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Neoadjuvant Toripalimab for dMMR/MSI-H Gastric Cancer

Primary Purpose

Gastric or Gastroesophageal Junction Adenocarcinoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
PD-1 inhibitor
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric or Gastroesophageal Junction Adenocarcinoma focused on measuring dMMR/MSI-H, Gastric cancer

Eligibility Criteria

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

Inclusion Criteria: 1. Aged 18-75 years, regardless of gender 2. Patients with histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction and confirmed dMMR or MSI-H 3. Preoperative CT or MRI staging meeting the following criteria: T2 and above, with or without lymph node involvement, without clear distant metastasis 4. ECOG score of 0-1. 5. Expected survival ≥ 2 years. 6. Good organ function (no blood transfusion, no hematopoietic stimulating factor, no albumin or blood product transfusion within 14 days prior to the examination). Platelet (PLT) count ≥ 90*109/L. Neutrophil count (ANC) ≥ 1.5*109/L. Hemoglobin (Hb) level ≥ 9.0 g/dl. International normalized ratio (INR) ≤ 1.5. Prothrombin time (PT) and active partial thromboplastin time (APTT) ≤ 1.5 x ULN. Glycated hemoglobin (HbA1c) <7.5%. Total bilirubin (TBIL) level ≤ 1.5 times the upper limit of normal (ULN). Alanine amino transaminase (ALT) and aspartate amino transaminase (AST) levels ≤ 2.5 x ULN. Serum creatinine (Cr) level ≤ 1.5 x ULN and creatinine clearance ≥ 60 ml/min. Thyrotropin (TSH) ≤ ULN; serum free thyroid hormone (T4) normal; serum free triiodothyronine (T3) normal; (except for those who have received previous thyroid surgery or have a history of head and neck radiotherapy) Serum amylase ≤ 1.5 x ULN. Lipase ≤ 1.5×ULN. 7. Women of childbearing age must have a negative pregnancy test and must use contraception and avoid breastfeeding during the study and for 3 months after the last dose; male subjects must agree to use contraception during the study and for 3 months after the last dose. 8.Be able to understand and willing to sign a written informed consent form. Exclusion Criteria: Previously received chemotherapy, radiotherapy or immunotherapy for gastric cancer Previously diagnosed any other malignancy with a primary site or histological type different from gastric cancer within 5 years prior to study entry, except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix With known hypersensitivity to the study drug or excipients, or to similar drugs Received major surgery or open biopsy, or had a major trauma within 4 weeks prior to the start of study treatment Received immunosuppressive drugs (excluding inhaled corticosteroids or ≤10 mg/day prednisone or equivalent pharmacophysiologic doses of other systemic steroids) within 2 weeks prior to the start of study treatment Planned live attenuated vaccination within 4 weeks prior to the start of study treatment or during the study period Inability to discontinue CYP3A4 inducers or inhibitors within 1 week prior to the start of study treatment and during the study period Presence of any autoimmune disease or history of autoimmune disease. Human immunodeficiency virus (HIV) infection (HIV antibody positive), or active hepatitis C virus (HCV) infection (HCV antibody positive), or active hepatitis B virus (HBV) infection (HBsAg positive and HBV-DNA ≥ 2000 IU/ml copies/ml)), or other serious infection requiring antibiotics for systemic therapy, or during screening/study Unexplained temperature >38.5°C prior to the start of treatment. Presence of the following diseases within 6 months prior to the start of study treatment: myocardial infarction, severe/unstable angina, NYHA class 2 or higher congestive heart failure, poorly controlled arrhythmias, etc. Non-well-controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg under optimal treatment) Arterial/venous thrombotic events such as cerebrovascular accidents (transient ischemic attack, cerebral hemorrhage, cerebral infarction, etc.), deep vein thrombosis, vasculitis, etc. within 3 months prior to the start of study treatment Urine routine suggesting urine protein up to +++ and confirmed 24-hour urine protein quantification up to 1.0g. The presence of a history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation Seizures requiring medication (e.g., steroids or antiepileptic drugs) for treatment. Presence of a history of substance abuse, drug use, or alcohol dependence. Patients with other serious, acute or chronic medical conditions that may increase the risk of study participation and study medication, or that may interfere with the interpretation of study results, and who are judged by the investigator to be unsuitable for participation in a clinical trial.

Sites / Locations

  • Sun Yat-sen University Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PD-1 inhibitor

Arm Description

Neoadjuvant therapy with PD-1 inhibitor (Toripalimab)

Outcomes

Primary Outcome Measures

Pathological complete remission (pCR) rates
Percentage of patients who achieve pathological complete remission (pCR)

Secondary Outcome Measures

R0 resection rates
The proportion of patients experiencing a R0 resection
three-year disease-free survival rate, DFS
Percentage of patients who achieve disease-free survival lasting for more than three years
three-year Overall survival rate,OS
Percentage of patients who achieve survival for more than two years
Incidence of Treatment-Related Adverse Events
Number of adverse events.

Full Information

First Posted
August 9, 2023
Last Updated
August 9, 2023
Sponsor
Sun Yat-sen University
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1. Study Identification

Unique Protocol Identification Number
NCT05994456
Brief Title
Neoadjuvant Toripalimab for dMMR/MSI-H Gastric Cancer
Official Title
Neoadjuvant Toripalimab in the Treatment of Locally Advanced dMMR/MSI-H Gastric or Gastroesophageal Junction Adenocarcinoma:an Open-label, Single-arm,Multi-center,Phase II Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 9, 2023 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen 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
This is a single-center, open phase II clinical trial to evaluate the tolerability, safety and efficacy of toriparib monotherapy in the treatment of locally advanced dMMR/MSI-H gastric or gastroesophageal junction adenocarcinoma.
Detailed Description
In this phase II study, eligible patients are enrolled to receive toripalimab 240mg, ivdrip, Q3W to evaluate the anti-tumor efficacy and safety. After 2 and 4 cycles of toripalimab treatment, tumors are assessed, and patients are assigned to receive surgery or withdraw from study according to their anti-tumor efficacy. For patients withdrawing from study, routine treatment would be given. For patients staying in study, toripalimab would be administered for up to 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric or Gastroesophageal Junction Adenocarcinoma
Keywords
dMMR/MSI-H, Gastric cancer

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
PD-1 inhibitor
Arm Type
Experimental
Arm Description
Neoadjuvant therapy with PD-1 inhibitor (Toripalimab)
Intervention Type
Drug
Intervention Name(s)
PD-1 inhibitor
Other Intervention Name(s)
Toripalimab
Intervention Description
240mg, Q3W. The opportunity for surgery was evaluated after 2 cycles of treatment and surgical treatment was performed after 2-4 cycles of treatment. Postoperatively, adjuvant therapy was continued according to the neoadjuvant regimen, and direct treatment met the criteria for termination of treatment.
Primary Outcome Measure Information:
Title
Pathological complete remission (pCR) rates
Description
Percentage of patients who achieve pathological complete remission (pCR)
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
R0 resection rates
Description
The proportion of patients experiencing a R0 resection
Time Frame
12 weeks
Title
three-year disease-free survival rate, DFS
Description
Percentage of patients who achieve disease-free survival lasting for more than three years
Time Frame
3 years
Title
three-year Overall survival rate,OS
Description
Percentage of patients who achieve survival for more than two years
Time Frame
3 years
Title
Incidence of Treatment-Related Adverse Events
Description
Number of adverse events.
Time Frame
3 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: 1. Aged 18-75 years, regardless of gender 2. Patients with histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction and confirmed dMMR or MSI-H 3. Preoperative CT or MRI staging meeting the following criteria: T2 and above, with or without lymph node involvement, without clear distant metastasis 4. ECOG score of 0-1. 5. Expected survival ≥ 2 years. 6. Good organ function (no blood transfusion, no hematopoietic stimulating factor, no albumin or blood product transfusion within 14 days prior to the examination). Platelet (PLT) count ≥ 90*109/L. Neutrophil count (ANC) ≥ 1.5*109/L. Hemoglobin (Hb) level ≥ 9.0 g/dl. International normalized ratio (INR) ≤ 1.5. Prothrombin time (PT) and active partial thromboplastin time (APTT) ≤ 1.5 x ULN. Glycated hemoglobin (HbA1c) <7.5%. Total bilirubin (TBIL) level ≤ 1.5 times the upper limit of normal (ULN). Alanine amino transaminase (ALT) and aspartate amino transaminase (AST) levels ≤ 2.5 x ULN. Serum creatinine (Cr) level ≤ 1.5 x ULN and creatinine clearance ≥ 60 ml/min. Thyrotropin (TSH) ≤ ULN; serum free thyroid hormone (T4) normal; serum free triiodothyronine (T3) normal; (except for those who have received previous thyroid surgery or have a history of head and neck radiotherapy) Serum amylase ≤ 1.5 x ULN. Lipase ≤ 1.5×ULN. 7. Women of childbearing age must have a negative pregnancy test and must use contraception and avoid breastfeeding during the study and for 3 months after the last dose; male subjects must agree to use contraception during the study and for 3 months after the last dose. 8.Be able to understand and willing to sign a written informed consent form. Exclusion Criteria: Previously received chemotherapy, radiotherapy or immunotherapy for gastric cancer Previously diagnosed any other malignancy with a primary site or histological type different from gastric cancer within 5 years prior to study entry, except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix With known hypersensitivity to the study drug or excipients, or to similar drugs Received major surgery or open biopsy, or had a major trauma within 4 weeks prior to the start of study treatment Received immunosuppressive drugs (excluding inhaled corticosteroids or ≤10 mg/day prednisone or equivalent pharmacophysiologic doses of other systemic steroids) within 2 weeks prior to the start of study treatment Planned live attenuated vaccination within 4 weeks prior to the start of study treatment or during the study period Inability to discontinue CYP3A4 inducers or inhibitors within 1 week prior to the start of study treatment and during the study period Presence of any autoimmune disease or history of autoimmune disease. Human immunodeficiency virus (HIV) infection (HIV antibody positive), or active hepatitis C virus (HCV) infection (HCV antibody positive), or active hepatitis B virus (HBV) infection (HBsAg positive and HBV-DNA ≥ 2000 IU/ml copies/ml)), or other serious infection requiring antibiotics for systemic therapy, or during screening/study Unexplained temperature >38.5°C prior to the start of treatment. Presence of the following diseases within 6 months prior to the start of study treatment: myocardial infarction, severe/unstable angina, NYHA class 2 or higher congestive heart failure, poorly controlled arrhythmias, etc. Non-well-controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg under optimal treatment) Arterial/venous thrombotic events such as cerebrovascular accidents (transient ischemic attack, cerebral hemorrhage, cerebral infarction, etc.), deep vein thrombosis, vasculitis, etc. within 3 months prior to the start of study treatment Urine routine suggesting urine protein up to +++ and confirmed 24-hour urine protein quantification up to 1.0g. The presence of a history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation Seizures requiring medication (e.g., steroids or antiepileptic drugs) for treatment. Presence of a history of substance abuse, drug use, or alcohol dependence. Patients with other serious, acute or chronic medical conditions that may increase the risk of study participation and study medication, or that may interfere with the interpretation of study results, and who are judged by the investigator to be unsuitable for participation in a clinical trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dongsheng Zhang, PhD
Phone
86-2087343795
Email
zhangdsh@sysucc.org.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dongsheng Zhang, PhD
Organizational Affiliation
Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dongsheng Zhang, Dr.
Phone
+8602087343560
Email
zhangds@sysucc.org.cn
First Name & Middle Initial & Last Name & Degree
Zhang

12. IPD Sharing Statement

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Neoadjuvant Toripalimab for dMMR/MSI-H Gastric Cancer

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