Gastric or Esophagogastric Junction Adenocarcinoma Clinical Trial
Official title:
An International, Multicenter, Randomized, Double-blind, Phase III Clinical Study to Evaluate the Efficacy and Safety of Toripalimab Injection Combined With Postoperative Adjuvant Chemotherapy Versus Placebo Combined With Postoperative Adjuvant Chemotherapy in Patients With Gastric or Gastroesophageal Junction Adenocarcinoma After Radical Gastrectomy
This international, multicenter, randomized, double-blind phase III study intends to recruit 680 patients who have received radical gastrectomy (R0 resection, D2 or more extended lymphadenectomy) with postoperative pathological stage II or III (AJCC Cancer Staging Manual, 8th Edition) gastric or EGJ adenocarcinoma to evaluate the efficacy and safety of JS001 combined with postoperative adjuvant chemotherapy versus placebo combined with postoperative adjuvant chemotherapy.
| Status | Recruiting |
| Enrollment | 680 |
| Est. completion date | July 31, 2028 |
| Est. primary completion date | March 31, 2026 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 75 Years |
| Eligibility | INCLUSION CRITERIA 1. Age 18-75 years. 2. No residual tumor (R0) after D2 or greater lymphadenectomy through laparotomy. 3. According to the definition of the 8th edition of the AJCC Cancer Staging Manual, patients with gastric adenocarcinoma confirmed by histopathology, pathological stage II (T4aN0M0) and stage III, including gastroesophageal junction adenocarcinoma (GEJ) patients. 4. ECOG performance status 0-1. 5. No metastasis or recurrence as radiologically confirmed. 6. Patients must have adequate organ function as assessed in the laboratory tests. 7. Patients must provide informed consent for this study, and sign the written informed consent form voluntarily before the initiation of the study, and are willing and able to comply with the scheduled visits, treatment plan, laboratory examinations and other study procedures in the study. 8. Female patients of childbearing age must take a serum pregnancy test within 7 days before randomization with negative results, and agree to adopt reliable and effective contraceptive methods during the study. 4.2 EXCLUSION CRITERIA 1. Previous use of non-surgical therapy for gastric adenocarcinoma. 2. Having liver, peritoneal or distant metastasis. 3. Inability to take the drug orally. 4. Having postoperative complications that are not relieved at the time of randomization. 5. Uncontrolled pericardial effusion or pleural effusion which required invasive treatment, and grade II or above peritoneal effusion (diagnosed clinically) present at screening. 6. Presence of contraindicated chemotherapeutic drugs in this study and failure to receive the adjuvant therapeutic regimen in any group specified in the protocol. 7. Having received any surgery not for gastric adenocarcinoma requiring general anesthesia within 28 days prior to randomization. 8. Having malignant tumors other than gastric adenocarcinoma within 5 years before randomization. 9. Active autoimmune disorders requiring systemic treatment. 10. Patients with immunodeficiency or receiving long-term systemic steroid therapy. 11. Concurrent diverticulitis or symptomatic gastrointestinal ulcer disease. 12. Patients who are receiving or requiring anticoagulant therapy. 13. Patients with serious cardiovascular and cerebrovascular diseases. 14. Diabetes mellitus that is not effectively controlled. 15. Active infections requiring treatment. 16. =Grade 2 peripheral neuropathy. 17. Patients with active tuberculosis or having received anti-tuberculosis therapy within one year prior to randomization. 18. Patients currently having interstitial lung disease or having a history of interstitial lung disease. 19. Hepatitis B, known positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb), and HBV DNA=1000cps/ml; hepatitis C, positive HCV RNA or RNA =1000cps/ml. 20. Human immunodeficiency virus (HIV) antibody positive. 21. Vaccination of any live vaccine within 4 weeks before randomization. 22. Previous allogeneic bone marrow transplantation or solid organ transplantation. 23. Previous treatment targeting PD-1 receptor or its ligand PD-L1 or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) receptor; 24. Previous history of serious allergy to monoclonal antibody or other biological preparations. 25. Having participated in other interventional clinical studies within 28 weeks before randomization. 26. Having clinically significant underlying medical disease that may affect administration of study drug or compliance to the protocol, as judged by investigators. 27. Other patients who are considered by investigators as inappropriate for enrollment. |
| Country | Name | City | State |
|---|---|---|---|
| China | Beijing Cancer hospital | Beijing | Beijing |
| China | Beijing Friendship Hospital, Capital Medical University | Beijing | Beijing |
| China | Beijing Hospital | Beijing | Beijing |
| China | Chinese PLA General Hospital | Beijing | Beijing |
| China | Peking University People's hospital | Beijing | Beijing |
| China | The First Affiliated Hospital of Bengbu Medical College | Bengbu | Anhui |
| China | China-Japan Union Hospital of Jilin University | Changchun | Jilin |
| China | The First Hospital of Jilin University | Changchun | Jilin |
| China | Hunan Cancer Hopital | Changsha | Hunan |
| China | Xiangya Hospital Central South University | Changsha | Hunan |
| China | The First People's Hospital of Changzhou | Changzhou | Jiangsu |
| China | SiChuan Cancer Hospital | Chengdu | Sichuan |
| China | The Peple's Hospital of Chizhou | Chizhou | Anhui |
| China | The first affiliated hospital of chongqing medical universit | Chongqing | Chongqing |
| China | The First People's Hospital of Foshan | Foshan | Guangdong |
| China | Fujian Provincial Cancer Hospital | Fuzhou | Fujian |
| China | Affiliated Cancer Hospital and Institute of Ghuangzhou Medical University | Guangzhou | Guangdong |
| China | Guandong General Hospital | Guangzhou | Guandong |
| China | Nanfang Hospital of Southern Medical University | Guangzhou | Guangdong |
| China | The First Affiliated Hospital of Sun yat-sen University | Guangzhou | Guangdong |
| China | Zhujiang Hospital of Southern Medical University | Guangzhou | Guandong |
| China | The 2ed Affiliated Hospital of Harbin Medical University | Ha'erbin | Heilongjiang |
| China | The first affiliated hospital of Zhejiang medical university | Hangzhou | Zhejiang |
| China | The Second Affiliated Hospital of Zhejiang University School of Medicine | Hangzhou | Zhejiang |
| China | Harbin Medical University Cancer Hospital | Harbin | Heilongjiang |
| China | The First Hospital of Jiaxing | Jiaxing | Zhejiang |
| China | Jinan Central Hospital | Jinan | Shangdong |
| China | Shandong Cancer Hospital | Jinan | Shandong |
| China | Shandong Provincial Hospital | Jinan | Shangdong |
| China | Affiliated Hospital of Jining Medical University | Jining | Shangdong |
| China | Gansu Provincial Cancer Hospital | Lanzhou | Gansu |
| China | Gansu Provincial People's Hospital | Lanzhou | Gansu |
| China | Lanzhou University Second Hospital | Lanzhou | Gansu |
| China | The first Hospital of Lanzhou University | Lanzhou | Gansu |
| China | Linyi Cancer Hospital | Linyi | Shandong |
| China | The First Affiliated Hospital of Henan University of science and Technology | Luoyang | Henan |
| China | Jiangmen Central Hospital | Nanchang | Jiangxi |
| China | The first Affiliated Hospital of Nanchang University | Nanchang | Jiangxi |
| China | The Second Affiliated Hospital of Nanchang University | Nanchang | Jiangxi |
| China | Jiangsu cancer hospital | Nanjing | Jiangsu |
| China | Jiangsu Province Hospital | Nanjing | Jiangsu |
| China | Guangxi Medical University Affiliated Tumor Hospital | Nanning | Guangxi |
| China | Nantong Tumor Hospital | Nantong | Jiangsu |
| China | Qingdao central medical group | Qingdao | Shandong |
| China | The Affiliated Hospital of Qingdao University | Qingdao | Shandong |
| China | Shanghai General Hospital | Shanghai | Shanghai |
| China | Zhongshan Hospital, Fudan university | Shanghai | Shanghai |
| China | Yuebei People's Hospital | Shaoguan | Guangdong |
| China | The First Hospital of China Medical University | Shengyang | Liaoning |
| China | LiaoNing Cancer Hospital & Institute | Shenyang | Liaoning |
| China | Peking University Shenzhen Hospital | Shenzhen | Guangdong |
| China | Shenzhen People's Hospital | Shenzhen | Guangdong |
| China | The Fourth Hospital of Hebei Medical University | Shijiazhuang | Hebei |
| China | Suining Central Hospital | Suining | Sichuan |
| China | Shanxi Provincial People's Hospital | Taiyuan | Shanxi |
| China | Cancer Hospital affiliated to Xinjiang Medical University | Urumqi | Xinjiang |
| China | The Second Affiliated Hospital of Wenzhou Medical University | Wenzhou | Zhejiang |
| China | Hubei Cancer Hospital | Wuhan | Hubei |
| China | Union Hospital, Tongji Medical College,Huazhong University of Science and Technology | Wuhan | Hubei |
| China | Wuwei Cancer Hospital of Gansu Province | Wuwei | Gansu |
| China | The Second People's Hospital of Wuxi | Wuxi | Jiangsu |
| China | The First Affiliated Hospital of Xiamen University | Xiamen | Fujian |
| China | Tangdu hospital, Air force Military Medical University | Xian | Shanxi |
| China | Xijing hospital, Air force Military Medical University | Xian | Shanxi |
| China | Xiangyang Central Hospital | Xiangyang | Hubei |
| China | Qinghai University Affiliated Hosptial | Xining | Qinghai |
| China | Yichang Central People's Hospital | Yichang | Hubei |
| China | General Hospital of Ningxia Medical University | Yinchuan | Ningxia |
| China | Henan cancer hospital | Zhengzhou | Henan |
| China | The First Affiliated Hospital of Zhengzhou University | Zhengzhou | Henan |
| China | Affiliated Hospital of Zunyi Medical University | Zunyi | Guizhou |
| Lead Sponsor | Collaborator |
|---|---|
| Shanghai Junshi Bioscience Co., Ltd. |
China,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | DFS evaluated by the BICR based on RECIST v1.1 | To evaluate the disease-free survival (DFS) as per RECIST v1.1 by the blind independent central review (BICR) for toripalimab injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or EGJ adenocarcinoma after radical gastrectomy. | Through study completion, average of 60 months | |
| Secondary | DFS evaluated by the investigator based on RECIST v1.1 | To evaluate the disease-free survival (DFS) evaluated by the investigator for Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy. | Through study completion, average of 60 months | |
| Secondary | DFS rate at 3 years evaluated by the BICR based on RECIST v1.1 | To evaluate the postoperative DFS rate and overall survival (OS) rate at 3 years for Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy. | 36 months | |
| Secondary | DFS rate at 5 years evaluated by the BICR based on RECIST v1.1 | To evaluate the postoperative DFS rate and overall survival (OS) rate at 5 years for Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy. | 60 months | |
| Secondary | OS | To evaluate the OS for Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy. | 5 years | |
| Secondary | Overall survival rate (OS rate) at 3 years and 5 years | To evaluate the postoperative overall survival (OS) rate at 3 for Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy. | 3 years and 5 years | |
| Secondary | Time to local recurrence (TTLR) | To evaluate the time to local recurrence (TTLR) for Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy. | Through study completion, average of 60 months | |
| Secondary | Time to response (TTR) | To evaluate thetime to recurrence (TTR) for Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy. | Through study completion, average of 60 months | |
| Secondary | Incidence and severity of adverse events (AE),clinically significant abnormal changes in vital signs, ECOG scores, physical examination, electrocardiogram (ECG), echocardiography and laboratory examinations | To evaluate the safety of Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy. | Through study completion, average of 60 months | |
| Secondary | To explore the correlation of PD-L1 status, tumor mutation burden (TMB) status, microsatellite status and EBV status with DFS, DFS rate , OS, OS rate at ,TTLR and TTR[efficacy] of adjuvant therapy. | To evaluate the correlation of PD-L1 status, tumor mutation burden (TMB) status, microsatellite status and EBV status with the efficacy of adjuvant therapy. | Within 6 Months after C1D1 | |
| Secondary | To evaluate the potential correlation of the incidence of ADA of Toripalimab Injection (JS001) with incidence and severity of adverse events (AE)[safety] and DFS, DFS rate , OS, OS rate ,TTLR and TTR[efficacy]. | To evaluate the incidence and titer of anti-drug antibody (ADA) of Toripalimab Injection (JS001). | At every other cycle(each cycle is 21 days)up to 17 cycles | |
| Secondary | To evaluate the quality of life in the two groups using the EORTC QLQ-C30 questionnaires | To evaluate the disease-related symptoms and health-related quality of life (HRQoL) in the two groups through the European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life questionnaire (EORTC QLQ-C30) a. The EORTC QLQ-C30 consists of three subscales with 30 questions. The EORTC QLQ-C30 have three subscales in the scale include functioning scales (15 questions), symptom scales (13 questions), and global health status (2 questions). The reliability and validity of Cronbach'a was 0.81-0.94. The functional scale and the global health status , the higher the total score, the better the quality of life; the lower the score in the symptom scale, the better the quality of life. | From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 1 approximately years | |
| Secondary | To evaluate the quality of life in the two groups using the EORTC QLQ-STO22 questionnaires | To evaluate the disease-related symptoms and health-related quality of life (HRQoL) in the two groups through the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Stomach (QLQ-STO22).The EORTC QLQ-STO22 consists of one subscale with 22 questions.The EORTC QLQ-STO22 scale include symptom scales (22 questions) The Cronbach'a was 0.70-0.94.The lower the score in the symptom scale, the better the quality of life. | From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 1 approximately years |