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To Evaluate the Efficacy and Safety of Cadonilimab With SOX as Neoadjuvant Therapy for Resectable Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma.

Primary Purpose

Gastric Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
S-1, Oxaliplatin, Cadonilimab
Sponsored by
Sichuan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Cancer focused on measuring gastric cancer, neoadjuvant therapy, Cadonilimab

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age 18-75 years. Histologically or cytologically confirmed diagnosis of adenocarcinoma locate at gastroesophageal junction or stomach, advanced gastric or gastroesophageal junction cancer as assessed by ultrasonography and/or CT/MRI (cT3-T4a, N+, M0). Resectable gastric or gastroesophageal cancer, judged by surgeons in this study. No previous anti-tumor treatment. The expected survival is no less than 3 months. ECOG PS≤1. Adequate organ function including the following: Total bilirubin ≤1.5 times upper limit of normal (ULN), Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3×ULN, Alkaline phosphatase≤2.5×ULN (If the tumor invaded the liver, ≤3×ULN), Serum creatinine≤1.5×ULN, Serum amylase and lipase≤1.5×ULN, International standardized ratio (INR)/partial prothrombin time (PTT)≤1.5×ULN; Platelet count ≥ 75,000 /mm3. Hemoglobin (Hb) ≥ 9 g/dL. Absolute neutrophil count (ANC) ≥ 1500/mm3. Strict contraception. Patients must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure. Exclusion Criteria: Unable to comply with the research program or procedures. Undergoing other drug clinical trials, or has participated in any drug clinical trials one month before enrollment. Active autoimmune disease or history of refractory autoimmune disease. Receiving corticosteroid (> 10mg/d prednisone or equivalent dose of steroids) or other systematic immunosuppression therapies within 14 days before enrollment, excluding following therapies: steroid hormone replacement therapy (≤10mg/d); local steroid therapy; short-term, prophylactic steroid therapy for preventing allergies or nausea and vomiting. Active or clinically significant cardiac disease: Congestive heart failure > New York Heart Association (NYHA ) class 2; Active coronary artery disease; Arrhythmias requiring treatment other than β-blocker or digoxin; Unstable angina (with angina symptoms at rest), new angina within 3 months before enrollment, or new myocardial infarction within 6 months before enrollment Evidence or history of bleeding diathesis or coagulopathy. Grade 3 bleeding events 4 weeks before enrollment. Thromboembolism or arteriovenous events, such as cerebrovascular events (including transient ischemic attack), deep vein thrombosis or pulmonary embolism, occurred 6 months before enrollment. Currently taking anticoagulants. Other tumors that have not been treated or exist at the same time, except carcinoma in situ of the cervix, treated basal cell carcinoma or superficial bladder tumor. If the tumor has been cured and no evidence of disease has been found for more than 3 years, the patient can be enrolled. All other tumors must be treated at least 3 years before enrollment. Patients with pheochromocytoma. Patients with a history of HIV infection or active hepatitis B/C. Ongoing > level 2 infection. Symptomatic brain metastasis or meningioma. Unhealed wounds, ulcers or fractures. Renal failure patients requiring blood or peritoneal dialysis. Dehydration≥ 1 grade. Epileptic that need medication. Active, symptomatic interstitial pneumonia, pleural or ascites that causes dyspnea (dyspnea ≥ 2 grade). History of organ transplantation. (including corneal transplantation). Allergic to research drugs or similar drugs, or suspected allergies. Malabsorption patients. Pregnant or lactating women. Investigator believes that patients who are not suitable for the study. Medical, psychological or social conditions can affect the recruitment of patients and evaluation for study results. Other anti-tumor therapy (chemotherapy, radiotherapy, surgery, immunotherapy, biotherapy, chemoembolization) other than investigator drugs. Palliative external irradiation for non-target lesions is allowed. Previously used oxaliplatin, S-1 or Cadonilimab. Major surgery 4 weeks before recruitment, open biopsy or major trauma surgery. (excluding biliary stents, or percutaneous biliary drainage). Treatment with anti-tumor Chinese herbal medicine. History of allogeneic blood transfusion within 6 months.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    SOX+Cadonilimab(AK104)

    Arm Description

    3 cycles of neoadjuvant therapy: S-1: 40~60mg Bid,d1~14, q3w Oxaliplatin:130mg/m2,iv drip,d1, q3w Cadonilimab(AK104):10mg/Kg,iv drip,d1,q3w

    Outcomes

    Primary Outcome Measures

    Pathological complete response rate (pCR)
    evaluate pathological complete response rate of primary tumor and locally metastatic lymph nodes after 3 cycles of neoadjuvant therapy.

    Secondary Outcome Measures

    R0 resection rate
    Rate of microscopically margin-negative resection
    2-year overall survival rate
    2-year disease free survival rate
    major pathological response (MPR)
    Safety and Tolerability
    Treatment-related adverse events as assessed by CTCAE v4.0

    Full Information

    First Posted
    July 10, 2023
    Last Updated
    July 10, 2023
    Sponsor
    Sichuan University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05948449
    Brief Title
    To Evaluate the Efficacy and Safety of Cadonilimab With SOX as Neoadjuvant Therapy for Resectable Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma.
    Official Title
    The Efficacy and Safety of Chemotherapy Combined With Cadonilimab (AK104) in Neoadjuvant Treatment of Locally Advanced Gastric Cancer/Gastroesophageal Junction Adenocarcinoma: A Prospective, Single-arm, Phase II Clinical Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    July 2023 (Anticipated)
    Primary Completion Date
    January 2025 (Anticipated)
    Study Completion Date
    July 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Sichuan University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    The Purpose of This Study is to Evaluate the Efficacy and Safety of Cadonilimab(AK104) in Combination With SOX as Neoadjuvant Therapy for Patients With Resectable Locally Advanced Gastric or Gastroesophageal Adenocarcinoma.
    Detailed Description
    Recent years, neoadjuvant therapy have emerged as a promising treatment option for the treatment of locally advanced gastric or gastroesophageal adenocarcinoma. However, the efficacy of current neoadjuvant regimens is still unsatisfactory. Novel treatment with higher efficacy and safety are urgently needed. Recently, immunotherapy has achieved significant therapeutic effects in the treatment of a series of cancers, and chemotherapy combined with immunotherapy has been recommended as the standard first-line treatment for gastric cancer. Moreover, several phase I/II studies have explored the efficacy and safety of chemotherapy combined with PD-1 inhibitor in the neoadjuvant treatment for gastric cancer, the results of which indicate that chemotherapy combined with immunotherapy can significantly improve the pCR rate and R0 resection rate of gastric cancer. In this study, we will evaluate the efficacy and safety of chemotherapy combined with Cadonilimab(AK104) (a PD-1/CTLA-4 bispecific antibody) in the neoadjuvant therapy for resectable locally advanced gastric or gastroesophageal adenocarcinoma.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Gastric Cancer
    Keywords
    gastric cancer, neoadjuvant therapy, Cadonilimab

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    37 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    SOX+Cadonilimab(AK104)
    Arm Type
    Experimental
    Arm Description
    3 cycles of neoadjuvant therapy: S-1: 40~60mg Bid,d1~14, q3w Oxaliplatin:130mg/m2,iv drip,d1, q3w Cadonilimab(AK104):10mg/Kg,iv drip,d1,q3w
    Intervention Type
    Drug
    Intervention Name(s)
    S-1, Oxaliplatin, Cadonilimab
    Intervention Description
    3 cycles of neoadjuvant therapy will be administered: S-1: 40~60mg Bid,d1~14, q3w Oxaliplatin:130mg/m2,iv drip,d1, q3w Cadonilimab(AK104):10mg/Kg,iv drip,d1,q3w
    Primary Outcome Measure Information:
    Title
    Pathological complete response rate (pCR)
    Description
    evaluate pathological complete response rate of primary tumor and locally metastatic lymph nodes after 3 cycles of neoadjuvant therapy.
    Time Frame
    From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.
    Secondary Outcome Measure Information:
    Title
    R0 resection rate
    Description
    Rate of microscopically margin-negative resection
    Time Frame
    From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.
    Title
    2-year overall survival rate
    Time Frame
    2 years
    Title
    2-year disease free survival rate
    Time Frame
    2 year
    Title
    major pathological response (MPR)
    Time Frame
    From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.
    Title
    Safety and Tolerability
    Description
    Treatment-related adverse events as assessed by CTCAE v4.0
    Time Frame
    3 months after the last administration of drugs

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age 18-75 years. Histologically or cytologically confirmed diagnosis of adenocarcinoma locate at gastroesophageal junction or stomach, advanced gastric or gastroesophageal junction cancer as assessed by ultrasonography and/or CT/MRI (cT3-T4a, N+, M0). Resectable gastric or gastroesophageal cancer, judged by surgeons in this study. No previous anti-tumor treatment. The expected survival is no less than 3 months. ECOG PS≤1. Adequate organ function including the following: Total bilirubin ≤1.5 times upper limit of normal (ULN), Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3×ULN, Alkaline phosphatase≤2.5×ULN (If the tumor invaded the liver, ≤3×ULN), Serum creatinine≤1.5×ULN, Serum amylase and lipase≤1.5×ULN, International standardized ratio (INR)/partial prothrombin time (PTT)≤1.5×ULN; Platelet count ≥ 75,000 /mm3. Hemoglobin (Hb) ≥ 9 g/dL. Absolute neutrophil count (ANC) ≥ 1500/mm3. Strict contraception. Patients must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure. Exclusion Criteria: Unable to comply with the research program or procedures. Undergoing other drug clinical trials, or has participated in any drug clinical trials one month before enrollment. Active autoimmune disease or history of refractory autoimmune disease. Receiving corticosteroid (> 10mg/d prednisone or equivalent dose of steroids) or other systematic immunosuppression therapies within 14 days before enrollment, excluding following therapies: steroid hormone replacement therapy (≤10mg/d); local steroid therapy; short-term, prophylactic steroid therapy for preventing allergies or nausea and vomiting. Active or clinically significant cardiac disease: Congestive heart failure > New York Heart Association (NYHA ) class 2; Active coronary artery disease; Arrhythmias requiring treatment other than β-blocker or digoxin; Unstable angina (with angina symptoms at rest), new angina within 3 months before enrollment, or new myocardial infarction within 6 months before enrollment Evidence or history of bleeding diathesis or coagulopathy. Grade 3 bleeding events 4 weeks before enrollment. Thromboembolism or arteriovenous events, such as cerebrovascular events (including transient ischemic attack), deep vein thrombosis or pulmonary embolism, occurred 6 months before enrollment. Currently taking anticoagulants. Other tumors that have not been treated or exist at the same time, except carcinoma in situ of the cervix, treated basal cell carcinoma or superficial bladder tumor. If the tumor has been cured and no evidence of disease has been found for more than 3 years, the patient can be enrolled. All other tumors must be treated at least 3 years before enrollment. Patients with pheochromocytoma. Patients with a history of HIV infection or active hepatitis B/C. Ongoing > level 2 infection. Symptomatic brain metastasis or meningioma. Unhealed wounds, ulcers or fractures. Renal failure patients requiring blood or peritoneal dialysis. Dehydration≥ 1 grade. Epileptic that need medication. Active, symptomatic interstitial pneumonia, pleural or ascites that causes dyspnea (dyspnea ≥ 2 grade). History of organ transplantation. (including corneal transplantation). Allergic to research drugs or similar drugs, or suspected allergies. Malabsorption patients. Pregnant or lactating women. Investigator believes that patients who are not suitable for the study. Medical, psychological or social conditions can affect the recruitment of patients and evaluation for study results. Other anti-tumor therapy (chemotherapy, radiotherapy, surgery, immunotherapy, biotherapy, chemoembolization) other than investigator drugs. Palliative external irradiation for non-target lesions is allowed. Previously used oxaliplatin, S-1 or Cadonilimab. Major surgery 4 weeks before recruitment, open biopsy or major trauma surgery. (excluding biliary stents, or percutaneous biliary drainage). Treatment with anti-tumor Chinese herbal medicine. History of allogeneic blood transfusion within 6 months.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Jiankun Hu, M.D
    Phone
    +86-18980601504
    Email
    hujiankun@wchscu.cn
    First Name & Middle Initial & Last Name or Official Title & Degree
    Pengfei Zhang
    Phone
    +86-17828163584
    Email
    fly_121988@126.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Jiankun Hu
    Organizational Affiliation
    West China Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    To Evaluate the Efficacy and Safety of Cadonilimab With SOX as Neoadjuvant Therapy for Resectable Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma.

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