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Conversion Therapy of Disitamab Vedotin Combined With Sintilimab and S-1 in HER2 Overexpression Gastric Cancer

Primary Purpose

Gastric Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Disitamab Vedotin
Sintilimab
S-1
Intraperitoneal chemotherapy with paclitaxel
Sponsored by
Tianjin Medical University Cancer Institute and Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Cancer focused on measuring Conversion therapy, Disitamab Vedotin, HER2 overexpression

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 1) Volunteer to take part in the study ; 2) Age 18~70 (including 70), male or female; 3) Gastric cancer or adenocarcinoma of gastroesophageal junction confirmed by histology and/or cytology; 4) Has a single initial unresectable factor. For example, peritoneal metastasis (P1),Intraperitoneal free cancer cells positive (CY1), Paraaortic lymph node metastasis, liver metastasis (≤ 3 lesions, and ≤ 5 cm for a single lesion), ovarian metastasis; 5) Have not received systematic treatment; 6) The HER2 immunohistochemistry (IHC) test result is IHC 3+or 2+, and the previous test results of the subject (confirmed by the investigator) are acceptable; 7) At least one assessable lesion (RECIST 1.1 ); 8) Expected survival time ≥ 6 months; 9) ECOG 0-1; 10) Major organs are functioning normally; Exclusion Criteria: 1) Have a history of malignant tumors other than gastric cancer, except for the following two cases: The patient has received possible curative treatment and there is no evidence of the disease within 5 years; The resected skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ and other carcinoma in situ were successfully received; 2) Suffering from diseases that affect the absorption, distribution, metabolism or clearance of the study drug (such as severe vomiting, chronic diarrhea, intestinal obstruction, absorption disorder, etc.); 3) Have received allogeneic stem cells or solid organ transplantation in the past; 4) Patients who have received other anti-tumor systemic therapy in the past (including traditional Chinese medicine with anti-tumor indications), and have been less than 4 weeks from the completion of treatment to the administration of this study, or the adverse events caused by previous treatment have not recovered to ≤ CTCAE level 1 (except hair loss and pigmentation); 5) Previous or current congenital or acquired immunodeficiency disease; 6) Active or previously recorded autoimmune diseases or inflammatory diseases (including but not limited to: autoimmune hepatitis, interstitial pneumonia, inflammatory bowel disease, systemic lupus erythematosus, vasculitis, uveitis, hypophysitis, hyperthyroidism or hypothyroidism, asthma requiring bronchodilators, etc.), vitiligo or asthma that has completely alleviated in childhood, Those who do not need any intervention after adulthood can be included; 7) Systemic immunosuppressive drugs were used within 2 weeks before enrollment, or were expected to be required during the study, except for the following: d) Corticosteroids for intranasal, inhalation, external or local injection (such as intra-articular injection); e) The dose of prednisone or other equivalent systemic corticosteroids does not exceed 10 mg/day; f) Preventive use of corticosteroids for hypersensitivity; 8) Allergic to the study drug; 9) Thrombosis or thromboembolism events occurred in the past 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc; 10) Patients at risk for severe bleeding; 11) Cardiovascular diseases with significant clinical significance; 12) Other significant clinical and laboratory abnormalities, which the researchers think affect the safety evaluation; 13) Serious infection in active period or poorly controlled clinically; 14) Not recovered from the operation; 15) Pregnant or lactating women, and women or men with fertility who are unwilling or unable to take effective contraceptive measures; 16) Other situations that the investigator thinks are not suitable for inclusion.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Disitamab Vedotin Combined With Sintilimab and S-1

    Arm Description

    30 HER2 overexpression unresectable gastric cancer patients will enrolle and treate with Disitamab Vedotin, Sintilimab and S-1. During the study period, imaging examinations were conducted every 6-12 weeks to evaluate the tumor and whether it reached the operable standard. The scheme and duration of postoperative adjuvant treatment were determined by the investigator according to the patient's conditions (Sintilimab was recommended to be maintained for 1 year, and other drugs were increased or decreased according to the patient's conditions).

    Outcomes

    Primary Outcome Measures

    R0 resection rate
    The proportion of patients who underwent R0 surgery among all patients.

    Secondary Outcome Measures

    objective response rate (ORR)
    The proportion of patients who achieved patial response and complete reponse per RECIST version 1.1.
    overall survival (OS)
    median OS or OS rate
    Recurrence free survival(RFS)
    median RFS or RFS rate
    safety profile
    The grade and proportion of adverse events, treatment related adverse events, immune-related adverse events (irAEs), serious adverse events, and perioperative complications, etc.

    Full Information

    First Posted
    November 17, 2022
    Last Updated
    November 17, 2022
    Sponsor
    Tianjin Medical University Cancer Institute and Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05627414
    Brief Title
    Conversion Therapy of Disitamab Vedotin Combined With Sintilimab and S-1 in HER2 Overexpression Gastric Cancer
    Official Title
    Clinical Study on the Efficacy and Safety of Disitamab Vedotin Combined With Sintilimab and S-1 in the Conversion Treatment of HER2 Overexpression Unresectable Gastric Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 1, 2023 (Anticipated)
    Primary Completion Date
    June 1, 2024 (Anticipated)
    Study Completion Date
    January 1, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Tianjin Medical University Cancer Institute and Hospital

    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
    This is a phase II, one-arm study, which is aiming to evaluate the feasibility of combination of Disitamab Vedotin, Sintilimab and S-1 as conversion therapy in patients with HER2 overexpression unresectable gastric cancer .
    Detailed Description
    In this study, 30 HER2 overexpression unresectable gastric cancer patients will enrolle and treate with Disitamab Vedotin, Sintilimab and S-1. During the study period, imaging examinations were conducted every 6-12 weeks to evaluate the tumor and whether it reached the operable standard. The scheme and duration of postoperative adjuvant treatment were determined by the investigator according to the patient's conditions (Sintilimab was recommended to be maintained for 1 year, and other drugs were increased or decreased according to the patient's conditions). During the study, safety evaluation and effectiveness evaluation will be conducted.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Gastric Cancer
    Keywords
    Conversion therapy, Disitamab Vedotin, HER2 overexpression

    7. Study Design

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

    8. Arms, Groups, and Interventions

    Arm Title
    Disitamab Vedotin Combined With Sintilimab and S-1
    Arm Type
    Experimental
    Arm Description
    30 HER2 overexpression unresectable gastric cancer patients will enrolle and treate with Disitamab Vedotin, Sintilimab and S-1. During the study period, imaging examinations were conducted every 6-12 weeks to evaluate the tumor and whether it reached the operable standard. The scheme and duration of postoperative adjuvant treatment were determined by the investigator according to the patient's conditions (Sintilimab was recommended to be maintained for 1 year, and other drugs were increased or decreased according to the patient's conditions).
    Intervention Type
    Drug
    Intervention Name(s)
    Disitamab Vedotin
    Other Intervention Name(s)
    RC48
    Intervention Description
    2.5mg/kg,IV,Q3W
    Intervention Type
    Drug
    Intervention Name(s)
    Sintilimab
    Other Intervention Name(s)
    TYVYT
    Intervention Description
    200 mg,IV,Q3W
    Intervention Type
    Drug
    Intervention Name(s)
    S-1
    Other Intervention Name(s)
    Tegafur,Gimeracil and Oteracil Potassium Capsules
    Intervention Description
    40~60mg / m2, bid, d1-14, repeated every 3 weeks.
    Intervention Type
    Procedure
    Intervention Name(s)
    Intraperitoneal chemotherapy with paclitaxel
    Other Intervention Name(s)
    Paclitaxel (PTX)
    Intervention Description
    Paclitaxel (PTX) was used with a dose of 60mg / m2, Q3W. (Only for patients with peritoneal metastases)
    Primary Outcome Measure Information:
    Title
    R0 resection rate
    Description
    The proportion of patients who underwent R0 surgery among all patients.
    Time Frame
    1 year
    Secondary Outcome Measure Information:
    Title
    objective response rate (ORR)
    Description
    The proportion of patients who achieved patial response and complete reponse per RECIST version 1.1.
    Time Frame
    up to one year
    Title
    overall survival (OS)
    Description
    median OS or OS rate
    Time Frame
    From the first dose to death from any cause, up to two years.
    Title
    Recurrence free survival(RFS)
    Description
    median RFS or RFS rate
    Time Frame
    From the first dose to recurrence or death from any cause, up to two years.
    Title
    safety profile
    Description
    The grade and proportion of adverse events, treatment related adverse events, immune-related adverse events (irAEs), serious adverse events, and perioperative complications, etc.
    Time Frame
    up to 30 days after last treatment administration

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 1) Volunteer to take part in the study ; 2) Age 18~70 (including 70), male or female; 3) Gastric cancer or adenocarcinoma of gastroesophageal junction confirmed by histology and/or cytology; 4) Has a single initial unresectable factor. For example, peritoneal metastasis (P1),Intraperitoneal free cancer cells positive (CY1), Paraaortic lymph node metastasis, liver metastasis (≤ 3 lesions, and ≤ 5 cm for a single lesion), ovarian metastasis; 5) Have not received systematic treatment; 6) The HER2 immunohistochemistry (IHC) test result is IHC 3+or 2+, and the previous test results of the subject (confirmed by the investigator) are acceptable; 7) At least one assessable lesion (RECIST 1.1 ); 8) Expected survival time ≥ 6 months; 9) ECOG 0-1; 10) Major organs are functioning normally; Exclusion Criteria: 1) Have a history of malignant tumors other than gastric cancer, except for the following two cases: The patient has received possible curative treatment and there is no evidence of the disease within 5 years; The resected skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ and other carcinoma in situ were successfully received; 2) Suffering from diseases that affect the absorption, distribution, metabolism or clearance of the study drug (such as severe vomiting, chronic diarrhea, intestinal obstruction, absorption disorder, etc.); 3) Have received allogeneic stem cells or solid organ transplantation in the past; 4) Patients who have received other anti-tumor systemic therapy in the past (including traditional Chinese medicine with anti-tumor indications), and have been less than 4 weeks from the completion of treatment to the administration of this study, or the adverse events caused by previous treatment have not recovered to ≤ CTCAE level 1 (except hair loss and pigmentation); 5) Previous or current congenital or acquired immunodeficiency disease; 6) Active or previously recorded autoimmune diseases or inflammatory diseases (including but not limited to: autoimmune hepatitis, interstitial pneumonia, inflammatory bowel disease, systemic lupus erythematosus, vasculitis, uveitis, hypophysitis, hyperthyroidism or hypothyroidism, asthma requiring bronchodilators, etc.), vitiligo or asthma that has completely alleviated in childhood, Those who do not need any intervention after adulthood can be included; 7) Systemic immunosuppressive drugs were used within 2 weeks before enrollment, or were expected to be required during the study, except for the following: d) Corticosteroids for intranasal, inhalation, external or local injection (such as intra-articular injection); e) The dose of prednisone or other equivalent systemic corticosteroids does not exceed 10 mg/day; f) Preventive use of corticosteroids for hypersensitivity; 8) Allergic to the study drug; 9) Thrombosis or thromboembolism events occurred in the past 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc; 10) Patients at risk for severe bleeding; 11) Cardiovascular diseases with significant clinical significance; 12) Other significant clinical and laboratory abnormalities, which the researchers think affect the safety evaluation; 13) Serious infection in active period or poorly controlled clinically; 14) Not recovered from the operation; 15) Pregnant or lactating women, and women or men with fertility who are unwilling or unable to take effective contraceptive measures; 16) Other situations that the investigator thinks are not suitable for inclusion.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Han Liang, Master
    Phone
    +8602223340123
    Ext
    1061
    Email
    tjlianghan@126.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Xiaona Wang, Doctor
    Phone
    +8602223340123
    Ext
    1061
    Email
    xiaonawang@hotmail.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Han Liang, Master
    Organizational Affiliation
    ianjin Medical University Cancer Institute and Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Conversion Therapy of Disitamab Vedotin Combined With Sintilimab and S-1 in HER2 Overexpression Gastric Cancer

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