Clinical Trials /

Efficacy and Safety of Perioperative Chemotherapy Plus PD-1 Antibody in Gastric Cancer

NCT04367025

Description:

For locally advanced gastric cance, neoadjuvant chemotherapy can increase the resectability of tumor, and finally improve the long-term survival. Combination of perioperative PD-1 antibody and chemotherapy for locally advanced gastric cancer could be a novel therapy to increase response rate and resectability and reduce recurrence rate. Camrelizumab(SHR-1210) in this study is a Chinese anti-PD-1 monoclonal antibody for injection which has been approved for melanoma and Hepatocellular carcinoma. This study is a single center, open-label, randomized comparative phase II clinical trial to evaluate safety and efficacy of Camrelizumab in combination with perioperative chemotherapy in locally advanced adenocarcinoma of stomach or gastroesophageal junction. Differences in T cell expression were detected by single cell RNA sequencing to screen people who were more sensitive to immunotherapy.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Efficacy and Safety of Perioperative Chemotherapy Plus PD-1 Antibody in Gastric Cancer
  • Official Title: Efficacy and Safety of Perioperative Chemotherapy Plus PD-1 Antibody (Camrelizumabin) the Locally Advanced Adenocarcinoma of Stomach or Gastroesophageal Junction

Clinical Trial IDs

  • ORG STUDY ID: OBU-BJ-GC-II-007
  • NCT ID: NCT04367025

Conditions

  • Gastric Cancer

Interventions

DrugSynonymsArms
CamrelizumabSHR-1210Camrelizumab+ SOX
OxaliplatinOXACamrelizumab+ SOX
S1SOX

Purpose

For locally advanced gastric cance, neoadjuvant chemotherapy can increase the resectability of tumor, and finally improve the long-term survival. Combination of perioperative PD-1 antibody and chemotherapy for locally advanced gastric cancer could be a novel therapy to increase response rate and resectability and reduce recurrence rate. CamrelizumabSHR-1210) in this study is a Chinese anti-PD-1 monoclonal antibody for injection which has been approved for melanoma and Hepatocellular carcinoma. This study is a single center, open-label, randomized comparative phase II clinical trial to evaluate safety and efficacy of Camrelizumab in combination with perioperative chemotherapy in locally advanced adenocarcinoma of stomach or gastroesophageal junction. Differences in T cell expression were detected by single cell RNA sequencing to screen people who were more sensitive to immunotherapy.

Detailed Description

      Gastric cancer is one of the most common malignancies in China with incidence and mortality
      both ranking the 2nd among malignancies in China. Surgery is the only possible way to cure
      gastric cancer, however, over 80-90% of gastric cancer patients in China are in advanced
      stage. Locally advanced gastric cancer could be cured by multi-disciplinary therapies
      including surgery, chemotherapy and radiotherapy. Neoadjuvant chemotherapy can increase the
      resectability of tumor, and finally improve the long-term survival. However, the therapeutic
      effects remain unsatisfactory.

      Combination of perioperative PD-1 antibody and chemotherapy for locally advanced gastric
      cancer could be a novel therapy to increase response rate and resectability and reduce
      recurrence rate. Camrelizumab in this study is a Chinese anti-PD-1 monoclonal antibody for
      injection which has been approved for melanoma and Hepatocellular carcinoma .This study is a
      single center, open-label, randomized comparative phase II clinical trial to evaluate safety
      and efficacy of Camrelizumab in combination with perioperative chemotherapy in locally
      advanced adenocarcinoma of stomach or gastroesophageal junction. Differences in T cell
      expression were detected by single cell RNA sequencing to screen people who were more
      sensitive to immunotherapy.
    

Trial Arms

NameTypeDescriptionInterventions
SOXActive ComparatorSOX: Oxaliplatin+S-1 Oxaliplatin: 130mg/m2, iv drip for 2h, d1, q3w; S-1:40~60mg Bid, d1~14, q3w; Neoadjuvant chemotherapy for 2-4 cycles, adjuvant chemotherapy for 2-4 cycles
  • Oxaliplatin
  • S1
Camrelizumab+ SOXExperimentalCamrelizumab:200mg,iv drip for 1h,d1,q3w SOX: Oxaliplatin+S-1 Oxaliplatin: 130mg/m2, iv drip for 2h, d1, q3w; S-1:40~60mg Bid, d1~14, q3w; Neoadjuvant chemotherapy+ Camrelizumab for 2-4 cycles, adjuvant chemotherapy + Camrelizumab for 2-4 cycles.
  • Camrelizumab
  • Oxaliplatin

Eligibility Criteria

        Inclusion Criteria:

          1. Written (signed) informed consent.

          2. Age ≥ 18 years and ≤70 years.

          3. ECOG Performance status 0-1.

          4. Has previously untreated localized gastric or gastroesophageal junction adenocarcinoma
             as defined by T3 or greater primary lesion or the presence of any positive nodes - N+
             (clinical nodes) without evidence of metastatic disease.

          5. Patients who plan surgery after neoadjuvant chemotherapy based on clinical staging
             criteria.

          6. Consent to send tumor tissue from biopsy or resection for PD-L1 detection and PD-L1
             CPS≥1;

          7. Expected survival ≥6 months;

          8. Females of child bearing age must have a negative pregnancy test

          9. 1)Platelet (PLT) ≥100×109/L; 2) Neutrophil count (ANC)≥1.5×l09/L; 3) Hemoglobin (Hb)
             level ≥9.0 g/dl; 4)WBC≥3.5×l09/L; 5) International normalized ratio (INR) ≤1.5; 5)
             Prothrombin time (PT) ,International Normalized Ratio(INR)and activated partial
             thromboplastin time (APTT) ≤1.5×ULN; 6)Total bilirubin (TBIL) level ≤1.5×ULN(patients
             with gilbert syndrome≤3×ULN); 7) Alanine aminotransferase (ALT) and aspartate
             aminotransferase (AST) level ≤2.5×ULN ; 10) Serum creatinine (Cr) level ≤1.5×ULN and
             creatinine clearance ≥60 ml/min;

        Exclusion Criteria:

          1. Patients with pathologically confirmed gastric squamous cell carcinoma, adenosquamous
             carcinoma, small cell carcinoma, and undifferentiated gastric cancer.

          2. patients who have HER2 positive confiemed with IHC3+ or IHC2+ and FISH positive.

          3. Patients with a history of t Anticancer or Experimental Therapy(Including
             chemotherapy, radiotherapy, hormone therapy and molecular targeted therapy)

          4. The patient's cardia or pylorus is nearly obstructed, affecting eating and gastric
             emptying

          5. Immunotherapy with previous anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or
             anti-CTLA-4 antibodies or any other antibody or drug that targets T-cell
             co-stimulation or immune checkpoint pathways

          6. Patients have experienced or currently has other malignancies within 5 years.Except
             for the cured cervical carcinoma in situ,Non-melanoma skin cancer, Other tumors or
             cancers that have been treated radically and have shown no signs of disease for at
             least 5 years.

          7. Peripheral neuropathy ≥ level 2(according to CTCAE 5.0)

          8. Patient currently has CNS or cancerous meningitis.

          9. Patients are allergic to study medication and its ingredients

         10. Patients have hereditary bleeding or coagulopathy at risk of bleeding

         11. Patient underwent major surgery within 4 weeks

         12. Patients have taken Chinese herbal medicine or proprietary Chinese medicine for cancer
             treatment within two weeks

         13. Patients have not recovered from complications of previous surgery.According to the
             CTCAE 5.0, it has not been reduced below level 1(In addition to hair loss and fatigue)

         14. Patients require immunosuppressive drugs within 2 weeks or less or during the
             study.Exclude the following:

             A) Use of intranasal, inhaled or topical steroid(For example, intra - articular
             injection) B) physiological dose of steroid ( Prednisone less than 10mg per day or use
             equivalent dose) C) Short-term(no more than 7 day) use of steroids to prevent or treat
             non-autoimmune allergic diseases

         15. Patients have an active or history of autoimmune disease that may recur

         16. Patients have a history of interstitial lung disease or non-infectious pneumonia

         17. Patients have a history of active tuberculosis

         18. Patients have a history of HIV infection or other acquired, congenital
             immunodeficiency disease , organ transplant or stem cell transplant

         19. Hepatitis B or C virus virological tests meet any of the following:

             A) HBsAg positive ,HBV-DNA≥150 copies/mL or ≥2000IU/mL B) HCV antibody positive and
             HCV-RNA is above the detection limit of the analysis method

         20. Within 2 weeks or 2 weeks before randomization,Patients have an active or
             uncontrollable infection that requires systemic treatment

         21. Patient vaccinated with live virus within 4 weeks

         22. Patients have uncontrollable pleural effusion, pericardial effusion, or ascites
             requiring repeated drainage or treatment.

         23. Patients have gastrointestinal perforation or fistula within 6 months and significant
             clinically significant gastrointestinal bleeding before 3 months of randomization

         24. Patient have intestinal obstruction, inflammatory bowel disease, extensive bowel
             resection, Crohn's disease, ulcerative colitis or chronic diarrhea

         25. Patients have serious internal medicine diseases

         26. Women who are pregnant, breast-feeding or planning to become pregnant during treatment
             or within 6 months after treatment ends.

         27. Patients are unwilling to receive effective contraception during treatment and within
             6 months after treatment ends

         28. The investigator believes that the subject is not suitable for the study
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Major pathologic response (MPR)
Time Frame:At time of surgery
Safety Issue:
Description:It is defined as residual tumors less than 10% after neoadjuvant chemotherapy.

Secondary Outcome Measures

Measure:Objective response rate(ORR)
Time Frame:From the initiation date of first cycle (each cycle is 21 days) to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years
Safety Issue:
Description:It is defined as the proportion of patients whose tumors shrink to a predetermined size and maintain a minimum time limit. It includes the cases of CR and PR.
Measure:pCR
Time Frame:From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks
Safety Issue:
Description:Pathological complete response
Measure:Disease-free survival (DFS)
Time Frame:3years
Safety Issue:
Description:The time from the beginning of randomization to the recurrence of the disease or the death of the patient due to disease progression
Measure:Overall survival(OS)
Time Frame:From the initiation date of first cycle to the date of first documented progression or date of death from any cause, whichever came first,assessed up to 3 years
Safety Issue:
Description:The Kaplan-Meier survival from the initiation date of first cycle until death from any cause or the last follow-up date.
Measure:OSR
Time Frame:3years
Safety Issue:
Description:overall survival rate

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Chinese PLA General Hospital

Trial Keywords

  • Gastric cancer
  • Camrelizumab
  • neoadjuvant
  • chemotherapy

Last Updated

April 26, 2020