A Phase I Study of Oxaliplatin in Combination With Continuous Infusion 5-Fluorouracil and Radiation in Esophageal Cancer
18 Years
N/A
Both
Esophageal Cancer
Trial Information
A Phase I Study of Oxaliplatin in Combination With Continuous Infusion 5-Fluorouracil and Radiation in Esophageal Cancer
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Lawrence P. Leichman, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Albany Medical College
Authority:
United States: Federal Government
Study ID:
CDR0000067504
NCT ID:
NCT00004257
Start Date:
January 2000
Completion Date:
January 2004
Related Keywords:
- Esophageal Cancer
- stage I esophageal cancer
- stage II esophageal cancer
- stage III esophageal cancer
- squamous cell carcinoma of the esophagus
- adenocarcinoma of the esophagus
- Esophageal Diseases
- Esophageal Neoplasms
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
