Gastric Cancer
Conditions
Brief summary
The aim of this study is to observe the efficacy and safety of immume checkpoint inhibitor PD-1 SHR1210 combined with Trastuzumab , Oxaliplatin and Capecitabine for Neoadjuvant Therapy of locally advanced resectable gastric and gastroesophageal junction adenocarcinoma.
Detailed description
This study is a prospective, one-arm, phase II clinical study to evaluate the safety and efficacy of SHR-1210 in combination with trastuzumab plus oxaliplatin and capecitabine for HER2-positive locally advanced resectable gastric adenocarcinoma and gastroesophageal junction adenocarcinoma during the perioperative treatment.
Interventions
DRUGSHR-1210 Combined With Trastuzumab , Oxaliplatin and Capecitabine
1. Neoadjuvant chemotherapy： SHR-1210 (200mg, d1, q3w) + trastuzumab ( 8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks) + capecitabine (1000mg/m2 bid d2-15, q3w) + Oxaliplatin (130mg/m2, d2, q3w)；4cycle 2. postoperative adjuvant chemotherapy： Capecitabine (1000mg/m2 bid d1-14, q3w) + oxaliplatin (130mg/m2, d1, q3w)；The total number of chemotherapy cycles is 8 cycles.
Sponsors
Henan Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Signed the informed consent form 2. 18-75 years old 3. Pathologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma (cT4 or / and N+M0, MDT believes that perioperative treatment is required): 1. No peritoneal metastasis in CT 2. evaluated as a resectable lesion. Note: Whether there is a distant metastasis should be confirmed by CT or MR scan. If bone metastasis is suspected, a bone scan should be performed. If there is suspected peritoneal metastasis, a laparoscopy should be performed. If brain metastasis is suspected, CT or MR examination should be performed. 4. Have not received cytotoxic chemotherapy or targeted therapy and local tumor resection 5. HER2 immunohistochemistry 3+ and fluorescence in situ hybridization showed significant amplification 6. ECOG≤1 7. Tumor specimens that can be used to detect PD-L1 and MSI status can be provided. Detection of PD-L1 and MSI will be performed after enrollment. This test requires patients to provide paraffin-embedded biopsy specimens. 8. White blood cells ≥ 4×109/L, platelets without blood transfusion ≥ 100×109/L, absolute neutrophil count (ANC) ≥ 1.5×109/L without granulocyte stimulating factor, hemoglobin ≥ 90 g/L 9. bilirubin ≤ 1.5 times the upper limit of normal value, cereal grass and alanine aminotransferase ≤ 2.5ULN. If there is liver metastasis, the grass and alanine aminotransferase ≤ 5ULN. 10. serum creatinine ≤ 1.5ULN, or GFR \> 45 ml / min 11. serum albumin ≥ 25 g / L (2.5 g / dL) 12. INR or APTT ≤ 1.5 ULN 13. Hepatitis B surface antigen positive patients need to detect hepatitis B DNA virus quantitative detection, only patients below the upper limit of normal detection can be enrolled, and long-term use ofanti-hepatitis B virus drugs
Exclusion criteria
1. Allergic to any test drug and its excipients, or have a history of severe allergies, or a contraindication to test drugs 2. Have a history of autoimmune disease or be active 3. Previously received allogeneic bone marrow transplantation or organ transplantation 4. Congenital pulmonary fibrosis, drug-induced pneumonia, organizing pneumonia, or CT-confirmed active pneumonia 5. HIV test positive 6. Active hepatitis B or hepatitis C 7. Active tuberculosis 8. Uncontrolled cancer pain 9. A live attenuated vaccine is injected within 4 weeks before the start of the study, or it is expected that a live attenuated vaccine will be injected within 5 months after the trial or the end of the trial. 10. Previous use of immunotherapy, including CTLA4, anti-PD-1, or anti-PDL1 mAb 11. Systemic application of glucocorticoids or immunosuppressants within 2 weeks prior to the start of the trial. Inhaled corticosteroids and mineralocorticoids are allowed 12. Hormone use contraindications。 13. severe cardiovascular disease, myocardial infection or cerebrovascular accident, arrhythmia, unstable angina within 3 months before the start of the test 14. Uncontrollable increase in blood pressure or elevated blood sugar 15. History of other malignant tumors 5 years ago, except for cervical cancer in situ, non-melanoma skin cancer or stage I uterine cancer 16. Known central nervous system metastasis 17. ≥ NCI CTCAE Level 2 Peripheral Neuropathy 18. serum albumin is less than 2.5 g/dL 19. uncontrollable or symptomatic hypercalcemia 20. Infections requiring antibiotics within 14 days prior to the start of the test 21. chronic enteritis 22. clinically significant active gastrointestinal bleeding 23. Non-diagnostic surgery within 4 weeks prior to the start of the trial 24 There is evidence of the need to limit any other disease using the test drug 25\. Participate in other tests within 30 days before the start of the test, or plan to participate in other tests during the test. Accept other experimental drugs within 28 days before the start of the test 26. Women who are pregnant or lactating, or women who are planning to become pregnant within 5 months of the end of treatment. Women of childbearing age are required to undergo a blood pregnancy test within 7 days prior to the start of the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pathological complete response (pCR) rate | up to 2 year | the rate of no residual tumor cells in both the excised gastric cancer and lymph node (ypT0N0) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | up to 2 year | Defined as the proportion of patients with a documented complete response, and partial response (CR \+ PR ) |
| Overall survival(OS) | up to 2 year | From date of randomization until the date of death from any cause |
| safety | up to 2 year | adverse events in patients during the neoadjuvant treatment phase |
| Disease Free Survival（DFS） | up to 2 year | The time from the start of randomization to the first tumor recurrence/metastasis or the death of the subject for any reason |
Countries
China
Outcome results
None listed