Neoadjuvant POF in the Treatment of Locally Advanced Gastric Cancer

Study Overview
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Brief Summary
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This study is a single center, phase II study, to evaluate the effectiveness and safety of POF(paclitaxel plus oxaliplatin plus 5-fluorouracil plus leucovorin) , in the neoadjuvant therapy for patients with advanced/metastatic gastric cancer.

Official Title
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A Phase II Trial of Neoadjuvant POF in the Treatment of Locally Advanced Gastric Cancer

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: paclitaxel ,oxaliplatin,fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-75 years old; Patients must have histologically or cytologically confirmed resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma without distant metastases. GEJ adenocarcinoma may be classified according to Siewert's classification type I, II, or III Patients may have received no prior chemotherapy. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1; An expected survival of ≥ 3 months; Major organ function has to meet the following criteria; (1) For results of blood routine test: Hemoglobin (HB) ≥ 80g / L, ANC(absolute neutrophil count) ≥ 1.5 × 109 / L, PLT(blood platelet) ≥ 75 × 109 / L, (2) For results of biochemical tests: BLT（total bilirubin） ≤ 1.25 times the upper limit of normal (ULN), ALT(Alanine aminotransferase) and AST(aspartate aminotransferase ) ≤ 2.5 × ·ULN, liver metastases, if any, the ALT and AST≤ 5 × ULN, Serum Cr（creatinine）≤1ULN, Endogenous creatinine clearance rate >50ml/min; The patient has a PT（prothrombintime） (INR international normalized ratio) < or = to 1.5 and an PTT（Partial Thromboplastin Time）< than or = to 3 seconds above the upper limits of normal if the patientia t is not on anticoagulation. ·If a patient is on full-dose anticoagulants, the following criteria should be met for enrollment: The patient must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on stable dose of LMW(Low molecular weight) heparin The patient must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices) Pregnancy test (serum or urine) has to be performed for woman of childbearing age within 7 days before enrolment and the test result must be negative. Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter. Ability to understand informed consent and signing of written informed consent document prior to initiation of protocol therapy. Exclusion Criteria: Subjects with second primary cancer, besides dermatoma, primary cancer of nervous system, non-metastatic prostatic neoplasms. Gastrointestinal bleeding. women of child-bearing age must take a negative result of serum pregnancy test within 7 days prior to enrollment, and willing to use appropriate methods of contraception during the trial and 12 weeks after the last trial drug. For men, who willing to use appropriate methods of contraception during the trial and 12 weeks after the last trial drug. Ongoing corticosteroid drug therapy. With a history of previous severe cardiovascular disease: over grade-two myocardial ischemia or myocardial infarction, congestive hert filure, and myocardial infarction or coagulopathy within 6 months. Having got apoplexy or cardiovascular accident within 6 months. Having got severe peripheral vascular disease in clinics. Subjects who have a history of psychiatric substance abuse and cannot quit or have mental disorders. The researchers concluded that the subjects were not suitable for clinic trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: POF<br>A 3-hour infusion of paclitaxel (135 mg/m2) followed by oxaliplatin (85 mg/m2) and leucovorin (400 mg/m2), administered simultaneously over a 2-hour infusion period. Subsequently, a 46-hour infusion of fluorouracil (2400 mg/m2) was administered using an ambulatory pump, repeating every 14 days for 4 cycles | Drug: paclitaxel ,oxaliplatin,fluorouracil<br>* A 3-hour infusion of paclitaxel (135 mg/m2) followed by oxaliplatin (85 mg/m2) and leucovorin (400 mg/m2), administered simultaneously over a 2-hour infusion period. Subsequently, a 46-hour infusion of fluorouracil (2400 mg/m2) was administered using an ambulatory pump, repeating every 14 days for 4 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete and subtotal regression (TRG1a/b by Becker) | Pathological complete and subtotal regression (TRG1a/b by Becker). TRG1a/b is defined as < 10% residual tumor per tumor bed based on evaluation of the resected esophagogastric specimen in the primary by a pathologist. | after 4 cycles (each cycle is 14 days) + surgery; i.e. after 12 weeks in total |