Fluorouracil, Cisplatin, Leucovorin Calcium, and Cetuximab in Treating Patients With Adenocarcinoma of the Stomach or Gastroesophageal Junction

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as fluorouracil, cisplatin, and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving more than one drug (combination chemotherapy) together with cetuximab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these drugs after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying the side effects of giving fluorouracil, cisplatin, and leucovorin calcium together with cetuximab and to see how well they work in treating patients with adenocarcinoma of the stomach or gastroesophageal junction.

Detailed Description
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OBJECTIVES: Primary To evaluate the objective response rate according to RECIST V1.1 criteria in patients with adenocarcinoma of the stomach or gastroesophageal junction treated with neoadjuvant chemotherapy comprising fluorouracil, cisplatin, leucovorin calcium, and cetuximab followed by surgery and adjuvant chemotherapy. To determine the non-toxicity rate in these patients. Secondary To determine the rate of macroscopically and microscopically complete surgical resection (R0). To determine the overall tolerance in patients treated with this regimen. To determine post-operative mortality and morbidity in these patients. To determine the rate of recurrence at 1 and 2 years in these patients. To determine recurrence-free survival at 3 years in these patients. To determine disease-free survival at 3 years in these patients. To determine overall survival at 3 years in these patients. To determine quality of life using EORTC QLC-C30 and STO-22 questionnaires. To determine the correlation between the response rate and the degree of skin toxicity. OUTLINE: This is a multicenter study. Neoadjuvant therapy and surgery: Patients receive leucovorin calcium IV over 2 hours, cisplatin IV, fluorouracil IV continuously over 46 hours, and cetuximab IV over 1-2 hours on day 1. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Within 3-4 weeks after completing neoadjuvant chemotherapy, patients undergo surgery. Adjuvant therapy: Within 4-8 weeks after completing neoadjuvant chemotherapy, patients receive leucovorin calcium, cisplatin, fluorouracil, and cetuximab as in neoadjuvant therapy. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients complete quality-of-life questionnaires (QLC-C30 and STO-22) periodically. Blood and tissue samples are collected periodically for correlative and translational studies. After completing study therapy, patients are followed up every 4 months for 2 years and then every 6 months for 1 year.

Official Title
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Trial Evaluating the Efficacy and Tolerance of Perioperative Chemotherapy With 5FU-Cisplatin-Cetuximab in Adenocarcinomas of the Stomach and Gastroesophageal Junction. Phase II Single Arm, Multicenter.

Conditions
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Adenocarcinoma of the Gastroesophageal Junction, Gastric Cancer

Intervention / Treatment
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* Biological: cetuximab
* Drug: cisplatin
* Drug: fluorouracil
* Drug: leucovorin calcium
* Procedure: adjuvant therapy
* Procedure: neoadjuvant therapy
* Procedure: quality-of-life assessment
* Procedure: therapeutic conventional surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction Stage IB, II, or III disease according to TNM classification OR type I, II, or III disease according to Siewert classification TNM: T1N1-3, T2N0-3, T3N0-3, or T4N0-3 (no T1N0 or M1) Disease considered operable with curative intent No gastric scirrhous carcinoma (linitis plastica) Forms with independent cells are not considered linitis Measurable disease according to RECIST V1.1 No planned esophagectomy without thoracotomy in patients with adenocarcinoma of the gastroesophageal junction type I PATIENT CHARACTERISTICS: WHO performance status 0-2 Polynuclear neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Creatinine clearance > 50 mL/min Bilirubin < 1.5 times normal Serum albumin > 30 g/L Prothrombin time ≥ 80% FEV1 > 1 L in case of thoracotomy Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known cirrhosis No other progressive condition that has not been stabilized including the following: Hepatic failure Renal failure Respiratory failure NYHA class III-IV congestive heart failure Unstable angina Myocardial infarction in the past 6 months Significant arrhythmias in the past 12 months No recent weight loss exceeding 15% No interstitial pneumonia No other malignant tumor within the past 5 years except for basal cell skin carcinoma or cancer in situ of the cervix No psychological, familial, or geographical reasons that will preclude the patient being monitored regularly No persons deprived of liberty or under guardianship (Disability Act) PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior chemotherapy or radiotherapy for gastric cancer No other concurrent anticancer treatment, immunotherapy, or hormone therapy No prior abdominal or thoracic radiotherapy

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: Perioperative CT with 5FU-Cisplatine-Cetuximab<br>6 cycles of intravenous Cetuximab (500mg/m²), Cisplatine (50mg/m²) and LV5FU2s (folinic acid 400mg/m², 5FU bolus 400mg/m², and continuous infusion of 5FU 2400mg/m²) every 2 weeks. Surgery was planned 3-4 weeks after the end of neaodjuvant CT and postoperative CT, with the same regimen, planned for 6-8 weeks after surgery. | Biological: cetuximab<br>* 6 cycles of intravenous Cetuximab (500mg/m²),<br>Drug: cisplatin<br>* Cisplatine (50mg/m²)<br>Drug: fluorouracil<br>* LV5FU2s (folinic acid 400mg/m², 5FU bolus 400mg/m², and continuous infusion of 5FU 2400mg/m²) every 2 weeks<br>Drug: leucovorin calcium<br> <br> Procedure: adjuvant therapy<br> <br> Procedure: neoadjuvant therapy<br> <br> Procedure: quality-of-life assessment<br> <br> Procedure: therapeutic conventional surgery<br>* Surgery was planned 3-4 weeks after the end of neaodjuvant CT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate according to RECIST V1.1 criteria |  | 3 months | 
| Non-toxicity rate |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance |  | From Inclusion | 
| Post-operative mortality and morbidity |  | After Surgery | 
| Rate of recurrence at 1 and 2 years |  | 1 year and 2 years | 
| Recurrence-free survival at 3 years |  | 3 years | 
| Disease-free survival at 3 years |  | 3 years | 
| Overall survival at 3 years |  | 3 years | 
| Quality of life as assessed by QLC-C30 and STO-22 questionnaires |  | From inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the gastroesophageal junction, adenocarcinoma of the stomach, stage IB gastric cancer, stage IIA gastric cancer, stage IIB gastric cancer, stage IIIA gastric cancer, stage IIIB gastric cancer, stage IIIC gastric cancer