17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-dmag) in treating patients with metastatic solid tumors or tumors that cannot be removed by surgery

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Summary: rationale: drugs used in chemotherapy, such as 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-dmag), work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. purpose: this phase i trial is studying the side effects and best dose of 17-dmag in treating patients with metastatic solid tumors or tumors that cannot be removed by surgery.

objectives: primary * determine the maximum tolerated dose, dose-limiting toxicity, and recommended phase ii dose of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-dmag) in patients with unresectable or metastatic solid tumors. * determine the feasibility, safety, and toxicity profile of this drug in these patients. secondary * determine the clinical pharmacokinetic profile of this drug in these patients. * determine tumor response in patients treated with this drug. * determine the biologically effective dose. outline: this is an open-label, non-randomized, dose-escalation, multicenter study. patients receive 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-dmag) iv over 1 hour on days 1, 8, 15, and 22. courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of 17-dmag until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. an additional 10 patients are treated at the mtd. after completion of study treatment, patients are followed for 28 days. projected accrual: approximately 25-35 patients will be accrued for this study within 12-18 months.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed solid tumor * unresectable or metastatic disease * standard curative or palliative measures do not exist or are no longer effective or patient refused such measures * no known brain metastases patient characteristics: age * 18 and over performance status * ecog 0-1 life expectancy * more than 12 weeks hematopoietic * absolute neutrophil count \> 1,500/mm\^3 * platelet count ≥ 100,000/mm\^3 * hemoglobin ≥ 9.0 g/dl hepatic * bilirubin normal * alt and ast ≤ 1.5 times upper limit of normal * no chronic liver disease * hepatitis b or c negative renal * creatinine normal or * creatinine clearance normal cardiovascular * no symptomatic new york heart association class iii-iv cardiac disease * no myocardial infarction within the past year * no active ischemic heart disease within the past year * no poorly controlled angina * no uncontrolled dysrhythmia or dysrhythmias requiring antiarrhythmic drugs * no transient ischemic attack * no stroke * no peripheral vascular disease * no congenital long qt syndrome * no history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row) * qtc \< 450 msec (for men) and 470 msec (for woman) * lvef \> 40% by muga * no left bundle branch block pulmonary * no symptomatic pulmonary disease requiring medication, including any of the following: * dyspnea with or without exertion * paroxysmal nocturnal dyspnea * oxygen requirement * significant pulmonary disease (e.g., chronic obstructive/restrictive pulmonary disease other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception 4 weeks before, during, and for 6 months after completion of study treatment * no known hiv positivity * no other malignancy within the past 5 years except adequately treated cone biopsied carcinoma in situ of the cervix or basal cell or squamous cell skin cancer * no ongoing or active infection * no diabetes mellitus (with evidence of severe peripheral vascular disease or ulcers) * no psychiatric illness or social situation that would preclude study compliance * no other uncontrolled illness prior concurrent therapy: biologic therapy * more than 4 weeks since prior immunotherapy * concurrent epoetin alfa allowed chemotherapy * more than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) * no prior 17-n-allylamino-17-demethoxygeldanamycin (17-aag) endocrine therapy * more than 4 weeks since prior endocrine therapy * concurrent luteinizing hormone-releasing hormone analogues for androgen-insensitive prostate cancer and rising prostate-specific antigen allowed radiotherapy * more than 4 weeks since prior radiotherapy (except for palliative treatment) * no prior irradiation field that potentially included the heart (e.g., mantle) surgery * not specified other * recovered from all prior therapy * concurrent bisphosphonates allowed * at least 5 half-lives since prior and no concurrent medication that prolong qtc * no other concurrent anticancer or investigational agents * no concurrent grapefruit juice

Keywords: unspecified adult solid tumor, protocol specific