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出境医 / 临床实验 / SHR-1210 Combined With Trastuzumab , Oxaliplatin and Capecitabine for Neoadjuvant Therapy of Gastric Adenocarcinoma/Gastroesophageal Junction Adenocarcinoma

SHR-1210 Combined With Trastuzumab , Oxaliplatin and Capecitabine for Neoadjuvant Therapy of Gastric Adenocarcinoma/Gastroesophageal Junction Adenocarcinoma

Study Description
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.

Condition or disease Intervention/treatment Phase
Gastric Cancer Drug: SHR-1210 Combined With Trastuzumab , Oxaliplatin and Capecitabine Phase 2

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.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 21, 2020
Estimated Primary Completion Date : December 1, 2020
Estimated Study Completion Date : June 1, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: SHR-1210+ Trastuzumab + Oxaliplatin + Capecitabine
trastuzumab + SHR-1210 + capecitabine + oxaliplatin for neoadjuvant chemotherapy 4-cycle.Then D2 radical surgery. The patients continued to receive capecitabine plus oxaliplatin for adjuvant therapy, and the total number of chemotherapy cycles was 8 cycles.
Drug: SHR-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.

Outcome Measures
Primary Outcome Measures :
  1. Disease Free Survival(DFS) [ Time Frame: 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


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: up to 2 year ]

    Defined as the proportion of patients with a documented complete response, and partial response (CR

    + PR )


  2. Overall survival(OS) [ Time Frame: up to 2 year ]
    From date of randomization until the date of death from any cause

  3. pathological complete response (pCR) rate [ Time Frame: up to 2 year ]
    the rate of no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations

Contacts
Layout table for location contacts
Contact: Ning Li 13526501903 lining97@126.com

Locations
Layout table for location information
China, Henan
Henan Cancer Hospital Recruiting
Zhengzhou, Henan, China, 450008
Contact: Ning Li, PhD    0086-13526501903    lining97@126.com   
Principal Investigator: Ning Li, PhD         
Principal Investigator: Suxia Luo, PhD         
Sponsors and Collaborators
Henan Cancer Hospital
Investigators
Layout table for investigator information
Principal Investigator: Suxia Luo Henan Cancer Hospital
Tracking Information
First Submitted Date  ICMJE May 13, 2019
First Posted Date  ICMJE May 15, 2019
Last Update Posted Date May 29, 2020
Actual Study Start Date  ICMJE January 21, 2020
Estimated Primary Completion Date December 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 13, 2019)
Disease Free Survival(DFS) [ Time Frame: 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2019)
  • Objective Response Rate (ORR) [ Time Frame: up to 2 year ]
    Defined as the proportion of patients with a documented complete response, and partial response (CR + PR )
  • Overall survival(OS) [ Time Frame: up to 2 year ]
    From date of randomization until the date of death from any cause
  • pathological complete response (pCR) rate [ Time Frame: up to 2 year ]
    the rate of no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SHR-1210 Combined With Trastuzumab , Oxaliplatin and Capecitabine for Neoadjuvant Therapy of Gastric Adenocarcinoma/Gastroesophageal Junction Adenocarcinoma
Official Title  ICMJE Phase II Clinical Study of PD1 Antibody (SHR-1210) Combined With Trastuzumab, Oxaliplatin and Capecitabine for Neoadjuvant Therapy of Gastric Adenocarcinoma/Gastroesophageal Junction Adenocarcinoma
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Gastric Cancer
Intervention  ICMJE Drug: SHR-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.
Study Arms  ICMJE Experimental: SHR-1210+ Trastuzumab + Oxaliplatin + Capecitabine
trastuzumab + SHR-1210 + capecitabine + oxaliplatin for neoadjuvant chemotherapy 4-cycle.Then D2 radical surgery. The patients continued to receive capecitabine plus oxaliplatin for adjuvant therapy, and the total number of chemotherapy cycles was 8 cycles.
Intervention: Drug: SHR-1210 Combined With Trastuzumab , Oxaliplatin and Capecitabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 13, 2019)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 1, 2022
Estimated Primary Completion Date December 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ning Li 13526501903 lining97@126.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03950271
Other Study ID Numbers  ICMJE GCCG7
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Henan Cancer Hospital
Study Sponsor  ICMJE Henan Cancer Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Suxia Luo Henan Cancer Hospital
PRS Account Henan Cancer Hospital
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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