gw786034 in treating patients with advanced solid tumors

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Summary: rationale: gw786034 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth and by stopping blood flow to the tumor. purpose: this phase i trial is studying the side effects and best dose of gw786034 in treating patients with advanced solid tumors.

objectives: * determine the safety and tolerability of gw786034 in patients with advanced solid tumors. * determine the maximum tolerated dose of this drug in these patients. * determine the pharmacokinetics of this drug in these patients. * determine the clinical response in patients treated with this drug. * evaluate the effect of this drug on biomarkers of angiogenesis activity in order to estimate activity and to determine the minimum biologically active dose in these patients. outline: this is an open-label, nonrandomized, dose-escalation, multicenter study. patients receive oral gw786034 twice daily. treatment continues in the absence of disease progression or unacceptable toxicity. cohorts of 2-6 patients receive escalating doses of gw786034 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. patients are followed at 21 days. projected accrual: approximately 30-50 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed advanced solid tumor * refractory to standard therapy or for which no standard therapy exists * no untreated leptomeningeal or brain metastases * previously treated brain metastases are allowed if currently asymptomatic and patient is off steroids and antiseizure medications for more than 3 months before study entry patient characteristics: age * 21 and over performance status * karnofsky 70-100% life expectancy * at least 12 weeks hematopoietic * absolute granulocyte count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 * hemoglobin at least 9 g/dl hepatic * bilirubin no greater than 1.5 mg/dl * ast and alt no greater than 2 times upper limit of normal (uln) (5 times uln if tumor involvement) renal * creatinine clearance at least 60 ml/min cardiovascular * no uncontrolled hypertension (systolic blood pressure greater than 160 mm hg or diastolic blood pressure greater than 100 mm hg on 2 consecutive measurements separated by 1 week) * no arterial or venous thrombosis (including cerebrovascular accident) within the past 3 months * no myocardial infarction within the past 3 months * no unstable angina within the past 3 months * no cardiac angiopathy or stenting within the past 3 months * no cardiac pacemaker other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 21 days after study treatment * able to swallow and retain oral medication * good venous access * no prior or concurrent gastrointestinal disease * no prior or concurrent condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs * no known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug * no other unstable, pre-existing major medical condition * no orthopedic pins or rods or other embedded metal that would preclude undergoing an mri * no psychological, familial, sociological, or geographical condition that would preclude study compliance prior concurrent therapy: biologic therapy * more than 4 weeks since prior immunotherapy * concurrent epoetin alfa allowed * no concurrent anticancer biologic therapy chemotherapy * more than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) * no concurrent anticancer cytotoxic chemotherapy endocrine therapy * see disease characteristics * more than 4 weeks since prior hormonal or steroid therapy (other than replacement) * no concurrent anticancer hormonal therapy (except for replacement) * no concurrent dexamethasone or prednisone radiotherapy * more than 4 weeks since prior radiotherapy * no concurrent anticancer radiotherapy surgery * more than 4 weeks since prior major surgery * no concurrent surgery for cancer other * recovered from prior therapy * more than 4 weeks since prior investigational agents * more then 28 days since prior alteration of antihypertensive medications * concurrent bisphosphonates allowed * no other concurrent anticancer therapy * no concurrent antidepressants (e.g., amitriptyline, fluoxetine, or fluvoxamine) * no concurrent oral hypoglycemics (e.g., glipizide, glyburide, rosiglitazone, or tolbutamide) * no concurrent therapeutic anticoagulation (e.g., warfarin at therapeutic doses) * low-dose anticoagulation for prophylaxis allowed * no concurrent cyclosporine * no concurrent grapefruit juice * no concurrent amiodarone, mibefradil, phenobarbital, or pioglitazone * no concurrent hypericum perforatum (st. john's wort) * no concurrent rifabutin or diethyldithiocarbamate * no concurrent gestodene, mifepristone, or modafinil * no concurrent herbal supplements, vitamins, or non-traditional compounds

Keywords: unspecified adult solid tumor, protocol specific