Sintilimab Combined With Modified FLOT Regimen in the Treatment of Metastatic Gastric Cancer

August 1, 2023 updated by: Weijian Guo, Fudan University

PD-1 Antibody Sintilimab Combined With Modified FLOT Regimen in the Treatment of Metastatic Gastric Cancer: a Phase II Clinical Study

This is a prospective, one-arm, single-center phase II study. The objective was to evaluate the efficacy and safety of domestic PD-1 antibody Sintilimab combined with modified FLOT regimen in the treatment of metastatic gastric cancer. To compare the time of maintenance of treatment after induction of chemotherapy with sintilimab combined with modified FLOT regimen until the reapplication of induction regimen with or without the combination of sintilimab, and the time of secondary progression after signing informed consent until the reapplication of induction regimen with or without the combination of sintilimab.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study set up two cohorts, Cohort A: patients with HER2-negative advanced gastric cancer, and planned to enroll 87 patients with initially treated advanced gastric cancer. Thirty patients with ORR of more than 70% were enrolled in the first stage and then further enrolled. Cohort B: advanced gastric cancer patients with HER2 positive initial treatment, the number of enrolled is not specified. Patients with initially treated advanced gastric cancer who meet the inclusion criteria will be enrolled in this study to receive Sintilimab combined with mFLOT regimen. Trastuzumab was given to Cohort B. The results were repeated every 2 weeks and evaluated every 6 weeks. The examination methods were consistent with those at baseline. Patients without disease progression were treated for a maximum of 6 cycles, then switched to oral capecitabine monotherapy combined with the sintilimab until disease progression, intolerable adverse reactions, patient death, or withdrawal of informed consent. If intolerability toxicity of albumin paclitaxel or oxaliplatin occurs within 6 cycles, maintenance is advanced to sintilimab combined with capecitabine monotherapy. Patients were randomly assigned to Cohort A1 and Cohort A2 after maintaining treatment progress. Cohort A1: Cohort 1 combined with mFLOT; Cohort A2: mFLOT program Therapy. The regimen was repeated every 2 weeks and tumor efficacy was evaluated every 3 treatment cycles. Patients without disease progression were treated for a maximum of 6 cycles before being switched to monotherapy S-1 oral with or without sintilimab until disease progression, intolerable adverse reactions, patient death, or withdrawal of informed consent. The treatment should start within 1 week after the signing of informed consent, and the time from the signing of informed consent to the first progress should be PFS1; The time from the signing of informed consent to the progress of induction program back to the second progress is PFS2. In this study, peripheral blood and tissue samples of patients will be collected to analyze the correlation between biomarkers (such as Micro-RNA, cytokine expression levels, etc.) and efficacy and prognosis. The expected time of enrollment was 48 months, and the patients were observed clinically until disease progression and death. (PFS2 equals PFS1 if the induction regimen is applied again after the first disease progression and the first efficacy evaluation is the disease progression)

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
87

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Xiaodong Zhu, M.D.,Ph.D.
  • Phone Number: 64175590
  • Email: xddr001@163.com

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Recruiting
        • Fudan University Shanghai Cancer Center
        • Contact:

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Aged ≥18 years and men or women
  2. With histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction, local lesions that cannot be radically resected, or metastatic gastric cancer
  3. For treatment-naïve patients, or postoperative recurrence at least 6 months from the last adjuvant chemotherapy
  4. With Eastern Cooperative Oncology Group (ECOG) PS of 0-1
  5. With a life expectancy of more than 3 months
  6. Who obtain the following laboratory test data within 7 days (including the seventh day) prior to the study screening: neutrophil count of ≥1.5 × 10^9/L, platelet count of ≥100 × 10^9/L, hemoglobin level of ≥90 g/L, serum total bilirubin of ≤1.25 the upper limit of normal (ULN); ALT and AST levels of ≤2.5 × ULN (≤5 × ULN for patients with liver metastasis); serum creatinine level of ≤1.0 × ULN and creatinine clearance of ≥50 ml/min; International Normalized ratio (INR) or prothrombin time (PT) ≤1.5 ULN; If the subject is receiving anticoagulant therapy, PT should be within the prescribed anticoagulant range.
  7. With at least one extragastric measurable lesion (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria)
  8. Patients (or their legal representative/guardian) must sign an informed consent form indicating that they understand the purpose of the study, understand the procedures necessary for the study, and are willing to participate in the study.

Exclusion Criteria:

  1. Patients with history of other types of cancer in the last 3 years, except for cured cervical cancer or cutaneous basal cell carcinoma.
  2. Patients with symptomatic brain or leptomeningeal metastases (unless the patient has been treated for >2 months) who has a negative imaging result within 4 weeks before participating in the study and is stable disease at study entry.
  3. Patients with clinically significant gastrointestinal obstruction, gastrointestinal bleeding (defecate occult blood + + + and above) or perforation.
  4. Patients who have received PD-1, PD-L1 or PD- L2, CD137, CTLA-4 antibody therapy, or any other T cells stimulate or total checkpoint pathways for specific target antibody or drugs.
  5. Patients with active, or have a history and possible recurrence of autoimmune disease of the subjects (such as: Systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.), or those at high risk (such as those who have received an organ transplant requiring immunosuppressive therapy). However, patients with vitiligo, psoriasis, alopecia, or Grave's disease who did not require systemic treatment within the last 2 years, or patients with hypothyroidism who required only thyroid hormone replacement therapy, and patients with type 1 diabetes who required only insulin replacement therapy could be enrolled.
  6. Patients now with interstitial lung disease or pneumonia, pulmonary fibrosis, acute lung diseases, radiation pneumonia.
  7. Patients who received any investigational drugs or antitumor drugs within 4 weeks prior to enrollment.
  8. Patients who received immunosuppressive drugs within 4 weeks, which does not include nasal, inhalation or other routes of topical corticosteroids or physiological doses of systemic corticosteroids (i.e., not exceeding 10 mg/ day of prednisone or equivalent doses of other corticosteroids), or short-term (not exceeding 7 days) use of corticosteroids for the prevention or treatment of non-autoimmune allergic diseases.
  9. Patients who received the live attenuated vaccine within 4 weeks before the first dose of study treatment. Note: Inactivated virus vaccines for injectable seasonal influenza are permitted for up to 4 weeks prior to initial administration; But live attenuated influenza vaccines are not allowed;
  10. Patients who received major surgery within 4 weeks before the first dose of study treatment(open chest, craniotomy or laparotomy) or expected during the research and treatment need to accept major surgery not associated with this study.
  11. Patients who infected with human immunodeficiency virus (HIV) disease (HIV antibody positive), or with other acquired, congenital immunodeficiency disease, or has a history of organ transplantation, or stem cell transplantation.
  12. Patients who have chronic active hepatitis B or active active hepatitis C. Hepatitis B virus carriers, stable after drug treatment of hepatitis B (DNA drop degree is not higher than 200 iu/mL or copy number < 1000 copies/mL) and has cured patients with hepatitis c (HCV RNA test negative) into the group.
  13. Patients with known active tuberculosis.
  14. Patients with severe infections before 4 weeks of fisrt dose of treatment, active infection which needs oral or intravenous antibiotic therapy before 4 weeks of fisrt dose of treatment.
  15. Patients with symptomatic congestive heart failure (New York heart association grade II - IV) or symptomatic or poorly controlled arrhythmia.
  16. Patiemts with uncontrolled arterial blood pressure with specification treatment (systolic blood pressure of greater than 160mmHg or diastolic blood pressure of greater than 100 mmHg).
  17. Patients who had any arterial thromboembolic events, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack within 6 months before the screening.
  18. Patinets with deep vein thrombosis, pulmonary embolism, or any other serious history of thromboembolism within 3 months (implantable venous infusion port source sex or catheter thrombosis, or superficial venous thrombosis were not regarded as a "severe" thromboembolism).
  19. Patients who have a history of neurological or psychiatric disorders, such as memory, epilepsy, dementia, compliance, or the peripheral nervous system disorder.
  20. alcohol dependence or 1-year history of drug or drug abuse.
  21. Pregnancy or lactation women; Those who are fertile but do not take adequate contraceptive measures;
  22. may lead to the following results of other acute or chronic diseases, mental illness or abnormal laboratory values: participated in or study drug dosage associated with an increased risk, or interfere with the interpretation of results, and according to the researcher's judgment does not conform the patient to participate in this study.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Nab-POF
Sintilimab 200mg d1 ivgtt+paclitaxel-albumin 125mg/m2 d1 ivgtt+oxaliplatin 85mg/m2 d1 ivgtt+5-FU 2.4g/m2 civ46h, q2w.
Drug: Sintilimab, paclitaxel-albumin, oxaliplatin, 5-FU
The study has only one arm. Sintilimab 200mg d1 ivgtt+paclitaxel-albumin 125mg/m2 d1 ivgtt+oxaliplatin 85mg/m2 d1 ivgtt+5-FU 2.4g/m2 civ46h, q2w.
Other Names:
  • Sintilimab+mFLOT

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression-Free survival 2, PFS2
Time Frame: From date of informed consent to time of secondary progression, assessed up to 60 months
From date of informed consent to time of secondary progression
From date of informed consent to time of secondary progression, assessed up to 60 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall survival, OS
Time Frame: the period from the date of randomization to the date of death from any cause, assessed up to 60 months
the period from the date of randomization to the date of death from any cause.
the period from the date of randomization to the date of death from any cause, assessed up to 60 months
Objective response rate
Time Frame: Baseline, Every 6 weeks during the procedure, up to 1 year. After 1 year, every 3 months.
the proportion of patients whose tumor dcrease to a certain size and remained for a certain period of time, including those with complete response(CR) and partial response (PR).
Baseline, Every 6 weeks during the procedure, up to 1 year. After 1 year, every 3 months.
Progression-Free survival 1, PFS1
Time Frame: From date of informed consent to time of first progression, assessed up to 60 months.
From date of informed consent to time of first progression
From date of informed consent to time of first progression, assessed up to 60 months.
After Effects
Time Frame: Baseline, Every cycle of treatment, until disease progression or death, whichever come first.
CTC AE Version 5.0 will be used to evaluate the clinical safety of the treatment in the study.
Baseline, Every cycle of treatment, until disease progression or death, whichever come first.

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fudan University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: WeiJian Guo, M.D.,Ph.D., Fudan University

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 9, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 19, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 1, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 8, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 8, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 1, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • FDZL-PFMG

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

We plan to share IPD after the publication of the study.

IPD Sharing Time Frame

We plan to share IPD after the publication of the study.

IPD Sharing Access Criteria

Data sharing requires approval from the principal investigator.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

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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