A Multi-center, Two-arm, Phase 2 Clinical Study on the Perioperative Treatment of HER2-positive Resectable Esophagogastric Junctional Adenocarcinoma With Nabulimab Combined With FLOT and Trastuzumab VS FLOT Combined With Trastuzumab

November 6, 2024 updated by: xiaohua li
Patients with Her2+ resectable gastroesophageal conjunctive adenocarcinoma were randomly divided into observation group and control group. The observation group received preoperative nabuliumab combined with FLOT and trastuzumab + surgical treatment + postoperative nabuliumab combined with FLOT and trastuzumab. The control group was treated with preoperative FLOT combined with trastuzumab + surgical treatment + postoperative FLOT combined with trastuzumab. 4 cycles were performed before and after surgery in both groups, with one cycle every 2 weeks. The specific administration was docetaxel 50mg/m2 iv,d1, oxaliplatin 85mg/m2 iv,d1, calcium leucovorin 200mg/m2 iv,d1,5-FU 2600mg/m2 iv,d1, infusion 24h; Nebulizumab 240mg iv,d2, 30 minutes per intravenous infusion, trastuzumab 4mg/kg iv,d2 (load dose 6mg /kg). Surgical treatment was evaluated by the investigator within 3-4 weeks after the last dosing. After 4 cycles of adjuvant therapy, the observation group received nebuliumab combined with trastuzumab, while the control group received maintenance therapy with trastuzumab. Both groups received 10 cycles, one cycle every 2 weeks. The specific administration was as follows: nebuliuzumab 240mg iv,d1, 30 minutes per intravenous infusion; Trastuzumab 4mg/kg intravenously.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not 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 is a prospective, multicenter, randomized controlled clinical study. A total of 36 patients with locally advanced esophagogastric conjoint adenocarcinoma without any treatment and resection were included in this study. After signing informed consent and meeting the screening criteria, a total of 36 patients were randomized into the observation group and the control group (18 cases and 18 cases, respectively) without blindness. Other participants include the Second Affiliated Hospital of Air Force Medical University, Henan Provincial People's Hospital, Cancer Hospital of Tianjin Medical University, Zhongshan Hospital Affiliated to Shanghai Fudan University, and the First Affiliated Hospital of Xi 'an Jiaotong University. The research groups were as follows: patients with resectable gastroesophageal conjunctive adenocarcinoma were randomly divided into observation group and control group. The observation group received preoperative nabuliumab combined with FLOT and trastuzumab + surgical treatment + postoperative nabuliumab combined with FLOT and trastuzumab. The control group was treated with preoperative FLOT combined with trastuzumab + surgical treatment + postoperative FLOT combined with trastuall Zumab. Preoperative and postoperative cycles were 4 in both groups, with one cycle every 2 weeks. Specific administration was as follows: Docetaxel 50mg/m2 iv,d1, oxaliplatin 85mg/m2 iv,d1, calcium leucovorin 200mg/m2 iv,d1,5-FU 2600mg/m2 iv,d1, infusion 24h; Nebulizumab 240mg iv,d2, 30 minutes per intravenous infusion, trastuzumab 4mg/kg iv,d2 (load dose 6mg /kg). At 3-4 weeks after the completion of the last dosing cycle, the efficacy of neoadjuvant therapy and the possibility of radical resection were evaluated in combination with preoperative imaging examination, and radical surgical treatment was performed. After the operation, the investigator will determine whether to carry out adjuvant treatment and choose the appropriate treatment plan (the first treatment should start from 3-6W after the operation and should not exceed 3 months). After 4 cycles of adjuvant therapy, the observation group was treated with nebuliumab combined with trastuzumab, and the control group was treated with trastuzumab maintenance therapy, with 10 cycles for each The specific administration was as follows: 240mg iv,d1, intravenous infusion for 30 minutes each time; Trastuzumab 4mg/kg intravenously. Resection of esophagogastric junction carcinoma was performed based on the 2023 Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and treatment of gastric cancer.

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.
36

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 Locations

  • China
    • 陕西
      • Xi'an, 陕西, China, 710032
        • The First Affiliated Hospital of the Air Force Medical University

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. Age 18-75 years old;
  2. esophagogastric junction adenocarcinoma (including Siewert type I, Siewert type II, and Siewert type III) with histopathologic or cytological confirmation of HER2-positive (defined as positive immunohistochemical [IHC] greater than or equal to 2+ and fluorescence in situ hybridization [FISH]);
  3. The cTNM stages were cT3-4a, N+, M0 according to endoscopic ultrasound or enhanced CT/MRI scanning (combined with ultrasonic gastroscopy and diagnostic laparoscopic exploration if necessary) (refer to the 8th edition AJCCTNM staging system), and the lesions were resected as assessed by the investigator;
  4. Expected survival time > 6 months;
  5. ECOG PS score 0 or 1;
  6. PD-L1 does not require;
  7. No prior treatment;
  8. Hematological indexes were basically normal: white blood cell count ≥4×109/L; Absolute neutrophil count ≥1.5×109/L; Platelet ≥100×109/L; Hemoglobin ≥ 90 g/Lg/L;
  9. Basically normal renal function: serum creatinine ≤1.5×ULN or creatinine clearance (CrCl)>60 mL/min(using the Cockcroft-Gault formula);
  10. Basically normal liver function: serum total bilirubin ≤1.5×ULN; Aspartate aminotransferase (AST) ≤2.5×ULN; Alanine aminotransferase (ALT) ≤2.5×ULN;
  11. Female patients must have a negative urine pregnancy test before the start of the study (not applicable to patients with bilateral oophorectomy and/or hysterectomy or postmenopausal patients)
  12. Sign written informed consent.

Exclusion Criteria:

  • (1) No efficacy and/or safety evaluation has been performed; (2) The investigator believes that the patient is not suitable to continue (reasons for withdrawal should be recorded) (3) The patient requested that the trial be terminated; (4) Serious violation of protocol: participating in this study while using other anti-tumor drugs and/or modern Chinese medicine preparations with anti-cancer indications.

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 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: Nivolumab group
Preoperative nabuliumab combined with FLOT and trastuzumab + surgical treatment + postoperative nabuliumab combined with FLOT and trastuzumab. There were 4 cycles before and after surgery, one cycle every 2 weeks. The specific administration was: docetaxel 50mg/m2 iv,d1, oxaliplatin 85mg/m2 iv,d1, calcium leucovorin 200mg/m2 iv,d1,5-FU 2600mg/m2 iv,d1, infusion 24h; Nebulizumab 240mg iv,d2, 30 minutes per intravenous infusion, trastuzumab 4mg/kg iv,d2 (load dose 6mg /kg).
Drug: The experimental group received Nivolumab
Trastuzumab and the FLOT chemotherapy regimen are clearly recommended by guidelines, whereas Nivolumab is currently requiring further research validation.
Other Names:
  • Trastuzumab
  • FLOT
Active Comparator: Control group
The control group was treated with preoperative FLOT combined with trastuzumab + surgical treatment + postoperative FLOT combined with trastuzumab. Preoperative and postoperative cycles were 4 in both groups, with one cycle every 2 weeks. Specific administration was as follows: Docetaxel 50mg/m2 iv,d1, oxaliplatin 85mg/m2 iv,d1, calcium leucovorin 200mg/m2 iv,d1,5-FU 2600mg/m2 iv,d1, infusion 24h; Trastuzumab 4mg/kg iv,d2 (load dose 6mg /kg).
Drug: The experimental group received Nivolumab
Trastuzumab and the FLOT chemotherapy regimen are clearly recommended by guidelines, whereas Nivolumab is currently requiring further research validation.
Other Names:
  • Trastuzumab
  • FLOT

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
Pathological complete response rate (pCR)
Time Frame: 30 days
Pathological complete response rate refers to the proportion of primary tumor sites and surgical specimens with no viable tumor cells (ypT0N0) in all resected lymph nodes to the total number of patients evaluated centrally by the study pathologist
30 days

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
Objective response rate (ORR)
Time Frame: 30 days
Objective response rate (ORR) : ORR is the proportion of subjects who achieved partial and complete response on imaging assessment (RECIST v1.1) after the end of neoadjuvant therapy
30 days
Progression-free survival (PFS)
Time Frame: 1,3,5 years
Progression-free survival (PFS) : PFS is the time from the date of enrollment in the study to the date of death from all causes
1,3,5 years
Overall survival (OS)
Time Frame: 1,3,5 years
Overall survival (OS) : OS is the amount of time a patient can survive treatment without dying from any condition
1,3,5 years
Major pathological response rate (MPR)
Time Frame: 30 days
Major pathological response rate (MPR) : MPR refers to the proportion of patients with residual tumor cells < 10% after surgery to determine the pathological status of the primary lesion
30 days
Duration of response (DOR)
Time Frame: 5 years
Duration of response (DOR) : The DOR is the time from the first response until disease progression is first recorded or death occurs
5 years
Adverse Event Rate (AE)
Time Frame: 5 years
Adverse Event Rate (AE) : Any adverse events that may be related to the investigational drug that occur while receiving neoadjuvant therapy
5 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.
xiaohua li

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: Ruiqi Gao, Department of Gastrointestinal Surgery, Xijing Hospital, Fourth Military Medical 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.
May 1, 2024

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.
May 1, 2029

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.
May 1, 2029

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).
November 6, 2024

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.
November 6, 2024

First Posted (Estimated)

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.
November 8, 2024

Study Record Updates

Last Update Posted (Estimated)

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.
November 8, 2024

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.
November 6, 2024

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.
November 1, 2024

More Information

Terms related to this study

Keywords

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.
  • KY20242180-C-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Share in the form of an article or email

IPD Sharing Time Frame

start date :2024-5-1; finish date:2029-5-1.

IPD Sharing Access Criteria

Share in the form of an article or email(1073297317@qq.com)

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

product manufactured in and exported from the U.S.

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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