A Phase I/II Study of Weekly Intravenous Oxaliplatin in Combination With Oral Daily Capecitabine and Radiation Therapy in the Neoadjuvant Treatment of Rectal Cancer
Data Collection
Colonic Diseases+9
+ Digestive System Diseases
+ Digestive System Neoplasms
Treatment Study
Summary
Study start date: September 1, 2003
Actual date on which the first participant was enrolled.OBJECTIVES: Primary * Determine the maximum tolerated dose of neoadjuvant oxaliplatin and capecitabine when combined with radiotherapy in patients with locally advanced adenocarcinoma of the rectum. (Phase I closed to accrual as of 06/2005.) * Determine the rate of complete pathological response in patients treated with this regimen. Secondary * Determine the overall survival of patients treated with this regimen. * Determine the rate of local and overall failure in patients treated with this regimen. * Determine the utility of TS, TP, DPD, ERCC-1, and apoptosis to predict response in patients treated with this regimen. * Determine the rate of pathologic down-staging in patients treated with this regimen. * Determine the safety and toxicity of this regimen in these patients. * Determine the rate of sphincter-saving rectal surgery in patients treated with this regimen who had been deemed candidates for abdominoperineal resection at diagnosis. OUTLINE: This is a multicenter, phase I (phase I closed to accrual as of 06/2005), dose-escalation study of oxaliplatin and capecitabine followed by a phase II study. * Phase I (closed to accrual as of 06/2005): Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks and receive oral capecitabine twice daily on days radiotherapy is administered. Beginning on day 1 of radiotherapy, patients also receive oxaliplatin IV over 2 hours on days 1, 8, 15, 22, and 29. Cohorts of 3-6 patients receive escalating doses of oxaliplatin and capecitabine 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. * Phase II: Patients undergo radiotherapy and receive capecitabine and oxaliplatin as in phase I at the MTD. All patients undergo curative-intent surgery 6-8 weeks after the completion of chemoradiotherapy. Patients are followed every 3 months for 3 years and then every 6 months for 2 years. PROJECTED ACCRUAL: A total of 31-40 patients (6-15 for phase I \[phase I closed to accrual as of 06/2005\] and 25 for phase II) will be accrued for this study within 2 years.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.37 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.From 18 to 75 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 adenocarcinoma of the rectum * Tumor involving the distal 12 cm of the rectum (above the anal verge) * Clinically staged by endoscopic ultrasound with one of the following criteria: * T3-T4 disease * Evidence of lymph node involvement, defined by the presence of ≥ 1 enlarged peri-rectal lymph node (≥ 1 cm in size) * No known distant metastases PATIENT CHARACTERISTICS: Age * 18 to 75 Performance status * ECOG 0-1 OR * Karnofsky 70-100% Life expectancy * More than 1 year Hematopoietic * WBC ≥ 3,000/mm\^3 * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * Bilirubin normal * AST and ALT ≤ 2.5 times upper limit of normal Renal * Creatinine normal OR * Creatinine clearance ≥ 60 mL/min Cardiovascular * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia Other * Able to receive oral medication * No other malignancy within the past 5 years except nonmelanoma skin cancer * No prior or concurrent significant neuropathy * No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drugs * No ongoing or active infection * No other concurrent uncontrolled illness * No psychiatric illness or social situation that would preclude study compliance * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective double-method contraception during and for 3 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent granulocyte-stimulating factors Chemotherapy * No prior chemotherapy Endocrine therapy * Not specified Radiotherapy * No prior pelvic radiotherapy Surgery * Not specified Other * No other concurrent investigational agents * No other concurrent anticancer agents or therapies
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.Study 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 1 location