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HIPEC Combined With Sintilimab for Gastric Cancer With Peritoneal Metastasis

Primary Purpose

Gastric Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
HIPEC,anti-PD-1 antibody Sintilimab (Tyvyt®), Chemotherapy,Surgery
Sponsored by
Affiliated Cancer Hospital & Institute of Guangzhou Medical 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, Peritoneal Metastasis, HIPEC, PD1

Eligibility Criteria

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

Inclusion Criteria: Advanced gastric (gastroesophageal junction) adenocarcinoma confirmed by histology; Age 18-75 years, Male or Non pregnant female ECOG (Eastern Cooperative Oncology Group) : 0~1; Negative for HER-2 by IHC/FISH; Peritoneal metastasis is confirmed by laparoscopic exploration, and the PCI≤20; Untreated (e.g. radiotherapy, chemotherapy, target therapy and immunotherapy); Normal Bone marrow, liver and kidney function indices before the recruitment: Expected survival≥ 12 week Signed the Informed Consent Form, and blood and tissue samples can be obtained; Exclusion Criteria: Other distal metastases besides peritoneal metastases (e.g., liver, lung, pleural, brain, bone metastases, etc.); Previous systemic therapy for gastric cancer; Recurrent gastric cancer after surgery; Cardiopulmonary dysfunction; Immunosuppressive drugs(eg.Corticosteroids) were used within 14 days before treatment, eg.corticosteroids, There is any active autoimmune disease or a history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or asthma in childhood have been completely relieved, and those who do not need any intervention after adulthood can be included Asthma requiring medical intervention with bronchodilator was not included.) Allergy to the drugs in this protocol; Patients with other diseases not suitable for inclusion, such as immune deficiency, active tuberculosis, hepatitis B (non-active hepatitis B surface antigen (HBsAg) carriers, hepatitis B virus titer <500IU/ml after treatment and with normal liver function can be included), hepatitis C virus positive; A history of idiopathic pulmonary fibrosis, tissue pneumonia, drug pneumonia, idiopathic pneumonia, or r active pneumonia; Other patients who were considered unsuitable for inclusion by the researchers;

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Gastric Cancer With Peritoneal Metastasis, HIPEC, Anti-PD-1 Antibody

    Arm Description

    Surgical exploration, if PCI≤20, then we perform this study. HIPEC: HIPEC is performed after laparoscopic exploration, Mitomycin 30mg/m2, d1, Docetaxel 40mg/m2, d3, Oxaliplatin 65mg/m2, d5 within a week after surgical exploration; Chemotherapy(SOX) and anti-PD-1 antibody Sintilimab (Tyvyt®) treatment followed (4 cycles): SOX regimen: Oxaliplatin: 130 mg/m^2, IV, d1; S-1, 40-60 mg/m^2 bid, po, day 1-14, every 3 weeks for a total of 4 cycles; Sintilimab (Tyvyt®) 200mg fixed dose every 3 weeks, for a total of 4 cycles. Surgery: Imaging and secondary surgical exploration, assess the patient's condition and consider whether perform the cytoreductive surgery (resection of primary tumors and metastases ). After the surgery, HIPEC for three cycles, Mitomycin 30mg/m2, d1, Docetaxel 40mg/m2, d3, Oxaliplatin 65mg/m2, d5 within a week after surgery; For inoperable patients, continue to use standard chemotherapy. After the surgery, continue to use standard adjuvant chemotherapy.

    Outcomes

    Primary Outcome Measures

    R0 resection
    the rate of R0 resection

    Secondary Outcome Measures

    Overall survival time
    Overall survival time(OS) refers to the time of first use of the drug to the time of death. At the end of the study, if the subject is still alive, refer the known "date of last survival of the subject" as the date of censoring.
    ORR
    Objective response rate(ORR): ORR = (number of subjects with complete response (CR) + partial response (PR))/total number of subjects ×100%. Measurable lesion according to the RECISTv1.1
    Event-Free Survival
    Defined as the interval between the first conversion therapy and the first recorded related events, including preoperative disease progression, postoperative disease recurrence, and death from any cause.
    Relapse-Free Survival
    Defined as postoperative the first recorded postoperative recurrence of disease or death from any cause

    Full Information

    First Posted
    December 5, 2022
    Last Updated
    December 14, 2022
    Sponsor
    Affiliated Cancer Hospital & Institute of Guangzhou Medical University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05648487
    Brief Title
    HIPEC Combined With Sintilimab for Gastric Cancer With Peritoneal Metastasis
    Official Title
    A Phase II Study of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Combined With Sintilimab in Gastric Cancer With Peritoneal Metastasis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    December 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 1, 2023 (Anticipated)
    Primary Completion Date
    March 31, 2025 (Anticipated)
    Study Completion Date
    December 31, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Affiliated Cancer Hospital & Institute of Guangzhou Medical University

    4. Oversight

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

    5. Study Description

    Brief Summary
    To evaluate the Safety and Efficacy of HIPEC Combined With Sintilimab for Gastric Cancer Patients with Peritoneal Metastasis.
    Detailed Description
    Peritoneal metastasis is the most common pattern of disease relapse and is attributed to the dismal prognosis of the gastric cancer. The National Comprehensive Cancer Network (NCCN) guidelines suggest that systemic chemotherapy is the first-line standard strategy, and chemotherapy combined with trastuzumab for patients with positive HER-2. HIPEC can significantly improve survival in peritoneal metastasis from gastric cancer. PD-1/PD-L1 antibody has shown promising outcomes for unresectable or metastatic solid tumors. The present study aimed to evaluate the safety and efficacy of HIPEC combined with Sintilimab (Tyvyt®) in gastric cancer patients with peritoneal metastasis.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Gastric Cancer
    Keywords
    Gastric Cancer, Peritoneal Metastasis, HIPEC, PD1

    7. Study Design

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

    8. Arms, Groups, and Interventions

    Arm Title
    Gastric Cancer With Peritoneal Metastasis, HIPEC, Anti-PD-1 Antibody
    Arm Type
    Experimental
    Arm Description
    Surgical exploration, if PCI≤20, then we perform this study. HIPEC: HIPEC is performed after laparoscopic exploration, Mitomycin 30mg/m2, d1, Docetaxel 40mg/m2, d3, Oxaliplatin 65mg/m2, d5 within a week after surgical exploration; Chemotherapy(SOX) and anti-PD-1 antibody Sintilimab (Tyvyt®) treatment followed (4 cycles): SOX regimen: Oxaliplatin: 130 mg/m^2, IV, d1; S-1, 40-60 mg/m^2 bid, po, day 1-14, every 3 weeks for a total of 4 cycles; Sintilimab (Tyvyt®) 200mg fixed dose every 3 weeks, for a total of 4 cycles. Surgery: Imaging and secondary surgical exploration, assess the patient's condition and consider whether perform the cytoreductive surgery (resection of primary tumors and metastases ). After the surgery, HIPEC for three cycles, Mitomycin 30mg/m2, d1, Docetaxel 40mg/m2, d3, Oxaliplatin 65mg/m2, d5 within a week after surgery; For inoperable patients, continue to use standard chemotherapy. After the surgery, continue to use standard adjuvant chemotherapy.
    Intervention Type
    Drug
    Intervention Name(s)
    HIPEC,anti-PD-1 antibody Sintilimab (Tyvyt®), Chemotherapy,Surgery
    Intervention Description
    HIPEC: HIPEC is performed after laparoscopic exploration, Mitomycin 30mg/m2, d1, Docetaxel 40mg/m2, d3, Oxaliplatin 65mg/m2, d5 within a week after surgical exploration. Chemotherapy(SOX) and anti-PD-1 antibody Sintilimab (Tyvyt®) treatment followed (4 cycles): SOX regimen: Oxaliplatin: 130 mg/m^2, IV, d1; S-1, 40-60 mg/m^2 bid, po, day 1-14, every 3 weeks for a total of 4 cycles; Sintilimab (Tyvyt®) 200mg fixed dose every 3 weeks, for a total of 4 cycles. Surgery: Imaging and secondary surgical exploration, assess the patient's condition and consider whether perform the cytoreductive surgery (resection of primary tumors and metastases). For patients undergoing surgery, HIPEC for three cycles followed, Mitomycin 30mg/m2, d1, Docetaxel 40mg/m2, d3, Oxaliplatin 65mg/m2, d5 within a week after surgery; For inoperable patients, continue to use standard chemotherapy of guidelines recommend. After the surgery, continue to use standard adjuvant chemotherapy.
    Primary Outcome Measure Information:
    Title
    R0 resection
    Description
    the rate of R0 resection
    Time Frame
    3 months
    Secondary Outcome Measure Information:
    Title
    Overall survival time
    Description
    Overall survival time(OS) refers to the time of first use of the drug to the time of death. At the end of the study, if the subject is still alive, refer the known "date of last survival of the subject" as the date of censoring.
    Time Frame
    2 years
    Title
    ORR
    Description
    Objective response rate(ORR): ORR = (number of subjects with complete response (CR) + partial response (PR))/total number of subjects ×100%. Measurable lesion according to the RECISTv1.1
    Time Frame
    3 months
    Title
    Event-Free Survival
    Description
    Defined as the interval between the first conversion therapy and the first recorded related events, including preoperative disease progression, postoperative disease recurrence, and death from any cause.
    Time Frame
    2 years
    Title
    Relapse-Free Survival
    Description
    Defined as postoperative the first recorded postoperative recurrence of disease or death from any cause
    Time Frame
    2 years

    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: Advanced gastric (gastroesophageal junction) adenocarcinoma confirmed by histology; Age 18-75 years, Male or Non pregnant female ECOG (Eastern Cooperative Oncology Group) : 0~1; Negative for HER-2 by IHC/FISH; Peritoneal metastasis is confirmed by laparoscopic exploration, and the PCI≤20; Untreated (e.g. radiotherapy, chemotherapy, target therapy and immunotherapy); Normal Bone marrow, liver and kidney function indices before the recruitment: Expected survival≥ 12 week Signed the Informed Consent Form, and blood and tissue samples can be obtained; Exclusion Criteria: Other distal metastases besides peritoneal metastases (e.g., liver, lung, pleural, brain, bone metastases, etc.); Previous systemic therapy for gastric cancer; Recurrent gastric cancer after surgery; Cardiopulmonary dysfunction; Immunosuppressive drugs(eg.Corticosteroids) were used within 14 days before treatment, eg.corticosteroids, There is any active autoimmune disease or a history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or asthma in childhood have been completely relieved, and those who do not need any intervention after adulthood can be included Asthma requiring medical intervention with bronchodilator was not included.) Allergy to the drugs in this protocol; Patients with other diseases not suitable for inclusion, such as immune deficiency, active tuberculosis, hepatitis B (non-active hepatitis B surface antigen (HBsAg) carriers, hepatitis B virus titer <500IU/ml after treatment and with normal liver function can be included), hepatitis C virus positive; A history of idiopathic pulmonary fibrosis, tissue pneumonia, drug pneumonia, idiopathic pneumonia, or r active pneumonia; Other patients who were considered unsuitable for inclusion by the researchers;
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Ziying Lei, Doctor
    Phone
    (086)020-66673666
    Ext
    3772
    Email
    leiziyinggz@126.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Shuzhong Cui, Doctor
    Phone
    086-138-0251-3800
    Email
    cuishuzhong@gzhmu.edu.cn
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Shuzhong Cui, Doctor
    Organizational Affiliation
    Affiliated Cancer Hospital & Institute of Guangzhou Medical University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    28448662
    Citation
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    Results Reference
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    PubMed Identifier
    19777180
    Citation
    Okabe H, Ueda S, Obama K, Hosogi H, Sakai Y. Induction chemotherapy with S-1 plus cisplatin followed by surgery for treatment of gastric cancer with peritoneal dissemination. Ann Surg Oncol. 2009 Dec;16(12):3227-36. doi: 10.1245/s10434-009-0706-z. Epub 2009 Sep 24.
    Results Reference
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    PubMed Identifier
    29746229
    Citation
    Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J. Phase III Trial Comparing Intraperitoneal and Intravenous Paclitaxel Plus S-1 Versus Cisplatin Plus S-1 in Patients With Gastric Cancer With Peritoneal Metastasis: PHOENIX-GC Trial. J Clin Oncol. 2018 Jul 1;36(19):1922-1929. doi: 10.1200/JCO.2018.77.8613. Epub 2018 May 10.
    Results Reference
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    PubMed Identifier
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    Citation
    Yang XJ, Huang CQ, Suo T, Mei LJ, Yang GL, Cheng FL, Zhou YF, Xiong B, Yonemura Y, Li Y. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Ann Surg Oncol. 2011 Jun;18(6):1575-81. doi: 10.1245/s10434-011-1631-5. Epub 2011 Mar 23.
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    PubMed Identifier
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    Citation
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    Results Reference
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    HIPEC Combined With Sintilimab for Gastric Cancer With Peritoneal Metastasis

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