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

NCT ID: NCT00004257

Last Updated: 2013-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-01-31
• Study Completion Date: 2004-01-31

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.

Conditions

Esophageal Cancer

Study Design

• Primary Study Purpose: TREATMENT

Interventions

fluorouracil

Intervention Type: DRUG

oxaliplatin

Intervention Type: DRUG

conventional surgery

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Albany Medical College

OTHER

Sponsor Role: lead

Principal Investigators

Lawrence P. Leichman, MD

Role: STUDY_CHAIR

Albany Medical College

Locations

Roswell Park Cancer Institute

Buffalo, New York, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

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.

Reference Type: RESULT

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.

Reference Type: RESULT

Other Identifiers

ALB-RPCI-DS-99-08

Identifier Type: -

Identifier Source: secondary_id

RPCI-DS-99-08

Identifier Type: -

Identifier Source: secondary_id

NCI-T99-0061

Identifier Type: -

Identifier Source: secondary_id

CDR0000067504

Identifier Type: -

Identifier Source: org_study_id