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

Primary Purpose

Esophageal Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
fluorouracil
oxaliplatin
conventional surgery
radiation therapy
Sponsored by
Albany Medical College
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Cancer focused on measuring stage I esophageal cancer, stage II esophageal cancer, stage III esophageal cancer, squamous cell carcinoma of the esophagus, adenocarcinoma of the esophagus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Roswell Park Cancer Institute

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
January 28, 2000
Last Updated
March 25, 2013
Sponsor
Albany Medical College
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00004257
Brief Title
Oxaliplatin and Fluorouracil Plus Radiation Therapy in Treating Patients With Primary Esophageal or Stomach Cancer
Official Title
A Phase I Study of Oxaliplatin in Combination With Continuous Infusion 5-Fluorouracil and Radiation in Esophageal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2007
Overall Recruitment Status
Completed
Study Start Date
January 2000 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
January 2004 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Albany Medical College
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Cancer
Keywords
stage I esophageal cancer, stage II esophageal cancer, stage III esophageal cancer, squamous cell carcinoma of the esophagus, adenocarcinoma of the esophagus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
fluorouracil
Intervention Type
Drug
Intervention Name(s)
oxaliplatin
Intervention Type
Procedure
Intervention Name(s)
conventional surgery
Intervention Type
Radiation
Intervention Name(s)
radiation therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lawrence P. Leichman, MD
Organizational Affiliation
Albany Medical College
Official's Role
Study Chair
Facility Information:
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States

12. IPD Sharing Statement

Citations:
Citation
Smith PF, Booker B, Pendyala L, et al.: Pharmacokinetic modeling of oxaliplatin with and without 5-FU and radiation. [Abstract] Proc Am Assoc Cancer Res 42: A-2913, 542, 2001.
Results Reference
background
Citation
Khushalani N, Nava H, Leichman CG, et al.: A phase I study of oxaliplatin in combination with continous infusion 5-fluorouracil and radiation in esophagus cancer. [Abstract] Proc Am Assoc Cancer Res 42: A-3751, 697, 2001.
Results Reference
result
Citation
Pendyala L, Leichman CG, Clark K, et al.: Oxaliplatin, 5-fluorouracil, and radiation in cancer of the esophagus: a pharmacokinetic (PK)/molecular correlates study. [Abstract] Proc Am Assoc Cancer Res 42: A-3347, 623, 2001.
Results Reference
result

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

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