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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00004257
Recruitment Status : Completed
First Posted : April 18, 2003
Last Update Posted : March 26, 2013
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)

January 28, 2000
April 18, 2003
March 26, 2013
January 2000
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Complete list of historical versions of study NCT00004257 on Archive Site
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Oxaliplatin and Fluorouracil Plus Radiation Therapy in Treating Patients With Primary Esophageal or Stomach Cancer
A Phase I Study of Oxaliplatin in Combination With Continuous Infusion 5-Fluorouracil and Radiation in Esophageal Cancer

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.


  • 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.

Phase 1
Primary Purpose: Treatment
Esophageal Cancer
  • Drug: fluorouracil
  • Drug: oxaliplatin
  • Procedure: conventional surgery
  • Radiation: radiation therapy
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  • 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.
  • 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.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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January 2004
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  • 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



  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified


  • WBC at least 3,000/mm3
  • Granulocyte count at least 1,500/mm3
  • Platelet count at least 100,000/mm3


  • Bilirubin normal
  • AST/ALT no greater than 2.5 times upper limit of normal (ULN)
  • Alkaline phosphatase no greater than 2.5 times ULN


  • Creatinine normal OR
  • Creatinine clearance at least 60 mL/min


  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia


  • 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


Biologic therapy:

  • No colony-stimulating factor therapy during first study course


  • No prior chemotherapy for esophageal cancer
  • At least 4 weeks since other prior chemotherapy

Endocrine therapy:

  • Not specified


  • No prior radiotherapy for esophageal cancer
  • At least 4 weeks since other prior radiotherapy


  • No prior resection or attempted resection of esophageal cancer


  • 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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
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Albany Medical College
National Cancer Institute (NCI)
Study Chair: Lawrence P. Leichman, MD Albany Medical College
National Cancer Institute (NCI)
December 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP