Oxaliplatin and Fluorouracil Plus Radiation Therapy in Treating Patients With Primary Esophageal or Stomach Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining more than one drug and combining chemotherapy with radiation therapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining oxaliplatin and fluorouracil plus radiation therapy in treating patients who have primary esophageal or stomach cancer.

Detailed Description
-----------------
OBJECTIVES: Determine the maximum tolerated dose and dose-limiting toxicity of oxaliplatin when given in combination with continuous-infusion fluorouracil and radiotherapy in patients with primary cancer of the thoracic esophagus or gastroesophageal junction. Determine the pharmacokinetics of this regimen in this patient population. Assess somatic p53 mutations in cancer of the esophagus and determine their relation to therapeutic response induced by this regimen. Assess, in a preliminary manner, the efficacy of this regimen in these patients. OUTLINE: This is a dose-escalation study of oxaliplatin and fluorouracil. Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and fluorouracil IV continuously on days 8-42. Patients also undergo radiotherapy once daily, 5 days a week, for 6 weeks beginning on day 8. Patients without evidence of distant disease or unresectable local regional invasion undergo esophageal resection between days 63-70 (within 3-4 weeks after completion of chemoradiotherapy). Patients then receive oxaliplatin as above on days 105, 119, and 133 and fluorouracil as above on days 105-147. Cohorts of 3-6 patients receive escalating doses of oxaliplatin and fluorouracil until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 4 weeks. PROJECTED ACCRUAL: A total of 56 patients will be accrued for this study within approximately 3 years.

Official Title
-----------------
A Phase I Study of Oxaliplatin in Combination With Continuous Infusion 5-Fluorouracil and Radiation in Esophageal Cancer

Conditions
-----------------
Esophageal Cancer

Intervention / Treatment
-----------------
* Drug: fluorouracil
* Drug: oxaliplatin
* Procedure: conventional surgery
* Radiation: radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed primary squamous cell carcinoma or adenocarcinoma of the thoracic esophagus (below 20 cm from incisors) or gastroesophageal (GE) junction Stage I-III Bronchoscopy with biopsy and cytology required if primary esophageal cancer is less than 26 cm from incisors No disease outside esophagus and peri-esophageal soft tissue GE junction tumors must be confined to no greater than 2 cm into the gastric cardia Supraclavicular lymph nodes at station 1 must be less than 1.5 cm or nonpalpable by physical examination Nodes 1.5 cm or greater or palpable by physical examination must be confirmed to be nonmalignant by biopsy Subdiaphragmatic lymph nodes at stations 15-20 must be no greater than 1.5 cm No recurrent disease No known brain metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: WBC at least 3,000/mm3 Granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin normal AST/ALT no greater than 2.5 times upper limit of normal (ULN) Alkaline phosphatase no greater than 2.5 times ULN Renal: Creatinine normal OR Creatinine clearance at least 60 mL/min Cardiovascular: No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No grade 2 peripheral neuropathy No history of allergy to platinum compounds No history of allergy to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy No other concurrent uncontrolled illness No ongoing or active infection No other malignancy within the past 5 years PRIOR CONCURRENT THERAPY: Biologic therapy: No colony-stimulating factor therapy during first study course Chemotherapy: No prior chemotherapy for esophageal cancer At least 4 weeks since other prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy for esophageal cancer At least 4 weeks since other prior radiotherapy Surgery: No prior resection or attempted resection of esophageal cancer Other: No other concurrent investigational drugs No other concurrent commercial agents or therapies for esophageal cancer No concurrent highly active antiretroviral agents (HAART) for HIV-positive patients

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: fluorouracil|nan|
|Drug: oxaliplatin|nan|
|Procedure: conventional surgery|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage I esophageal cancer, stage II esophageal cancer, stage III esophageal cancer, squamous cell carcinoma of the esophagus, adenocarcinoma of the esophagus