Oxaliplatin and Fluorouracil Plus Radiation Therapy in Treating Patients With Primary Esophageal or Stomach Cancer - Full Text View

Sponsor:	Albany Medical College
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00004257

Purpose

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.

Condition	Intervention	Phase
Esophageal Cancer	Drug: fluorouracil Drug: oxaliplatin Procedure: conventional surgery Radiation: radiation therapy	Phase I

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders Stomach Cancer

Drug Information available for: Fluorouracil Oxaliplatin

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

January 2000

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004257

Locations

United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001

Sponsors and Collaborators

Albany Medical College

National Cancer Institute (NCI)

Investigators

Study Chair:

Lawrence P. Leichman, MD

Albany Medical College

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

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.

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.

Study ID Numbers:	CDR0000067504, ALB-RPCI-DS-99-08, RPCI-DS-99-08, NCI-T99-0061
Study First Received:	January 28, 2000
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00004257 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage I esophageal cancer
stage II esophageal cancer
stage III esophageal cancer
squamous cell carcinoma of the esophagus
adenocarcinoma of the esophagus

Additional relevant MeSH terms:

Antimetabolites
Digestive System Neoplasms
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Esophageal Neoplasms
Physiological Effects of Drugs
Immunosuppressive Agents

Pharmacologic Actions
Neoplasms
Oxaliplatin
Digestive System Diseases
Neoplasms by Site
Therapeutic Uses
Head and Neck Neoplasms
Fluorouracil
Gastrointestinal Neoplasms
Esophageal Diseases

ClinicalTrials.gov processed this record on November 27, 2009