MK0752 and Gemcitabine Hydrochloride in Treating Patients With Stage III and IV Pancreatic Cancer That Cannot Be Removed by Surgery

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed ductal adenocarcinoma of the pancreas
• Stage III and IV, unresectable disease
• Assessable disease by endoscopic ultrasound or CT guidance
• Tissue that is assessed by the Investigator as being accessible to biopsy - for patients recruited to dose escalation phase where three previous patients have not already provided biopsies
• No known brain metastases
• Patients with stable symptoms within the past 4 weeks, on a stable dose of steroids, and able to give informed consent are eligible

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Life expectancy ≥ 12 weeks
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count ≥ 1.5 x 10^9/L
• Platelet count ≥ 100 x 10^9/L
• Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT ≤ 2.5 times ULN (≤ 5 times ULN if due to liver metastases)
• PT ≤ 1.5 times ULN
• Creatinine clearance ≥ 50 mL/min (uncorrected)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use two forms of highly effective contraception (females) 4 weeks prior to, during, and for 6 months after completion of study therapy or 1 form of highly effective contraception (males) during and for 6 months after completion of study therapy
• Written (signed and dated) informed consent and capable of cooperating with treatment and follow-up
• No nonmalignant systemic disease, including active uncontrolled infection, that confers a high medical risk to the patient
• No known serologically positive HIV or hepatitis B or C infection
• No other concurrent malignancies except adequately treated cone-biopsied carcinoma in situ of the uterine cervix, basal or squamous cell carcinoma of the skin, or cancer survivors who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease ≥ 5 years, and are deemed at negligible risk for recurrence
• No concurrent congestive heart failure
• No prior history of cardiac disease (New York Heart Association class III-IV disease), cardiac ischemia, or cardiac arrhythmia
• No other condition that, in the investigator's opinion, would not make the patient a good recommendation for the clinical trial

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior treatments
• Previous chemotherapy for advanced disease is permitted. If gemcitabine treatment was given previously, the patient must have tolerated a dose of at least 800mg/m2. Previous chemotherapy for malignant disease must be complete at least 3 weeks before treatment on this trial (six weeks for mitomycin C)
• No major thoracic or abdominal surgery from which the patient has not yet recovered
• No concurrent participation or planned participation in another interventional clinical study
• Concurrent participation in an observational study allowed
• No concurrent warfarin
• Low molecular weight heparin allowed
• No concurrent radiotherapy (except palliative for bone pain), endocrine therapy, or immunotherapy
• No other concurrent anticancer therapy or investigational drugs