gemcitabine plus oxaliplatin in treating patients with refractory locally advanced or metastatic pancreatic cancer

Conditions: Pancreatic Cancer

Summary: 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.

Eligibility criteria:
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

Keywords: stage iii pancreatic cancer recurrent pancreatic cancer duct cell adenocarcinoma of the pancreas stage iv pancreatic cancer