Fruquintinib Combined With Toripalimab and SOX Regimen in the First-line Treatment of Advanced Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

August 17, 2022 updated by: Feng Wang, The First Affiliated Hospital of Zhengzhou University

An Open Label, Single Arm, Multicenter Phase Ⅰb/Ⅱ Clinical Study of Fruquintinib Combined With Toripalimab and SOX Regimen in the First-line Treatment of Advanced Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

This is a prospective, open-label, multicenter, single arm phase Ⅰb/Ⅱ clinical study aims to explore the efficacy and safety of fruquintinib combined with toripalimab and SOX regimen in the first-line treatment of unresectable advanced metastatic gastric or gastroesophageal junction adenocarcinoma.

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

At present, the first-line standard treatment of metastatic gastric cancer is still doublet or triplet chemotherapy of fluorouracil combined with platinum or paclitaxel. In recent years, immune checkpoint inhibitors (ICIs) have emerged in advanced gastric cancer with their unique mechanism of action. PD-1 monoclonal antibody has been explored in multiple combination schemes in the first-line treatment of advanced gastric cancer. This study aims to explore the efficacy and safety of an antiangiogenetic TKI, fruquintinib combined with an ICI, toripalimab and the standard doublet SOX regimen in the first-line treatment of unresectable advanced metastatic gastric or gastroesophageal junction adenocarcinoma.

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 (Anticipated)

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.
64

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
  • Phase 1

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: Qingxia Fan, M.D.

Study Locations

  • China
    • Henan
      • Zhengzhou, Henan, China, 450052
        • Recruiting
        • The First Affiliated Hospital of Zhengzhou University
        • Contact:
          • Qingxia Fan, doctor

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

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Pathologically determined unresectable advanced gastric or gastroesophageal junction adenocarcinoma;
  • 18-75 years old (including 18 and 75 years old);
  • No previous anti-tumor treatment for metastatic diseases;
  • HER2 negative;
  • Eastern Cooperation Oncology Group (ECOG) performance status of 0-1;
  • Life expectancy ≥ 3 months;
  • At least one measurable lesion according to RECIST version 1.1;
  • Adequate organ and bone marrow functions:

Absolute neutrophil count≥1.5x10^9/L; Platelet count≥100x10^9/L; Hemoglobin≥9g/dL; Serum bilirubin≤1.5x the upper limit of normal(ULN); Alanine aminotransferase(ALT) and aspartate aminotransferase(AST)≤1.5x ULN; Serum creatinine≤1.5x ULN; Endogenous creatinine clearance rate ≥ 50ml / min;

  • Women of childbearing age need to take effective contraceptive measures.

Exclusion Criteria:

  • Previous treatment with vascular endothelial growth factor receptor (VEGFR) inhibitors or previous use of immune checkpoint inhibitors;
  • Other malignant tumors in the past 5 years, except for skin basal cell or squamous cell carcinoma after radical surgery, or cervical carcinoma in situ;
  • There was central nervous system (CNS) metastasis or previous brain metastasis before enrollment;
  • Patients with autoimmune diseases or history of autoimmune diseases within 4 weeks before enrollment;
  • Previously received allogeneic bone marrow transplantation or organ transplantation;
  • Uncontrolled malignant ascites;
  • Participated in other unapproved or unlisted drug clinical trials in China within 4 weeks before enrollment, and received corresponding experimental drug treatment;
  • Cardiovascular disease, including unstable angina or myocardial infarction, occurred within 6 months before the start of study treatment;
  • Subjects allergic to the study drug or any of its adjuvants;
  • International normalized ratio (INR) > 1.5 or partially activated prothrombin time (APTT) > 1.5 × ULN；
  • The researchers judged clinically significant electrolyte abnormalities;
  • At present, the patient has hypertension that cannot be controlled by drugs, which is specified as: systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg;
  • Patients currently have poorly controlled diabetes (fasting glucose level is greater than CTCAE grade 2 after regular treatment);
  • Patients with dysphagia, active peptic ulcer, intestinal obstruction, active gastrointestinal bleeding, peptic perforation, malabsorption syndrome or uncontrolled intestinal inflammatory diseases;
  • Any disease or state affecting drug absorption before enrollment, or the patient cannot take oral medication;
  • Patients with obvious evidence of bleeding tendency or medical history within 3 months before enrollment, hemoptysis or thromboembolism within 12 months;
  • Cardiovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe / unstable angina pectoris or coronary artery bypass grafting within 6 months before enrollment;
  • Ventricular arrhythmia requiring drug treatment;
  • Congestive heart failure ≤New York Heart Association (NYHA) class 2;
  • LVEF < 50%;
  • Active or uncontrolled severe infection ≥ grade 2 according to National Cancer Institute Common Toxicity (NCI-CTC) criteria;
  • With positive urine protein and 24-hour urinary protein content>1g;
  • Known human immunodeficiency virus (HIV) infection; known history of clinically significant liver disease, including viral hepatitis;
  • Pregnant (positive pregnancy test before medication) or lactating women;
  • Complications require long-term immunosuppressive treatment, or systemic or local use of immunosuppressive corticosteroids (> 10mg / day prednisone or other therapeutic hormones);
  • By judgment of the investigator, there are concomitant diseases that seriously endanger the safety of the patient or affect the completion of the 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: Experimental
fruquintinib + toripalimab + SOX
Drug: fruquintinib＋toripalimab + SOX
phase Ib: fruquintinib (dose finding): L1: 3 mg/d，L2: 4 mg/d，L3: 5 mg/d, qd po, D1-14, Q3W toripalimab: 240mg, I.V., D1, Q3W; S-1: 40-60mg bid, D1-14, Q3W; Oxaliplatin: 130mg/m^2, ivgtt 2h, D1,Q3W. phase II: fruquintinib: RP2D toripalimab: 240mg, I.V., D1, Q3W; S-1: 40-60mg bid, D1-14, Q3W; Oxaliplatin: 130mg/m^2, ivgtt 2h, D1,Q3W.

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
DLTs
Time Frame: At the end of Cycle 1 (each cycle is 28 days)
DLTs are defined as grade 3 or higher adverse events that are related to fruquintinib during the first cycle of therapy.
At the end of Cycle 1 (each cycle is 28 days)
RP2D
Time Frame: At the end of Cycle 1 (each cycle is 28 days)
Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)
At the end of Cycle 1 (each cycle is 28 days)
PFS
Time Frame: about 2 years
PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first.
about 2 years

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
OS
Time Frame: about 2 years
The time from treatment initiation until death from any reason
about 2 years
ORR
Time Frame: about 2 years
The proportion of patients with a confirmed complete response or partial response on two consecutive occasions≥4 weeks apart
about 2 years
DCR
Time Frame: about 2 years
The proportion of patients with a best overall response of confirmed complete or partial response, or stable disease (CR+ PR + SD)
about 2 years
DoR
Time Frame: about 2 years
Duration of Response is defined as the time from the first documentation of response (PR or better) to the first documented disease progression evidence (according to RECIST 1.1) of the responders
about 2 years
adverse events (AEs) categorized by severity in accordance with the NCI CTC AE Version 5.0
Time Frame: about 2 years
Safety and tolerance will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 5.0
about 2 years

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.
The First Affiliated Hospital of Zhengzhou 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.
June 1, 2022

Primary Completion (Anticipated)

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.
August 1, 2023

Study Completion (Anticipated)

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.
February 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).
August 20, 2021

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 25, 2021

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 27, 2021

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 18, 2022

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 17, 2022

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, 2022

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.
  • HMPL-013-FLAG-G102

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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