guangzhou, Guangdong, China
Huashan Hospital Fudan University
🇨🇳Shanghai, Shanghai, China