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

Esophageal Cancer Clinical Trial

Official title:

A Phase I Study of Oxaliplatin in Combination With Continuous Infusion 5-Fluorouracil and Radiation in Esophageal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004257
• Other study ID #: CDR0000067504
• Secondary ID: ALB-RPCI-DS-99-0
• Status: Completed
• Phase: Phase 1
• First received: January 28, 2000
• Last updated: March 25, 2013
• Start date: January 2000
• Est. completion date: January 2004

Study information

• Verified date: December 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: January 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Drug:
• fluorouracil

• oxaliplatin

Procedure:
• conventional surgery

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (2)

Lead Sponsor	Collaborator
Albany Medical College	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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.