A Pharmacokinetic Study Evaluating the Safety, Tolerability and Maximally Tolerated Dose of 7-Day Continuous Infusions of L-778,123 in Patients With Recurrent of Refractory Solid Malignancies

Date de début de l'étude : 1 avril 1998

DISEASE CHARACTERISTICS: Histologically proven recurrent or refractory solid tumors including, but not limited to: Pancreatic cancer Bladder cancer Colon cancer Head and neck cancer Lung cancer Measurable disease or a measurable tumor marker (not based solely on cytopathological data) No primary or active metastatic CNS disease (assessed by edema or 2 radiologic imaging techniques at least 4 weeks apart) PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: Greater than 3 months Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Hemoglobin at least 9.0 g/dL Platelet count at least 100,000/mm3 PT or PTT no greater than 1.2 times upper limit of normal (ULN) Hepatic: Bilirubin no greater than 1.5 time ULN ALT or AST no greater than 2 times ULN Alkaline phosphatase no greater than 2 times ULN Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No grade 3 cardiac dysrhythmias No atrial fibrillation No prior myocardial infarction No history of unstable angina No history of congestive heart failure LVEF greater than 50% in patients with prior cumulative anthracycline dose less than 450 mg/m2 of doxorubicin Other: HIV negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective double-barrier contraception for at least 2 weeks before, throughout, and at least 2 weeks after the study Permanent central venous catheter in place No history of illicit drug or alcohol abuse within the past 5 years No emotional or psychiatric disorders No known significant drug allergies or serious adverse experiences with marketed or investigational drugs No allergy to latex Normal serum electrolytes No other serious medical disorders No active infections No history of significant retinal disorder or disease No history of seizure disorders PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior immunologic therapy No concurrent immunologic therapy Chemotherapy: At least 4 weeks since prior chemotherapy At least 6 weeks since prior mitomycin or nitrosoureas No prior high dose chemotherapy with stem cell rescue No other concurrent chemotherapy No prior anthracycline dose exceeding the equivalent of greater than 45O mg/m2 of doxorubicin Endocrine therapy: At least 4 weeks since prior endocrine therapy (including steroids) No concurrent endocrine therapy Radiotherapy: At least 4 weeks since prior radiotherapy No prior radiation to greater than 25% of total bone marrow No concurrent radiotherapy Surgery: At least 4 weeks since prior surgery No concurrent surgery Other: At least 30 days since prior investigational agents No concurrent medications with dysrhythmic potential including, but not limited to: terfenadine, astemizole, cisapride, diphenhydramine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, tricyclic antidepressants, haloperidol, risperidone, and indapamine No concurrent rifampin, phenobarbital, phenytoin, or other inducers of CYP3A No concurrent triazolam, alprazolam, midazolam, or other CYP3A metabolized benzodiazepines No concurrent HMG-CoA reductase inhibitors (except fluvastatin) No concurrent anticoagulant therapy (low dose warfarin therapy to maintain catheter patency allowed)