PD-1 Antibody Adjuvant Therapy for GC Patients With MSI-H After D2 Radical Surgery

August 24, 2022 updated by: Dazhi Xu, Fudan University

PD-1 Antibody Adjuvant Therapy for Patients With MSI-H Advanced Gastric or Gastroesophageal Junction Cancer After Radical Surgery With D2 Dissection: a Phase II Single-center, Three-arm, Randomized Controlled Clinical Trial

Approximately 5% to 10% of gastric cancers have MSI-H/dMMR. According to the results of retrospective analysis of CLASSIC and MAGIC, MSI-H/dMMR was a good prognosis and potential negative predictor of adjuvant chemotherapy for resectable gastric cancer. GC patients with MSI-H/dMMR were relatively insensitive to chemotherapy. The prognosis of these patients receiving routine postoperative adjuvant chemotherapy was worse than that with surgery alone. However, these patients were sensitive to immunotherapy. MSI-H/dMMR is one of the most important biomarkers to predict the efficacy of immunotherapy for GC. In this study, patients with MSI-H locally advanced gastric adenocarcinoma after radical surgery with D2 dissection would be randomly treated with conventional adjuvant chemotherapy, PD-1 monoclonal antibody immunotherapy or follow-up observation. We intend to demonstrate that the prognosis of MSI-H GC patients after D2 radical gastrectomy receiving PD-1 monoclonal antibody immunotherapy would be better than that with standard postoperative adjuvant chemotherapy and follow-up observation.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

We intend to demonstrate that the prognosis of MSI-H GC patients after D2 radical gastrectomy receiving PD-1 monoclonal antibody immunotherapy would be better than that with standard postoperative adjuvant chemotherapy and follow-up observation.

Study Type

Interventional

Enrollment (Anticipated)

141

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Shanghai, China
        • Dazhi Xu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Written (signed) informed consent;
  2. D2 radical gastrectomy for gastric cancer
  3. Postoperative pathology confirmed II-IIIc stage gastric adenocarcinoma with dMMR/MSI-H status;
  4. Female or male, 18-75 years;
  5. ECOG 0-1, no surgery contraindications;
  6. No initial treatment (radiotherapy / chemotherapy / immunotherapy).;
  7. Esophagus not involved ≥ 3cm;
  8. Basic diseases without thyroid and cardiopulmonary dysfunction
  9. Adequate hematological, liver, renal and coagulation function; 1) Platelet (PLT) count ≥100,000 /mm3; 2) Neutrophil count (ANC) ≥1,500 /mm3; 3) Hemoglobin (Hb) level ≥9.0 g/dl; 4) International normalized ratio (INR) ≤1.5; 5) Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5×ULN; 6) Glycosylated hemoglobin (HbA1c) <7.5%; 7) Total bilirubin (TBIL) level ≤1.5×ULN; 8) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level ≤2.5×ULN (≤5×ULN in case of liver metastasis); 9) Alkaline phosphatase level ≤2.5×ULN (≤5×ULN in case of liver metastasis); 10) Serum creatinine (Cr) level ≤1.5×ULN and creatinine clearance ≥60 ml/min; 11) Thyroid stimulating hormone (TSH) ≤ULN; 12) Normal serum free thyroid hormone (T4); 13) Normal serum free triiodothyronine (T3); 14) Serum amylase ≤1.5×ULN; 15) Lipase ≤1.5×ULN.
  10. Females of child bearing age must have a negative pregnancy test, and have to take contraception measures and avoid breast feeding during the study and for 3 months after the last dose; male subjects must agree to taken contraception measures during the study and for 3 months after the last dose.

Exclusion Criteria:

  1. Known allergy to study drug or excipients, or allergy to similar drugs;
  2. Patients with active malignant tumor in recent 2 years, except the tumor studied in this research or cured localized tumor like resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical or breast carcinoma in situ;
  3. Uncontrollable pleural effusion, pericardial effusion, or ascites in 2 weeks before recruitment;
  4. The patient has a serious history of heart disease, including congestive heart failure, uncontrollable arrhythmia, unstable angina pectoris, myocardial infarction, severe heart valve disease and intractable hypertension;
  5. Unable to swallow study drug;
  6. Prior chemotherapy, radiotherapy for gastric cancer;
  7. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent;
  8. Prior therapy with tyrosine kinase inhibitor within 2 weeks.
  9. Concurrent medical condition requiring the use of cortisol (>10mg/day Prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment. Except: inhalation or topical corticosteroids. Doses > 10 mg/day prednisone or equivalent for replacement therapy;
  10. Have vaccination with attenuated live vaccines within 4 weeks prior to initiation of the study treatment or plan to vaccinate during the study;
  11. Poorly controlled hypertension or diabetes;
  12. With bleeding tendency, or evident hemoptysis or other hemorrhagic events (e.g. gastrointestinal hemorrhage, hemorrhagic gastric ulcer) within 2 months prior to initiation of study treatment, or presence of hereditary or acquired bleeding or thrombotic tendency (e.g. hemophilia, coagulopathy, thrombocytopenia, etc.), or current/long-term thrombolytic or anticoagulant therapy (except aspirin ≤100 mg/day);
  13. Present or history of any autoimmune disease;
  14. With active tuberculosis or receiving previous anti-tuberculosis therapy within one year;
  15. Diagnosed with interstitial pneumonia, non-infectious pneumonia, pulmonary fibrosis, acute lung disease;
  16. Pregnancy or breast feeding;
  17. 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 or HBcAb positive, and HBV-DNA ≥2000 IU/ml (copies/ml)), or other severe infection requiring systemic antibiotic treatment, or unexplained body temperature >38.5℃ during screening period/before study treatment;
  18. Patients with other severe acute or chronic conditions that may increase the risk of participation in the study and study treatment, or may interfere with interpretation of study results, and judged by the investigator as not suitable for participation in this clinical trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Adjuvant chemotherapy(SOX or XELOX )

8 cycles of adjuvant SOX or XELOX should be performed within 8 weeks after receiving standard gastrectomy with D2 lymphadenectomy.

SOX: S-1：40~60mg bid，d1~14 q3W oxaliplatin：130mg/m2，iv drip for 2h，d1,q3W 8 cycles (6 months) XELOX: capecitabine：1000 mg/m2 ，bid, d1~14 q3W oxaliplatin：130mg/m2，iv drip for 2h，d1,q3W 8 cycles (6 months)
Drug: SOX

Drug: Tegafur-Gimeracil-Oteracil Potassium The dose of S-1 is according to body-surface area (BSA): patients with a BSA of less than 1.25 m2 received 80 mg daily; those with a BSA of 1.25 m2 or more but less than 1.5 m2 received 100 mg daily; and those with a BSA of 1.5 m2 or more received 120 mg daily. oxaliplatin 130mg/m2, intravenously, on day 1.

Drug: Oxaliplatin The dose of oxaliplatin is according to body-surface area (BSA): 130mg/m2, intravenously, on day 1.

Drug: XELOX
Drug: Capecitabine 1000mg/m2, orally, twice per day, from day 1 to day 14, Q3W. Drug: Oxaliplatin The dose of oxaliplatin is according to body-surface area (BSA): 130mg/m2, intravenously, on day 1.
EXPERIMENTAL: Observation
After receiving standard gastrectomy with D2 lymphadenectomy, regular follow-up every 3 months alone. Abdomen/chest CT scan will be performed every 6 months after surgery.
Other: Observation
follow up and Observation alone. Abdomen/chest CT scan will be performed every 6 months after surgery.
EXPERIMENTAL: PD-1 immunotherapy

Adjuvant treatment with PD-1 antibody every 3 weeks(maximum 1 years) should be performed within 8 weeks after receiving standard gastrectomy with D2 lymphadenectomy.

PD-1 antibody: Sintilimab at a dose of 200 mg every 3 weeks for 16 cycles or Nivolumab at a dose of 360 mg every 3 weeks for 16 cycles
Drug: PD-1 antibody
Sintilimab at a dose of 200 mg every 3 weeks for 16 cycles or Nivolumab at a dose of 360 mg every 3 weeks for 16 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
3 year Disease Free Survival
Time Frame: 3 years
3-year DFS
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
morbidity
Time Frame: 1 year
safety of PD1 antibody therapy
1 year
mortality
Time Frame: 1 year
safety of PD1 antibody therapy
1 year
adverse events during PD1 therapy
Time Frame: 1 year
safety of PD1 antibody therapy
1 year
5 year Overall Survival
Time Frame: 5 years
5-year OS
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

August 25, 2022

Primary Completion (ANTICIPATED)

December 31, 2025

Study Completion (ANTICIPATED)

December 31, 2025

Study Registration Dates

First Submitted

July 16, 2022

First Submitted That Met QC Criteria

July 20, 2022

First Posted (ACTUAL)

July 21, 2022

Study Record Updates

Last Update Posted (ACTUAL)

August 26, 2022

Last Update Submitted That Met QC Criteria

August 24, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PAMHG

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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