RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of oxaliplatin plus irinotecan in treating patients with previously treated metastatic gastrointestinal cancer that has not responded to previous treatment.

Condition	Treatment or Intervention	Phase
Pancreatic Cancer Colon Cancer Gastric Cancer Rectal Cancer Esophageal Cancer Colorectal Cancer adult primary liver cancer	Drug: irinotecan  Drug: oxaliplatin	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose (MTD) for the combination chemotherapy regimen of oxaliplatin plus irinotecan when both drugs are given once a week for four weeks, followed by a two week rest, in patients with metastatic gastrointestinal cancer. II. Evaluate the toxicities of this combination chemotherapy when administered in this manner. III. Determine the pharmacokinetics of platinum and irinotecan at the MTD for this combination chemotherapy in this patient population.

PROTOCOL OUTLINE: This is a dose escalation study. Patients receive oxaliplatin IV over 120 minutes, immediately followed by irinotecan IV over 30 minutes, weekly for 4 weeks (days 1, 8, 15, and 22). Courses are repeated every 42 days. Treatment continues in the absence of unacceptable side effects or disease progression. Sequential dose escalation of oxaliplatin is followed by sequential dose escalation of irinotecan. Dose escalation in cohorts of 3-6 patients each continues 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 toxic effects. Patients are followed approximately every 2-3 months.

PROJECTED ACCRUAL: A total of 2-36 patients will be accrued for this study within 18-36 months.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed metastatic gastrointestinal carcinoma
• Measurable disease
• No CNS metastases
• No obstruction or partial obstruction of GI tract
• No obstruction of genitourinary tract

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior cisplatin, oxaliplatin, nitrosoureas, or mitomycin C 1 or 2 prior chemotherapy regimens allowed (including irinotecan)
• Endocrine therapy: Not specified
• Radiotherapy: No prior radiation therapy to whole pelvis, 30% or greater of bone marrow, and site of measurable disease; At least 4 weeks since prior radiation therapy and recovered
• Surgery: Not specified

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 70-100%
• Life expectancy: Not specified
• Hematopoietic: WBC at least 3,500/mm3; Neutrophil count at least 1,500/mm3; Platelet count at least 125,000/mm3
• Hepatic: Bilirubin less than 1.5 mg/dL
• Renal: Creatinine no greater than 1.5 mg/dL
• Cardiovascular: No uncontrolled high blood pressure, unstable angina, active congestive heart failure, myocardial infarction within prior 6 months, or serious uncontrolled cardiac arrhythmia
• Neurological: No concurrent symptomatic peripheral sensory neuropathy
• Other: No active or uncontrolled infection; Not pregnant or nursing; Fertile patients must use effective contraception

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States

Study chairs or principal investigators

Nancy E. Kemeny,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000066452; MSKCC-98034; NCI-G98-1450
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003427
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08