Clinical trial NCT03950271: SHR-1210 Combined With Trastuzumab , Oxaliplatin and Capecitabine for Neoadjuvant Therapy of Gastric Adenocarcinoma/Gastroesophageal Junction Adenocarcinoma
Official title: Phase II Clinical Study of PD1 Antibody (SHR-1210) Combined With Trastuzumab, Oxaliplatin and Capecitabine for Neoadjuvant Therapy of Gastric Adenocarcinoma/Gastroesophageal Junction Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Gastric Cancer
Lead sponsor: Henan Cancer Hospital
Sponsor class: OTHER_GOV
First posted: 2019-05-15
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: pathological complete response (pCR) rate
timeFrame: up to 2 year
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: up to 2 year
measure: Overall survival(OS)
timeFrame: up to 2 year
measure: safety
timeFrame: up to 2 year
measure: Disease Free Survival（DFS）
timeFrame: up to 2 year
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
Study officials:
affiliation: Henan Cancer Hospital
name: Suxia Luo
role: PRINCIPAL_INVESTIGATOR
References: