mFLOT Chemotherapy as First-line Treatment in GC

Study Overview
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Brief Summary
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A single center phase 1b/2 trail to identified suitable dosage and its efficacy of modified FLOT regime in Chinese gastric cancer patients. This trial is designed to identified recommended phase II dose (RP2D) of modified FLOT in Chinese patients, and to evaluate the efficacy of modified FLOT regime as first-line for advanced or metastatic gastric cancer. This trial is in 2 stages: the first stage will establish the maximum tolerated dose (MTD) and RP2D of docetaxel and oxaliplatin in FLOT regime. In the second stage, the efficacy of modified FLOT will be assessed by response rate.

Detailed Description
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The RP2D of FLOT regime will be established with a standard 3+3 design, starting with the dose of 40mg/m2 docetaxel (dose level 1) and 65mg/m2 oxaliplatin (dose level 1). The plan of dose escalation will be found in following table. Chemotherapy will be administered two-weekly (maximum 12 cycles) until progression of disease, intolerable toxicity or withdraw of patients.

Official Title
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Modified FLOT Chemotherapy as First-line Treatment in Advanced or Metastatic Gastric Cancer

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: docetaxel, oxaliplatin, 5-FU, leucovorin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male/female patients aged from 18 to 75 years. Histologically confirmed gastric adenocarcinoma. Gastric tumors should be treatment naïve unresectable or metastatic disease, or recurrence over 6 months after finish of adjuvant chemotherapy. At least one measurable lesion should be confirmed by imaging examination. ECOG performance status 0 or 1 Adequate bone marrow function: Absolute neutrophil count (ANC) ≥1.5x109/L White blood count ≥3.5x109/L Platelets ≥80x109/L Hemoglobin (Hb) ≥90g/L (can be post-transfusion) Adequate renal function: Creatinine Clearance of >50ml/min Adequate liver function: Serum bilirubin <22 umol/L ALT/AST ≤2.5x ULN, for patient with liver metastasis ALT/AST ≤5x ULN 10. Adequate coagulation profile International Normalised Ratio (INR) < 1.5 Activated Prothrombin Time (APTT) < 1.5xULN 11. Without brain metastasis and peripheral nerve diseases 12. Willingness and ability to comply with the protocol for the duration of the study including scheduled visits, examinations, investigations and treatment plans with informed consent form. Exclusion Criteria: With second primary malignant diseases Any contraindication or known hypersensitivity reaction to any of the study drugs, or components of leucovorin, oxaliplatin, 5-FU or docetaxel With uncontrollable complications Inadequate organ function Pregnancy or of child bearing potential.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: modified FLOT<br>modified FLOT Docetaxel 40mg/m2 ivgtt day 1 over 1 hour Oxaliplatin 65mg/m2 ivgtt day 1 over 2hours Dose escalation will be performed. Leucovorin 200mg/m2 ivgtt day 1 over 2 hours 5-FU 2200mg/m2 civ over 24 hours | Drug: docetaxel, oxaliplatin, 5-FU, leucovorin<br>* This is a single-arm study with all patients receiving mFLOT chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose and recommended phase II dose of modified FLOT regime |  | 36 months | 
| Objective response rate |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 36 months | 
| Progression free survival |  | 36 months | 
| Safety: adverse events as assessed by CTCAE v4.0 |  | 36 months |