Oxaliplatin (NSC-266046) Plus Protracted Infusion 5-Fluorouracil And Radiation For Potentially Curable Esophageal Cancer: A Phase II Trial With Molecular Correlates
fluorouracil
+ oxaliplatin
+ conventional surgery
Digestive System Diseases+6
+ Digestive System Neoplasms
+ Esophageal Diseases
Treatment Study
Summary
Study start date: September 1, 2004
Actual date on which the first participant was enrolled.OBJECTIVES: Primary * Determine the pathologic complete response probability in patients with stage II or III adenocarcinoma of the esophagus or gastroesophageal junction treated with neoadjuvant oxaliplatin, fluorouracil, and radiotherapy followed by definitive surgical resection. Secondary * Determine the frequency and severity of toxic effects associated with this neoadjuvant regimen in these patients. * Determine the overall survival and progression-free survival of patients treated with this regimen. Exploratory Analyses (subject to funding availability) * Correlate, preliminarily, initial messenger ribonucleic acid (mRNA) levels of the genes for thymidylate synthase (TS), γ-glutamyl transpeptidase (γGT), γ-glutamyl cysteine (γ-GCS), DNA excision repair cross-complementing (ERCC-1), and xeroderma pigmentosum (XPA) with response and survival of patients treated with this regimen. * Correlate, preliminarily, the mRNA levels of TS, γGT, γ-GCS, ERCC-1, and XPA before and after treatment with this regimen with survival of these patients. * Correlate, preliminarily, specific genetic polymorphisms of TS and ERCC-1 with tumor response and overall survival of patients treated with this regimen. OUTLINE: This is a multicenter study. * Neoadjuvant chemoradiotherapy: Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and fluorouracil (5-FU) IV continuously on days 8-43. Beginning on day 8, patients also undergo radiotherapy once daily, 5 days a week, for 5 weeks. * Surgery: Patients with stable disease or better undergo surgical resection 4-10 weeks after completion of chemoradiotherapy. * Adjuvant chemotherapy: Beginning 4-10 weeks after surgery, patients receive chemotherapy comprising oxaliplatin IV over 2 hours on days 1, 15, and 29 and 5-FU IV continuously on days 1-36. Treatment continues in the absence of unacceptable toxicity or disease progression. Patients are followed every 3 months for 1 year and then every 6 months for 2 years. PROJECTED ACCRUAL: A total of 45-85 patients will be accrued for this study within 17-21 months.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.98 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
DISEASE CHARACTERISTICS: * Histologically confirmed primary adenocarcinoma of the thoracic esophagus or gastroesophageal junction * No recurrent disease * Primary esophageal tumor at least 20 cm below the incisors (if \< 26 cm below the incisors, a bronchoscopy must be performed and cytology must be negative) * Esophageal disease confined to esophagus and peri-esophageal soft tissue * Gastroesophageal junction disease extending ≤ 2 cm into the gastric cardia * Clinical stage II or III disease by CT scan or MRI * If no esophageal mass is detected by these methods, esophageal endoscopic ultrasound is required to determine stage * Positron-emission tomography scan is required to confirm stage * Measurable or non-measurable disease by x-ray, scanning, or physical examination * No celiac axis nodes ≥ 1.5 cm * Measurable regional lymph nodes ≥ 1.5 cm at stations 2-10=N1 OR subdiaphragmatic lymph nodes at stations 15-19 ≤ 1.5 cm by CT scan or MRI allowed * Palpable supraclavicular lymph nodes must be free of metastatic esophageal cancer by biopsy PATIENT CHARACTERISTICS: Age * Over 18 Performance status * Zubrod 0-2 Life expectancy * Not specified Hematopoietic * Absolute neutrophil count ≥ 1,500/mm\^3 * White blood cell (WBC) count ≥ 3,000/mm\^3 * Hemoglobin ≥ 10.0 g/dL (transfusion allowed) Hepatic * Albumin ≥ 3 g/dL * Bilirubin normal Renal * Creatinine ≤ 1.5 times upper limit of normal Cardiovascular * No myocardial infarction or cerebrovascular event within the past 6 months Pulmonary * No active pneumonia or inflammatory lung infiltrate Other * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * No peripheral neuropathy ≥ grade 2 * Not pregnant or nursing * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior chemotherapy for esophageal cancer Endocrine therapy * Not specified Radiotherapy * No prior radiotherapy for esophageal cancer * No concurrent intensity-modulated radiotherapy Surgery * No prior surgical resection or attempted surgical resection of esophageal cancer
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.One single intervention group is designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalStudy Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 143 locations
Mobile Infirmary Medical Center
Mobile, United StatesOpen Mobile Infirmary Medical Center in Google MapsProvidence Cancer Center
Anchorage, United StatesHighlands Oncology Group - Springdale
Bentonville, United StatesEast Bay Radiation Oncology Center
Castro Valley, United States