search
Back to results

Clinical Efficacy in Neoadjuvant Treatment of Locally Advanced Gastric Cancer With Different Immunotypes

Primary Purpose

Locally Advanced Gastric Cancer

Status
Not yet recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Camrelizumab
Albumin Taxol
FLOT scheme
Sponsored by
Fujian Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced Gastric Cancer

Eligibility Criteria

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

Inclusion Criteria: 1. Age from 18 to 75 years, all sex; 2. Primary gastric adenocarcinoma (papillary, tubular, mucinous, signet ring cell, or poorly differentiated) confirmed pathologically by histology or cytology; 3. CT/MRI,PET-CT or laparoscopic exploration were used to confirm the diagnosis of gastric cancer staging as cT2-4a and/or N+ and M0 before operation.; 4. Measurable lesions at least should be detected by CT/MRI examination in accordance with the RECIST1.1.(CT scan of tumor lesion length≥10mm,CT scan short diameter of lymph node≥15mm,scan slice thickness 5mm); 5. ECOG(Eastern Cooperative Oncology Group) PS(Performance Status):0-1 scores; 6. The expected survival time is more than 12 weeks; 7. The main organ function is normal, which should meet the following criteria: blood routine examination standards should be met(no blood transfusion within 14 days) HB≥100g/L, WBC≥3×109/L ANC≥1.5×109/L, PLT≥100×109/L; biochemical examination shall comply with the following criteria: BIL <1.5normal upper limit(ULN), ALT和AST<2.5ULN,GPT≤1.5×ULN; serum Cr≤1ULN,creatinine clearance rate>60ml/min(Cockcroft-Gault formula) 8. women of childbearing age must have a pregnancy test in 7 days before entering the group (in serum), and the results were negative, and willing to use appropriate contraception during the study period and the last 8 weeks after giving drug; men should have the surgical sterilization, or adopt the appropriate contraceptive methods during the test and the last 8 weeks after giving drug.; 9. No other clinical studies were conducted before and during the treatment; participants is willing to participate in this study, sign the informed consent, have good compliance, cooperate with follow-up. Exclusion Criteria: Previous history of chemotherapy, radiotherapy, targeted drug therapy or immunotherapy Patients with contraindications for surgical treatment and chemotherapy or whose physical condition and organ function do not allow for major abdominal surgery; Patients with metastasis; Having any active autoimmune diseases or a history of autoimmune diseases (such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); Patients with vitiligo or cured childhood asthma/allergies who did not need any intervention in adulthood were excluded; Autoimmune hypothyroidism treated with a stable dose of thyroid replacement hormone; Type 1 diabetes with stable doses of insulin; A history of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency disorders, or a history of organ transplantation and allogeneic bone marrow transplantation; Accompanied by serious heart, lung, liver, kidney disease; Have nerve, mental disease; Jaundice or obstruction of the digestive tract with severe infection; Pregnant or lactating women; The blood pressure of patients with hypertension cannot be reduced to the normal range by the antihypertensive drugs (systolic pressure >140 mmHg, diastolic pressure >90 mmHg); With Ⅰ magnitude of coronary heart disease, arrhythmia (including QTc protracted between male > 450 ms, women > 470 ms) and cardiac insufficiency; Patients have a clear tendency with gastrointestinal bleeding, including the following situation: local active ulcerative lesions, and fecal occult blood (+ +); with melena and hematemesis history in 2 months; and patients with fecal occult blood (+) and coagulation dysfunction (INR(international normalized ratio)>1.5, APTT(activated partial thromboplastin time)>1.5 ULN), with bleeding tendency;; Subjects have failed to control good cardiovascular clinical symptoms or disease, including but not limited to: such as: (1) the NYHA class II heart failure or above (2) unstable angina pectoris (3) MI occurred within 1 year (4) have clinical significance of supraventricular or ventricular arrhythmias without clinical intervention on or after clinical intervention is still poorly controlled; History of interstitial lung disease (except radiation pneumonia without hormone therapy), and history of non-infectious pneumonia; Patients are positive of urine protein (urine protein detection 2+ or above, or 24 hours urine protein quantitative >1.0g); A person who has previously been allergic to any component of the drug in this study; The researchers consider those who were not suitable for inclusion.

Sites / Locations

  • Fujian Medical University Union Hospital
  • Department of Gastric Surgery

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Arm Label

Immune activated experimental group

Immune activated control group

Immune silence experimental group

Immunosilent control group

Arm Description

Albumin paclitaxel 260mg/m2, ivgtt, d1, d8 Carrelizumab: 200mg, ivgtt, d1, q3w

Docetaxel 50mg/m2, ivgtt, d1, q14d; Oxaliplatin 85mg/m2, ivgtt, d1, q14d; Calcium folinate 200mg/m2, ivgtt, d1, q14d; 5-fluorouracil 2600mg/m2, 24h civ, d1, q14d

Carrelizumab: 200mg, ivgtt, d1, q3w Docetaxel 50mg/m2, ivgtt, d1, q14d; Oxaliplatin 85mg/m2, ivgtt, d1, q14d; Calcium folinate 200mg/m2, ivgtt, d1, q14d; 5-fluorouracil 2600mg/m2, 24h civ, d1, q14d

Docetaxel 50mg/m2, ivgtt, d1, q14d; Oxaliplatin 85mg/m2, ivgtt, d1, q14d; Calcium folinate 200mg/m2, ivgtt, d1, q14d; 5-fluorouracil 2600mg/m2, 24h civ, d1, q14d

Outcomes

Primary Outcome Measures

Objective response rate
Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST) version. 1.1, and immune-related (ir) RECIST

Secondary Outcome Measures

R0 resection rate
The surgical procedure was total or subtotal gastrectomy with 3 weeks after total neoadjuvant therapy
Disease control rate
Disease control rate
1-year and 3-year OS
1-year and 3-year OS
1-year and 3-year DFS
1-year and 3-year DFS
Adverse event
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Overall postoperative morbidity rates
Refers to the incidence of early postoperative complications. The early postoperative complication are defined as the event observed within 30 days after surgery
30 days mortality rates
Defined as the event observed within 30 days after surgery
Duration of postoperative hospital stay
Duration of postoperative hospital stay in days is used to assess the postoperative recovery course
The prediction performance of Exosome contents (including proteins, nucleic acids)
Exosomes were isolated using a Backman Optima XPN-100 instrument. The exosomes morphology was characterized using a HT7700 transmission electron microscope (Hitachi, Co. Ltd., Japan). Fluorescent spectra were recorded using a F96 Pro fluorospectrophotometer (Shanghai Lengguang Technology). The concentration and size distribution of the exosomes were quantified using nanoparticle tracking analysis (NanoSight NS 300, Malvern Instrument). The obtained results were subjected to biostatistical analysis, such as heat map generation, ROC curve establishment, and confusion matrix.

Full Information

First Posted
October 6, 2022
Last Updated
November 8, 2022
Sponsor
Fujian Medical University
search

1. Study Identification

Unique Protocol Identification Number
NCT05610332
Brief Title
Clinical Efficacy in Neoadjuvant Treatment of Locally Advanced Gastric Cancer With Different Immunotypes
Official Title
Clinical Efficacy of Albumin Paclitaxel Plus Carrelizumab Versus FLOT in Neoadjuvant Treatment of Locally Advanced Gastric Cancer With Different Immunotypes--A Multi-center, Randomised, Open, Phase 3 Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 1, 2022 (Anticipated)
Primary Completion Date
November 1, 2024 (Anticipated)
Study Completion Date
November 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fujian Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To evaluate the clinical efficacy of albumin paclitaxel combined with carelizumab and FLOT in the neoadjuvant treatment of locally advanced gastric cancer with different immune types
Detailed Description
Background: At present, there is still a lack of prospective data to systematically compare the clinical efficacy of different neoadjuvant therapies in patients with different genotypes. To explore the clinical efficacy and safety of albumin paclitaxel combined with carrelizumab compared with FLOT neoadjuvant therapy in patients with locally advanced gastric cancer of different immune types. Methods: This study is a multi center prospective study. 216 patients with gastric adenocarcinoma were included in the study to explore the proportion of PD-L1 positive cells in tumor tissue, evaluate the expression of PD-L1, serum HBV DNA level or other biomarkers.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Gastric Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
216 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Immune activated experimental group
Arm Type
Experimental
Arm Description
Albumin paclitaxel 260mg/m2, ivgtt, d1, d8 Carrelizumab: 200mg, ivgtt, d1, q3w
Arm Title
Immune activated control group
Arm Type
Active Comparator
Arm Description
Docetaxel 50mg/m2, ivgtt, d1, q14d; Oxaliplatin 85mg/m2, ivgtt, d1, q14d; Calcium folinate 200mg/m2, ivgtt, d1, q14d; 5-fluorouracil 2600mg/m2, 24h civ, d1, q14d
Arm Title
Immune silence experimental group
Arm Type
Experimental
Arm Description
Carrelizumab: 200mg, ivgtt, d1, q3w Docetaxel 50mg/m2, ivgtt, d1, q14d; Oxaliplatin 85mg/m2, ivgtt, d1, q14d; Calcium folinate 200mg/m2, ivgtt, d1, q14d; 5-fluorouracil 2600mg/m2, 24h civ, d1, q14d
Arm Title
Immunosilent control group
Arm Type
Active Comparator
Arm Description
Docetaxel 50mg/m2, ivgtt, d1, q14d; Oxaliplatin 85mg/m2, ivgtt, d1, q14d; Calcium folinate 200mg/m2, ivgtt, d1, q14d; 5-fluorouracil 2600mg/m2, 24h civ, d1, q14d
Intervention Type
Drug
Intervention Name(s)
Camrelizumab
Intervention Description
Camrelizumab One course will last 21 days. Given once every 3 weeks at a dose of 200 mg.
Intervention Type
Drug
Intervention Name(s)
Albumin Taxol
Intervention Description
Albumin paclitaxel was administered intravenously (without pretreatment) for 30 min on the first day of each cycle
Intervention Type
Drug
Intervention Name(s)
FLOT scheme
Intervention Description
Docetaxel 50mg/m2, ivgtt, d1; Oxaliplatin 85 mg/m2, ivgtt, d1; Calcium folinate 200mg/m2, ivgtt, d1; 5-fluorouracil 2600mg/m2, 24h civ, d1, 4 cycles before and after operation, q2w
Primary Outcome Measure Information:
Title
Objective response rate
Description
Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST) version. 1.1, and immune-related (ir) RECIST
Time Frame
4 months
Secondary Outcome Measure Information:
Title
R0 resection rate
Description
The surgical procedure was total or subtotal gastrectomy with 3 weeks after total neoadjuvant therapy
Time Frame
4 months
Title
Disease control rate
Description
Disease control rate
Time Frame
4 months
Title
1-year and 3-year OS
Description
1-year and 3-year OS
Time Frame
1 and 3 years
Title
1-year and 3-year DFS
Description
1-year and 3-year DFS
Time Frame
1 and 3 years
Title
Adverse event
Description
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time Frame
3 years
Title
Overall postoperative morbidity rates
Description
Refers to the incidence of early postoperative complications. The early postoperative complication are defined as the event observed within 30 days after surgery
Time Frame
30 days
Title
30 days mortality rates
Description
Defined as the event observed within 30 days after surgery
Time Frame
30 days
Title
Duration of postoperative hospital stay
Description
Duration of postoperative hospital stay in days is used to assess the postoperative recovery course
Time Frame
30 days
Title
The prediction performance of Exosome contents (including proteins, nucleic acids)
Description
Exosomes were isolated using a Backman Optima XPN-100 instrument. The exosomes morphology was characterized using a HT7700 transmission electron microscope (Hitachi, Co. Ltd., Japan). Fluorescent spectra were recorded using a F96 Pro fluorospectrophotometer (Shanghai Lengguang Technology). The concentration and size distribution of the exosomes were quantified using nanoparticle tracking analysis (NanoSight NS 300, Malvern Instrument). The obtained results were subjected to biostatistical analysis, such as heat map generation, ROC curve establishment, and confusion matrix.
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. Age from 18 to 75 years, all sex; 2. Primary gastric adenocarcinoma (papillary, tubular, mucinous, signet ring cell, or poorly differentiated) confirmed pathologically by histology or cytology; 3. CT/MRI,PET-CT or laparoscopic exploration were used to confirm the diagnosis of gastric cancer staging as cT2-4a and/or N+ and M0 before operation.; 4. Measurable lesions at least should be detected by CT/MRI examination in accordance with the RECIST1.1.(CT scan of tumor lesion length≥10mm,CT scan short diameter of lymph node≥15mm,scan slice thickness 5mm); 5. ECOG(Eastern Cooperative Oncology Group) PS(Performance Status):0-1 scores; 6. The expected survival time is more than 12 weeks; 7. The main organ function is normal, which should meet the following criteria: blood routine examination standards should be met(no blood transfusion within 14 days) HB≥100g/L, WBC≥3×109/L ANC≥1.5×109/L, PLT≥100×109/L; biochemical examination shall comply with the following criteria: BIL <1.5normal upper limit(ULN), ALT和AST<2.5ULN,GPT≤1.5×ULN; serum Cr≤1ULN,creatinine clearance rate>60ml/min(Cockcroft-Gault formula) 8. women of childbearing age must have a pregnancy test in 7 days before entering the group (in serum), and the results were negative, and willing to use appropriate contraception during the study period and the last 8 weeks after giving drug; men should have the surgical sterilization, or adopt the appropriate contraceptive methods during the test and the last 8 weeks after giving drug.; 9. No other clinical studies were conducted before and during the treatment; participants is willing to participate in this study, sign the informed consent, have good compliance, cooperate with follow-up. Exclusion Criteria: Previous history of chemotherapy, radiotherapy, targeted drug therapy or immunotherapy Patients with contraindications for surgical treatment and chemotherapy or whose physical condition and organ function do not allow for major abdominal surgery; Patients with metastasis; Having any active autoimmune diseases or a history of autoimmune diseases (such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); Patients with vitiligo or cured childhood asthma/allergies who did not need any intervention in adulthood were excluded; Autoimmune hypothyroidism treated with a stable dose of thyroid replacement hormone; Type 1 diabetes with stable doses of insulin; A history of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency disorders, or a history of organ transplantation and allogeneic bone marrow transplantation; Accompanied by serious heart, lung, liver, kidney disease; Have nerve, mental disease; Jaundice or obstruction of the digestive tract with severe infection; Pregnant or lactating women; The blood pressure of patients with hypertension cannot be reduced to the normal range by the antihypertensive drugs (systolic pressure >140 mmHg, diastolic pressure >90 mmHg); With Ⅰ magnitude of coronary heart disease, arrhythmia (including QTc protracted between male > 450 ms, women > 470 ms) and cardiac insufficiency; Patients have a clear tendency with gastrointestinal bleeding, including the following situation: local active ulcerative lesions, and fecal occult blood (+ +); with melena and hematemesis history in 2 months; and patients with fecal occult blood (+) and coagulation dysfunction (INR(international normalized ratio)>1.5, APTT(activated partial thromboplastin time)>1.5 ULN), with bleeding tendency;; Subjects have failed to control good cardiovascular clinical symptoms or disease, including but not limited to: such as: (1) the NYHA class II heart failure or above (2) unstable angina pectoris (3) MI occurred within 1 year (4) have clinical significance of supraventricular or ventricular arrhythmias without clinical intervention on or after clinical intervention is still poorly controlled; History of interstitial lung disease (except radiation pneumonia without hormone therapy), and history of non-infectious pneumonia; Patients are positive of urine protein (urine protein detection 2+ or above, or 24 hours urine protein quantitative >1.0g); A person who has previously been allergic to any component of the drug in this study; The researchers consider those who were not suitable for inclusion.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chang-Ming Huang, Ph.D.
Phone
8613805069676
Email
hcmlr2002@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Hua-long Zheng, Ph.D.
Phone
18359190587
Email
291167038@qq.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chang-Ming Huang, Ph.D.
Organizational Affiliation
Fujian Medical University Union Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fujian Medical University Union Hospital
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350000
Country
China
Facility Name
Department of Gastric Surgery
City
Fuzhou
State/Province
Fujian
Country
China

12. IPD Sharing Statement

Learn more about this trial

Clinical Efficacy in Neoadjuvant Treatment of Locally Advanced Gastric Cancer With Different Immunotypes

We'll reach out to this number within 24 hrs