A Phase I(Limited)/Phase II Study of Oxaliplatin (OXAL) and Gemcitabine (GEMZAR) in Patients With Metastatic Pancreatic Carcinoma
A Phase I(Limited)/Phase II Study of Oxaliplatin (OXAL) and Gemcitabine (GEMZAR) in Patients With Metastatic Pancreatic Carcinoma
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 II trial to study the effectiveness of combining gemcitabine and oxaliplatin in treating patients who have refractory locally advanced or metastatic pancreatic cancer.
OBJECTIVES: I. Determine the safety and tolerability of gemcitabine plus oxaliplatin in patients with refractory metastatic or locally advanced pancreatic cancer (phase I portion of the study closed as of 7/5/00). II. Determine the objective tumor response rate to this combination regimen in this patient population.
OUTLINE: This is a dose escalation and efficacy study. Patients receive gemcitabine IV over 30 minutes on days 1 and 8 immediately followed by oxaliplatin IV over 2 hours on day 1. Treatment repeats every 3 weeks. Patients achieving stable disease, partial response, or regressive disease continue with therapy. Patients achieving complete response for two consecutive evaluations receive an additional 2 courses of therapy. Phase I (closed as of 7/5/00): Cohorts of 3-6 patients receive escalating doses of gemcitabine and oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity. Phase II: Patients receive the MTD of gemcitabine and oxaliplatin as in phase I. Patients are followed every 3 months for 1 year, and then every 6 months for 4 years.
PROJECTED ACCRUAL: A total of 32-52 patients (12 patients to phase I (phase I closed as of 7/5/00) and 20-40 to phase II) will be accrued for this study within approximately 11-28 months.
DISEASE CHARACTERISTICS: Histologically confirmed ductal or undifferentiated primary pancreatic cancer for which no standard curative therapy exists Progressive locally advanced disease after combined chemotherapy and radiotherapy OR Not a candidate for combined therapy OR Metastatic disease No islet cell, acinar cell, or cystadenocarcinomas Measurable or evaluable disease No known brain metastases
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Karnofsky 50-100% Life expectancy: Not specified Hematopoietic: WBC at least 3,500/mm3 Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than upper limit of normal (ULN) SGOT no greater than 2.5 times ULN Renal: Creatinine no greater than ULN OR Creatinine clearance at least 60 mL/min Cardiovascular: No symptomatic congestive heart failure No unstable angina No cardiac arrhythmia Other: No other uncontrolled illness No active infection No allergy to platinum compounds, gemcitabine, or antiemetics No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix No evidence of neuropathy except preexisting grade I or II Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior biologic therapy or immunotherapy No concurrent immunotherapy Chemotherapy: No prior chemotherapy for metastatic disease At least 6 months since prior adjuvant chemotherapy, including cisplatin or gemcitabine, for radiosensitization in locally advanced disease No prior cisplatin or gemcitabine for locally advanced disease No other concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to 25% or more of bone marrow No concurrent radiotherapy Surgery: Not specified Other: No other concurrent investigational agents