Gemcitabine Hydrochloride and Tanespimycin in Treating Patients With Stage IV Pancreatic Cancer

Inclusion Criteria

• •Histologically or cytologically confirmed pancreatic adenocarcinoma
• •* Clinical stage IV disease
• •No known brain metastases
• •ECOG performance status 0-2
• •Life expectancy ≥ 12 weeks
• •Absolute Neutrophil Count (ANC) ≥ 1,500/mm³
• •Platelet count ≥ 100,000/mm³
• •Total bilirubin normal
• •Aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal (ULN)
• •Alkaline phosphatase ≤ 2 times ULN (5 times ULN if liver metastases are present)
• •Creatinine normal
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective contraception
• •Ejection fraction \> 40% by echocardiogram
• •* Patients who received prior anthracyclines must have a normal ejection fraction by echocardiogram
• •Corrected QT interval (QTc) \< 500 msec
• •Pulse oximetry \> 88% on room air at rest and after gentle exercise (according to Group Medicare Guidelines)
• •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to tanespimycin (17-AAG) or gemcitabine hydrochloride
• •No known allergy to eggs
• •No concurrent uncontrolled illness including, but not limited to, any of the following:
• •* Ongoing or active infection
• •* Symptomatic congestive heart failure
• •* Unstable angina pectoris
• •* Cardiac arrhythmia
• •* Psychiatric illness/social situations that would limit compliance with study requirements
• •No active ischemic heart disease within the past 12 months
• •No history of uncontrolled dysrhythmias
• •No congenital long QT syndrome
• •No left bundle branch block
• •No other significant cardiac disease, including any of the following:
• •* New York Heart Association class III or IV heart failure
• •* Myocardial infarction within the past year
• •* Poorly controlled angina
• •* Uncontrolled dysrhythmias
• •* History of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
• •No clinically significant interstitial lung disease
• •No symptomatic pulmonary disease requiring medication, including any of the following:
• •* Dyspnea
• •* Dyspnea on exertion
• •* Paroxysmal nocturnal dyspnea
• •* Significant pulmonary disease requiring oxygen\*, including chronic obstructive/restrictive pulmonary disease
• •No pulmonary or cardiac symptoms ≥ grade 2
• •No history of cardiac or pulmonary toxicity after receiving anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or vincristine)
• •No prior chemotherapy for metastatic disease
• •No prior radiotherapy to the chest
• •No prior radiotherapy that potentially included the heart in the field (e.g.,mantle radiotherapy)
• •More than 3 months since prior adjuvant chemotherapy or chemotherapy for locally advanced disease
• •More than 3 weeks since prior radiotherapy
• •No concurrent medications that prolong or may prolong QTc
• •No concurrent antiarrhythmic drugs
• •No concurrent prophylactic colony-stimulating factors
• •No other concurrent investigational agents
• •No other concurrent anticancer therapy