Gastric Cancer, Chemotherapy Effect
Conditions
Keywords
Neoadjuvant chemotherapy, perioperative chemotherapy, Systemic chemotherapy, FLOT, SOX, Gastric cancer
Brief summary
Safety and efficacy study of neoadjuvant chemotherapy (FLOT versus SOX) for gastric cancer patients in high volume center of China
Detailed description
DRAGON III research, Neoadjuvant Chemotherapy (FLOT versus SOX) for Gastric Cancer, is an investigator initiated; phase II, open label, randomised controlled study. This study will be conducted and analyzed by the Gastrointestinal department（Unit III）of the Ruijin Hospital and the project is supported by the Institute of Digestive Surgery, Shanghai, which is a state key research center. This study will be monitored by the Clinical Research Center of the Ruijin hospital (Official body which is responsible to guide and monitor all types of research at Ruijin hospital). Primary endpoint and secondary endpoint is described above. The aim of this study to obtain preliminary result and further conduct a large scale multi-center randomised controlled trial(RCT) study.
Interventions
5-FU+Leucovorin+Docetaxel+Oxaliplatin
DRUGSOX Chemotherapy
Oxaliplatin+Tegafur gimeracil oteracil potassium capsule (TGO)
Sponsors
Ruijin Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomly assigned(1:1) either to FLOT or SOX group.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Histology confirmed non-obstructive adenocarcinoma of the stomach or esophagogastric junction. * Clinical stage: cTNM: stage III or above * Performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 2 (normal to symptomatic but in bed less than half the day) * Clinically fit for systemic chemotherapy and gastric cancer surgery, i.e. adequate renal, hepatic, hematologic, and pulmonary function. * Written informed consent
Exclusion criteria
* Clinically unfit for systemic chemotherapy and gastric cancer surgery, i.e. uncontrolled cardiac disease, or other clinically significant uncontrolled comorbidities, unable to undergo general anesthesia * Confirmed distant metastases * Locally advanced inoperable disease (Clinical assessment) * Relapse of gastric cancer * Malignant secondary disease * Prior chemo or radiotherapy * Inclusion in another clinical trial * Known contraindications or hypersensitivity for planned chemotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Percentage of Patients With Pathological Complete Tumor Regression (TRG1a) and Sub-total Tumor Regression (TRG1b) in the Primary Tumour | Three months | Tumor regression grade (TRG), Becker criteria Grade 1a :Complete tumor regression: 0% residual tumor per tumor bed Grade 1b: Subtotal tumor regression: \<10% residual tumor per tumor bed Grade 2: Partial tumor regression: 10-50% residual tumor per tumor bed Grade 3: Minimal or no tumor regression: \>50% residual tumor per tumor bed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (DFS) | From randomization through 5 years follow-up (median follow-up 65.7 months) | Time from randomization to the first occurrence of local recurrence, regional recurrence, distant metastases, or death from any cause. Disease recurrence was assessed using CT imaging with contrast, upper endoscopy for local recurrence, histological confirmation when feasible, and multidisciplinary team review of imaging findings. |
| Overall Survival (OS) | From randomization through 5 years follow-up (median follow-up 65.7 months) | Time from randomization to death from any cause. Patients alive at the time of analysis were censored on the date of the last follow-up visit. Vital status was verified through multiple sources: direct clinical follow-up, telephone contact, cross-referencing with local death registry records, and review of medical records from other healthcare facilities. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FLOT Chemotherpy Regimen A total of four preoperative and four postoperative cycles of FLOT chemotherapy administered
A cycle consists of Day 1 5-FU 2600mg/M2 administered via intravenous PICC for 24 hour Leucovorin 200mg/M2 intravenous Oxaliplatin 85mg/ M2 intravenous Docetaxel 50mg/M2 intravenous
Repeated every 15th day
Three drug Chemotherapy: 5-FU+Leucovorin+Docetaxel+Oxaliplatin | 31 |
| SOX Chemotherapy Regimen Three preoperative cycles and three postoperative cycles of SOX chemotherapy administered
A cycle consists of Day 1: Oxaliplatin 130mg/M2 intravenous Day 1-14 Tegafur gimeracil oteracil (TGO) potassium capsule 80mg/M2 oral (twice daily)
Repeated every 21st day
Two drug Chemotherapy: Oxaliplatin+TGO | 24 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Early surgery (for acute bleeding) | 3 | 0 |
| Overall Study | Protocol Violation | 0 | 3 |
| Overall Study | Refusal to surgery | 4 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | FLOT Chemotherpy Regimen | SOX Chemotherapy Regimen | Total |
|---|---|---|---|
| Age, Customized <=60 | 7 Participants | 14 Participants | 21 Participants |
| Age, Customized 61-70 | 16 Participants | 7 Participants | 23 Participants |
| Age, Customized 71-80 | 8 Participants | 3 Participants | 11 Participants |
| BMI | 23.56 kg/m^2 | 23.49 kg/m^2 | 23.56 kg/m^2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 31 Participants | 24 Participants | 55 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 31 participants | 24 participants | 55 participants |
| Sex: Female, Male Female | 9 Participants | 10 Participants | 19 Participants |
| Sex: Female, Male Male | 22 Participants | 14 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 21 / 40 | 20 / 34 |
| other Total, other adverse events | 9 / 40 | 5 / 34 |
| serious Total, serious adverse events | 9 / 40 | 8 / 34 |
Outcome results
Primary
Total Percentage of Patients With Pathological Complete Tumor Regression (TRG1a) and Sub-total Tumor Regression (TRG1b) in the Primary Tumour
Tumor regression grade (TRG), Becker criteria Grade 1a :Complete tumor regression: 0% residual tumor per tumor bed Grade 1b: Subtotal tumor regression: \<10% residual tumor per tumor bed Grade 2: Partial tumor regression: 10-50% residual tumor per tumor bed Grade 3: Minimal or no tumor regression: \>50% residual tumor per tumor bed
Time frame: Three months
Population: Intention-to-treat (ITT) population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FLOT Chemotherpy Regimen | Total Percentage of Patients With Pathological Complete Tumor Regression (TRG1a) and Sub-total Tumor Regression (TRG1b) in the Primary Tumour | Grade 1b: Subtotal tumor regression | 7 Participants |
| FLOT Chemotherpy Regimen | Total Percentage of Patients With Pathological Complete Tumor Regression (TRG1a) and Sub-total Tumor Regression (TRG1b) in the Primary Tumour | Pathology not available | 9 Participants |
| FLOT Chemotherpy Regimen | Total Percentage of Patients With Pathological Complete Tumor Regression (TRG1a) and Sub-total Tumor Regression (TRG1b) in the Primary Tumour | Grade 2: Partial tumor regression | 13 Participants |
| FLOT Chemotherpy Regimen | Total Percentage of Patients With Pathological Complete Tumor Regression (TRG1a) and Sub-total Tumor Regression (TRG1b) in the Primary Tumour | Grade 3: Minimal or no tumor regression | 10 Participants |
| FLOT Chemotherpy Regimen | Total Percentage of Patients With Pathological Complete Tumor Regression (TRG1a) and Sub-total Tumor Regression (TRG1b) in the Primary Tumour | Grade 1a: Complete tumor regression | 1 Participants |
| SOX Chemotherapy Regimen | Total Percentage of Patients With Pathological Complete Tumor Regression (TRG1a) and Sub-total Tumor Regression (TRG1b) in the Primary Tumour | Grade 3: Minimal or no tumor regression | 6 Participants |
| SOX Chemotherapy Regimen | Total Percentage of Patients With Pathological Complete Tumor Regression (TRG1a) and Sub-total Tumor Regression (TRG1b) in the Primary Tumour | Grade 1a: Complete tumor regression | 0 Participants |
| SOX Chemotherapy Regimen | Total Percentage of Patients With Pathological Complete Tumor Regression (TRG1a) and Sub-total Tumor Regression (TRG1b) in the Primary Tumour | Grade 1b: Subtotal tumor regression | 11 Participants |
| SOX Chemotherapy Regimen | Total Percentage of Patients With Pathological Complete Tumor Regression (TRG1a) and Sub-total Tumor Regression (TRG1b) in the Primary Tumour | Grade 2: Partial tumor regression | 7 Participants |
| SOX Chemotherapy Regimen | Total Percentage of Patients With Pathological Complete Tumor Regression (TRG1a) and Sub-total Tumor Regression (TRG1b) in the Primary Tumour | Pathology not available | 10 Participants |
Secondary
Disease-free Survival (DFS)
Time from randomization to the first occurrence of local recurrence, regional recurrence, distant metastases, or death from any cause. Disease recurrence was assessed using CT imaging with contrast, upper endoscopy for local recurrence, histological confirmation when feasible, and multidisciplinary team review of imaging findings.
Time frame: From randomization through 5 years follow-up (median follow-up 65.7 months)
Population: Intention-to-treat population including all 74 randomized patients regardless of treatment completion or protocol adherence. Complete vital status obtained for all patients with median follow-up of 65.7 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FLOT Chemotherpy Regimen | Disease-free Survival (DFS) | 23.0 months |
| SOX Chemotherapy Regimen | Disease-free Survival (DFS) | 25.5 months |
Comparison: Disease-free survival analysis in intention-to-treat population. DFS defined as time from randomization to first occurrence of local recurrence, regional recurrence, distant metastases, or death from any cause.p-value: 0.84295% CI: [0.597, 1.884]Log Rank
Secondary
Overall Survival (OS)
Time from randomization to death from any cause. Patients alive at the time of analysis were censored on the date of the last follow-up visit. Vital status was verified through multiple sources: direct clinical follow-up, telephone contact, cross-referencing with local death registry records, and review of medical records from other healthcare facilities.
Time frame: From randomization through 5 years follow-up (median follow-up 65.7 months)
Population: Intention-to-treat population including all 74 randomized patients regardless of treatment completion or protocol adherence. Complete vital status obtained for all patients. At data cut-off, 41 deaths occurred: 21 (52.5%) in FLOT group and 20 (58.8%) in SOX group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FLOT Chemotherpy Regimen | Overall Survival (OS) | 61.5 months |
| SOX Chemotherapy Regimen | Overall Survival (OS) | 67.8 months |
Comparison: Primary survival analysis comparing overall survival between neoadjuvant FLOT and SOX regimens in intention-to-treat population.p-value: 0.75995% CI: [0.595, 2.036]Log Rank