4006-776-356 出国就医服务电话

免费获得国外相关药品,最快 1 个工作日回馈药物信息

出境医 / 临床实验 / PD-1 Inhibitor Combined With FOLFOX Neoadjuvant Therapy for Resectable Gastric and Gastroesophageal Junctional Adenocarcinoma

PD-1 Inhibitor Combined With FOLFOX Neoadjuvant Therapy for Resectable Gastric and Gastroesophageal Junctional Adenocarcinoma

Study Description
Brief Summary:
The aim of this study is to observe the efficacy, safety, postoperative pathological response rate and survival benefit of immume checkpoint inhibitor PD-1 SHR1210 combined with chemotherapy in neoadjuvant therapy of locally advanced resectable gastric and gastroesophageal junction adenocarcinoma. In addition ,the investigators will explore the relationship between the immunophenotype of gastric cancer and the efficacy and drug resistance of immunotherapy combined with chemotherapy, and screen out biomarkers that can predict the efficacy of immunotherapy.

Condition or disease Intervention/treatment Phase
Gastric Cancer Drug: SHR1210 combined with FOLFOX Phase 2

Detailed Description:
Neoadjuvant chemotherapy and neoadjuvant radiotherapy and chemotherapy can not only improve the surgical resection rate and postoperative pathological remission rate, but also prolong the postoperative recurrence-free survival and benefit patients.Recent studies have confirmed that immume point inhibitors PD-1 and CTLA-4 monoclonal antibody have a certain effect in advanced gastric and gastroesophageal junction adenocarcinoma which had experienced multi-line treatment. Furthermore,the FOLFOX protocol is recommended as a new adjuvant treatment for locally advanced gastric cancer.In order to further improve the surgical resection rate and survival rate by improving the efficacy of neoadjuvant therapy for locally advanced gastric and gastroesophageal junction adenocarcinoma, the investigators selected PD-1 monoclonal antibody combined with FOLFOX neoadjuvant therapy for locally advanced gastric and gastroesophageal junctions Adenocarcinoma.The aim of this study is to observe the efficacy, safety, postoperative pathological response rate and survival benefit of immume checkpoint inhibitor PD-1 SHR1210 combined with chemotherapy in neoadjuvant therapy of locally advanced resectable gastric and gastroesophageal junction adenocarcinoma. In addition ,the investigators will explore the relationship between the immunophenotype of gastric cancer and the efficacy and drug resistance of immunotherapy combined with chemotherapy, and screen out biomarkers that can predict the efficacy of immunotherapy.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ⅱ Study of PD-1 Inhibitor Combined With FOLFOX Neoadjuvant Therapy for Resectable Gastric and Gastroesophageal Junctional Adenocarcinoma
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : June 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: treatment group
SHR1210 combined with FOLFOX repeat every 14 days for a total of 4 cycles.
Drug: SHR1210 combined with FOLFOX
  1. SHR1210, iv, 200 mg d1, 30-minute intravenous infusion, repeated every 14 days.
  2. mFOLFOX6:Oxaliplatin 85mg/m2 ivgtt 2h d1,5-fluorouracil 400mg/m2 iv d1,leucovorin 400mg/m2 ivgtt 2h d1,5-fluorouracil 2.4mg/m2 CIV 46h, repeated every 14 days Patients who have no disease progression and can tolerate surgery receive surgery. When the investigator believes that the patient is not suitable for continued medication or according to the RECIST 1.1 standard, the evaluation is PD and the medication is over. The PD-1 monoclonal antibody does not allow for reductions and can only delay or suspend medication.

Outcome Measures
Primary Outcome Measures :
  1. R0 resection rate [ Time Frame: up to 2 years ]
    Tumor tissue was completely resected as a percentage of all surgical patients

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


Secondary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: up to 2 years ]
    From date of randomization until the date of first documented progression or date of death from any cause

  2. Overall survival(OS) [ Time Frame: up to 2 years ]
    the first day of treatment to death or last survival confirm date


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 73 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 18-73 years old; male or female
  2. confirmed gastric and gastroesophageal junction adenocarcinoma by Gastroscopic biopsy histopathological examination
  3. Imaging (CT/MRI) and ultrasound gastroscopy confirmed: cT ≥ T2 and / or regional lymph node positive (N +);
  4. ECOG score: 0~2 points;
  5. Expected survival period ≥ 12 weeks;
  6. A histological specimen can be provided for secondary testing;
  7. The main organ function meets the following criteria within 7 days before treatment:

    Blood routine examination criteria (without blood transfusion within 14 days):

    Hemoglobin (HB) ≥ 90g / L; The absolute value of neutrophils (ANC) ≥ 1.5 × 109 / L; Platelet (PLT) ≥ 80 × 109 / L (2) Biochemical examinations must meet the following criteria: Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); Alanine aminotransferase (ALT) Aspartate aminotransferase (AST) ≤ 2.5 * ULN; serum creatinine (Cr) ≤ 1.5 * ULN or creatinine clearance (CCr) ≥ 60ml / min; (3) Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ normal low limit (50%).

  8. Women of childbearing age should agree to use contraceptives (such as intrauterine devices, contraceptives or condoms) during the study period and within 6 months after the end of the study; negative serum or urine pregnancy test within 7 days prior to study enrollment and must be non-lactating patients; men should agree to patients who must use contraception during the study period and within 6 months after the end of the study period.
  9. The patient volunteered to participate in the study and signed an informed consent form;

Exclusion Criteria:

  1. Exceeding or currently suffering from other malignant tumors within 5 years, except for cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (in situ carcinoma) And T1 (tumor infiltrating basement membrane)];
  2. Patients with a high risk of bleeding or fistula due to the apparent invasion of adjacent organs (aorta or trachea);
  3. Before starting treatment, subject administrated corticosteroids (day> 10 mg equivalent dose prednisone), or other immunosuppressive drugs for systemic treatment of a disease within 14 days . In the absence of active autoimmune disease, >10 mg of daily prednisone equivalent dose of inhaled or topical steroid and adrenal replacement steroid doses are permitted;
  4. Anyone who has received any anti-tumor treatment in the past;
  5. Significantly malnourished patients. Exclusion is performed if the patient is receiving intravenous fluids or is required to be hospitalized for continuous infusion therapy. Patients with good nutrition control ≥ 28 days can be enrolled before randomization;
  6. Participants who received live/attenuated vaccine within 30 days of the first treatment;
  7. Unresolved toxicity due to any previous treatment above CTC AE4.0 Level 2, excluding neurotoxicity of ≤2 caused by hair loss and oxaliplatin;
  8. Allergic reactions and adverse drug reactions:

    1. a history of allergies to the ingredients of the study drug;
    2. contraindications to any study drug (fluorouracil or oxaliplatin) in the chemotherapy regimen.
  9. Patients with any severe and/or uncontrolled disease, including:

    1. patients with hypertension who are not well controlled by antihypertensive drug (systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥100 mmHg);
    2. with grade I or higher myocardial ischemia or myocardial infarction, arrhythmia (including QTc ≥ 480ms) and ≥ grade 2 congestive heart failure (New York Heart Association (NYHA) classification);
    3. Severe or uncontrolled disease or active infection (≥CTCAE grade 2 infection), which the investigator believes may increase the risk associated with study participation, study drug administration, or affect the subject's ability to receive study medication;
    4. Renal failure requires hemodialysis or peritoneal dialysis;
    5. a history of immunodeficiency, including HIV-positive or other acquired, congenital immunodeficiency disease, or a history of organ transplantation;
    6. Patients with diabetes who have poor glycemic control (fasting blood glucose (FBG) > 10 mmol/L); subjects with active, known or suspected autoimmune diseases. Subjects with type 1 diabetes, residual hypothyroidism caused by autoimmune thyroiditis requiring hormone replacement therapy, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis or alopecia) can be enrolled;
    7. patients with seizures and requiring treatment;
    8. The subject has an interstitial lung disease that is symptomatic or may interfere with the discovery or management of suspected drug-related lung toxicity; previous and current subjects with a history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-associated pneumonia, severe impaired lung function, etc. that may interfere with the detection and management of suspected drug-related lung toxicity;
  10. Patients with gastrointestinal diseases such as intestinal obstruction (including incomplete intestinal obstruction) or those who may have caused gastrointestinal bleeding, perforation or obstruction;
  11. Patients who underwent surgical treatment, incisional biopsy or significant traumatic injury within 28 days prior to enrollment;
  12. In the 4 weeks prior to enrollment, patients with any bleeding event ≥ CTCAE 3 have unhealed wounds, ulcers or fractures;
  13. Overactive/venous thrombosis events within 3 months, such as cerebrovascular accidents (including transient ischemic attacks), deep static Pulmonary thrombosis and pulmonary embolism;
  14. Prepare or accept previous allogeneic or allogeneic bone marrow transplantation, including liver transplantation;
  15. According to the investigator's judgment, there is a concomitant disease that seriously harms the patient's safety or affects the patient's completion of the study;
  16. Cannot perform biopsy to provide histological specimens;
  17. those who have a history of psychotropic substance abuse and are unable to quit or have a mental disorder; Prepare or accept previous allogeneic or allogeneic bone marrow transplants, including liver transplants;
  18. Urine routine showed urinary protein ≥ 2+ and confirmed 24-hour urine protein quantitation > 1.0 g;
  19. Patients with brain metastases;
  20. Patients who have participated in other clinical trials of anti-tumor drugs within four weeks.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Ying Liu 13783604602 yaya7207@126.com

Sponsors and Collaborators
Henan Cancer Hospital
Investigators
Layout table for investigator information
Principal Investigator: Ying Liu HeNanHenan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university
Tracking Information
First Submitted Date  ICMJE May 4, 2019
First Posted Date  ICMJE May 7, 2019
Last Update Posted Date May 8, 2019
Estimated Study Start Date  ICMJE June 2019
Estimated Primary Completion Date June 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 4, 2019)
  • R0 resection rate [ Time Frame: up to 2 years ]
    Tumor tissue was completely resected as a percentage of all surgical patients
  • pathological complete response (pCR) rate [ Time Frame: up to 2 years ]
    the rate of no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 4, 2019)
  • Progression-free Survival (PFS) [ Time Frame: up to 2 years ]
    From date of randomization until the date of first documented progression or date of death from any cause
  • Overall survival(OS) [ Time Frame: up to 2 years ]
    the first day of treatment to death or last survival confirm date
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 PD-1 Inhibitor Combined With FOLFOX Neoadjuvant Therapy for Resectable Gastric and Gastroesophageal Junctional Adenocarcinoma
Official Title  ICMJE Phase Ⅱ Study of PD-1 Inhibitor Combined With FOLFOX Neoadjuvant Therapy for Resectable Gastric and Gastroesophageal Junctional Adenocarcinoma
Brief Summary The aim of this study is to observe the efficacy, safety, postoperative pathological response rate and survival benefit of immume checkpoint inhibitor PD-1 SHR1210 combined with chemotherapy in neoadjuvant therapy of locally advanced resectable gastric and gastroesophageal junction adenocarcinoma. In addition ,the investigators will explore the relationship between the immunophenotype of gastric cancer and the efficacy and drug resistance of immunotherapy combined with chemotherapy, and screen out biomarkers that can predict the efficacy of immunotherapy.
Detailed Description Neoadjuvant chemotherapy and neoadjuvant radiotherapy and chemotherapy can not only improve the surgical resection rate and postoperative pathological remission rate, but also prolong the postoperative recurrence-free survival and benefit patients.Recent studies have confirmed that immume point inhibitors PD-1 and CTLA-4 monoclonal antibody have a certain effect in advanced gastric and gastroesophageal junction adenocarcinoma which had experienced multi-line treatment. Furthermore,the FOLFOX protocol is recommended as a new adjuvant treatment for locally advanced gastric cancer.In order to further improve the surgical resection rate and survival rate by improving the efficacy of neoadjuvant therapy for locally advanced gastric and gastroesophageal junction adenocarcinoma, the investigators selected PD-1 monoclonal antibody combined with FOLFOX neoadjuvant therapy for locally advanced gastric and gastroesophageal junctions Adenocarcinoma.The aim of this study is to observe the efficacy, safety, postoperative pathological response rate and survival benefit of immume checkpoint inhibitor PD-1 SHR1210 combined with chemotherapy in neoadjuvant therapy of locally advanced resectable gastric and gastroesophageal junction adenocarcinoma. In addition ,the investigators will explore the relationship between the immunophenotype of gastric cancer and the efficacy and drug resistance of immunotherapy combined with chemotherapy, and screen out biomarkers that can predict the efficacy of immunotherapy.
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: SHR1210 combined with FOLFOX
  1. SHR1210, iv, 200 mg d1, 30-minute intravenous infusion, repeated every 14 days.
  2. mFOLFOX6:Oxaliplatin 85mg/m2 ivgtt 2h d1,5-fluorouracil 400mg/m2 iv d1,leucovorin 400mg/m2 ivgtt 2h d1,5-fluorouracil 2.4mg/m2 CIV 46h, repeated every 14 days Patients who have no disease progression and can tolerate surgery receive surgery. When the investigator believes that the patient is not suitable for continued medication or according to the RECIST 1.1 standard, the evaluation is PD and the medication is over. The PD-1 monoclonal antibody does not allow for reductions and can only delay or suspend medication.
Study Arms  ICMJE Experimental: treatment group
SHR1210 combined with FOLFOX repeat every 14 days for a total of 4 cycles.
Intervention: Drug: SHR1210 combined with FOLFOX
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 Unknown status
Estimated Enrollment  ICMJE
 (submitted: May 4, 2019)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 18-73 years old; male or female
  2. confirmed gastric and gastroesophageal junction adenocarcinoma by Gastroscopic biopsy histopathological examination
  3. Imaging (CT/MRI) and ultrasound gastroscopy confirmed: cT ≥ T2 and / or regional lymph node positive (N +);
  4. ECOG score: 0~2 points;
  5. Expected survival period ≥ 12 weeks;
  6. A histological specimen can be provided for secondary testing;
  7. The main organ function meets the following criteria within 7 days before treatment:

    Blood routine examination criteria (without blood transfusion within 14 days):

    Hemoglobin (HB) ≥ 90g / L; The absolute value of neutrophils (ANC) ≥ 1.5 × 109 / L; Platelet (PLT) ≥ 80 × 109 / L (2) Biochemical examinations must meet the following criteria: Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); Alanine aminotransferase (ALT) Aspartate aminotransferase (AST) ≤ 2.5 * ULN; serum creatinine (Cr) ≤ 1.5 * ULN or creatinine clearance (CCr) ≥ 60ml / min; (3) Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ normal low limit (50%).

  8. Women of childbearing age should agree to use contraceptives (such as intrauterine devices, contraceptives or condoms) during the study period and within 6 months after the end of the study; negative serum or urine pregnancy test within 7 days prior to study enrollment and must be non-lactating patients; men should agree to patients who must use contraception during the study period and within 6 months after the end of the study period.
  9. The patient volunteered to participate in the study and signed an informed consent form;

Exclusion Criteria:

  1. Exceeding or currently suffering from other malignant tumors within 5 years, except for cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non-invasive tumor), Tis (in situ carcinoma) And T1 (tumor infiltrating basement membrane)];
  2. Patients with a high risk of bleeding or fistula due to the apparent invasion of adjacent organs (aorta or trachea);
  3. Before starting treatment, subject administrated corticosteroids (day> 10 mg equivalent dose prednisone), or other immunosuppressive drugs for systemic treatment of a disease within 14 days . In the absence of active autoimmune disease, >10 mg of daily prednisone equivalent dose of inhaled or topical steroid and adrenal replacement steroid doses are permitted;
  4. Anyone who has received any anti-tumor treatment in the past;
  5. Significantly malnourished patients. Exclusion is performed if the patient is receiving intravenous fluids or is required to be hospitalized for continuous infusion therapy. Patients with good nutrition control ≥ 28 days can be enrolled before randomization;
  6. Participants who received live/attenuated vaccine within 30 days of the first treatment;
  7. Unresolved toxicity due to any previous treatment above CTC AE4.0 Level 2, excluding neurotoxicity of ≤2 caused by hair loss and oxaliplatin;
  8. Allergic reactions and adverse drug reactions:

    1. a history of allergies to the ingredients of the study drug;
    2. contraindications to any study drug (fluorouracil or oxaliplatin) in the chemotherapy regimen.
  9. Patients with any severe and/or uncontrolled disease, including:

    1. patients with hypertension who are not well controlled by antihypertensive drug (systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥100 mmHg);
    2. with grade I or higher myocardial ischemia or myocardial infarction, arrhythmia (including QTc ≥ 480ms) and ≥ grade 2 congestive heart failure (New York Heart Association (NYHA) classification);
    3. Severe or uncontrolled disease or active infection (≥CTCAE grade 2 infection), which the investigator believes may increase the risk associated with study participation, study drug administration, or affect the subject's ability to receive study medication;
    4. Renal failure requires hemodialysis or peritoneal dialysis;
    5. a history of immunodeficiency, including HIV-positive or other acquired, congenital immunodeficiency disease, or a history of organ transplantation;
    6. Patients with diabetes who have poor glycemic control (fasting blood glucose (FBG) > 10 mmol/L); subjects with active, known or suspected autoimmune diseases. Subjects with type 1 diabetes, residual hypothyroidism caused by autoimmune thyroiditis requiring hormone replacement therapy, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis or alopecia) can be enrolled;
    7. patients with seizures and requiring treatment;
    8. The subject has an interstitial lung disease that is symptomatic or may interfere with the discovery or management of suspected drug-related lung toxicity; previous and current subjects with a history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-associated pneumonia, severe impaired lung function, etc. that may interfere with the detection and management of suspected drug-related lung toxicity;
  10. Patients with gastrointestinal diseases such as intestinal obstruction (including incomplete intestinal obstruction) or those who may have caused gastrointestinal bleeding, perforation or obstruction;
  11. Patients who underwent surgical treatment, incisional biopsy or significant traumatic injury within 28 days prior to enrollment;
  12. In the 4 weeks prior to enrollment, patients with any bleeding event ≥ CTCAE 3 have unhealed wounds, ulcers or fractures;
  13. Overactive/venous thrombosis events within 3 months, such as cerebrovascular accidents (including transient ischemic attacks), deep static Pulmonary thrombosis and pulmonary embolism;
  14. Prepare or accept previous allogeneic or allogeneic bone marrow transplantation, including liver transplantation;
  15. According to the investigator's judgment, there is a concomitant disease that seriously harms the patient's safety or affects the patient's completion of the study;
  16. Cannot perform biopsy to provide histological specimens;
  17. those who have a history of psychotropic substance abuse and are unable to quit or have a mental disorder; Prepare or accept previous allogeneic or allogeneic bone marrow transplants, including liver transplants;
  18. Urine routine showed urinary protein ≥ 2+ and confirmed 24-hour urine protein quantitation > 1.0 g;
  19. Patients with brain metastases;
  20. Patients who have participated in other clinical trials of anti-tumor drugs within four weeks.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 73 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03939962
Other Study ID Numbers  ICMJE HNGC-004
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: Ying Liu HeNanHenan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university
PRS Account Henan Cancer Hospital
Verification Date May 2019

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

治疗医院