combination chemotherapy in treating patients with metastatic or unresectable solid tumors

Conditions: Recurrent Prostate Cancer; Stage IV Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Summary: this phase i trial is studying the side effects and best dose of combination chemotherapy in treating patients with metastatic or unresectable solid tumors. drugs used in chemotherapy, such as docetaxel and 17-n-allylamino-17-demethoxygeldanamycin, work in different ways to stop tumor cells from dividing so they stop growing or die. combining more than one drug may kill more tumor cells.

objectives: i. determine the maximum tolerated dose of 17-n-allylamino-17-demethoxygeldanamycin (17-aag) administered with docetaxel in patients with progressive metastatic prostate cancer or other progressive metastatic or unresectable solid tumors. ii. determine the pharmacokinetics of this regimen in these patients. outline: this is a dose-escalation study of 17-n-allylamino-17-demethoxygeldanamycin (17-aag). patients are assigned to 1 of 2 treatment groups. group 1: patients receive docetaxel iv over 1 hour and 17-aag iv over 1-2 hours on day 1. courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. group 2: patients receive docetaxel iv over 30 minutes and 17-aag as in group 1. courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients per group receive escalating doses of 17-aag 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. up to 20 additional patients (10 per group) are treated at the mtd. patients are followed every 2-3 months.

Eligibility criteria:
inclusion criteria: * histologically confirmed metastatic or unresectable malignancy for which standard curative or palliative therapy does not exist or is no longer effective * progressive disease manifested by the following parameters * for prostate cancer: * must have castrate, metastatic disease defined by disease progression after surgical castration or treatment with a gonadotropin-releasing hormone (gnrh) analog (testosterone level less than 50 ng/ml) * patients who have not undergone surgical orchiectomy should continue on medical therapies to maintain castrate levels of testosterone * progressive metastatic disease on imaging studies (bone scan, ct scan, or mri) or metastatic disease and a rising prostate-specific antigen (psa) * biochemical progression indicated by at least 3 rising psa values (obtained at least 1 week apart) from a baseline or 2 rising psa values (more than 1 month apart), where the percentage increase over the range of values is at least 25% * patients who have received an antiandrogen as part of first-line hormonal therapy must have shown progression of disease off of the antiandrogen prior to study enrollment * for other solid tumors: * development of new lesions or an increase in pre-existing lesions by bone scintigraphy, ct scan, mri, positron emission tomography, or physical examination * patients whose sole criterion for progression is an increase in a biochemical marker (e.g., carcinoembryonic antigen or ca 15-3) or an increase in symptoms are not eligible * patients with metastatic disease must not be progressing to the extent as to require palliative treatment within 4 weeks of study entry * no active brain metastases * performance status - karnofsky 70-100% * more than 6 months * wbc at least 3,000/mm\^3 * absolute neutrophil count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 * bilirubin ≤ 1.5 times upper limit of normal (uln) * ast and alt \< 1.5 times uln * pt ≤ 1.1 times uln * creatinine no greater than 1.4 mg/dl or within uln * creatinine clearance greater than 55 ml/min * no prior history of pulmonary toxicity after receiving anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine) * no dyspnea ≥ grade 2 at rest on room air * no requirement for supplementary oxygen therapy or oxygen saturations ≤ 88% * no clinically significant pulmonary comorbidities that require medication (e.g., severe chronic obstructive pulmonary disease that could predispose patient to pulmonary toxicity) * qtc ≤ 450 msec for male patients (470 for female patients) * lvef \> 40% by echocardiogram or muga * echocardiogram or muga required for patients with any of the following: * myocardial infarction \> 1 year ago * nyha class i or ii chf * atrial fibrillation * right or left bundle branch block by ekg * no history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row) * no myocardial infarction within the past year * no active ischemic heart disease within the past year * no new york heart association (nyha) class iii or iv congestive heart failure (chf) * no poorly controlled angina * no uncontrolled dysrhythmia * no congenital long qt syndrome * no left bundle branch block * no other significant cardiac disease * no prior history of cardiac toxicity after receiving anthracyclines such as doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no history of severe hypersensitivity reaction to paclitaxel, docetaxel, or polysorbate 80 * no ongoing or active infection * no psychiatric illness or social situation that would preclude study compliance * no grade 2 or greater symptomatic peripheral neuropathy * no allergy to eggs or egg products * no other concurrent uncontrolled illness * at least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) * see disease characteristics * at least 4 weeks since prior radiotherapy and recovered * no concurrent radiotherapy to sole measurable lesion * no prior mantle-field radiotherapy * see disease characteristics * no concurrent surgery for sole measurable lesion * recovered from prior therapy * at least 1 week since prior ketoconazole and recovered * at least 4 weeks since prior investigational anticancer therapeutic drugs * no concurrent combination antiretroviral therapy for hiv-positive patients * no concurrent medications that prolong qtc interval * no concurrent medication used to control arrhythmias * calcium blockers and beta blockers allowed * no other concurrent investigational agents * no other concurrent anticancer agents or therapies (investigational or commercial) * no concurrent cyp3a4 inhibitors, including any of the following: * fluconazole * itraconazole * ketoconazole * macrolide antibiotics (azithromycin, clarithromycin, erythromycin, or troleandomycin) * nifedipine * verapamil * diltiazem * cyclosporine * grapefruit juice * no concurrent cyp3a4 inducers, including any of the following: * carbamazepine * phenobarbital * phenytoin * rifampin * no concurrent herbal extracts or tinctures with cyp3a4 inhibitory activity, including any of the following: * hydrastis canadensis (goldenseal) * hypericum perforatum (st. john's wort) * uncaria tomentosa (cat's claw) * echinacea angustifolia roots * trifolium pratense (wild cherry) * matricaria chamomilla (chamomile) * glycyrrhiza glabra (licorice) * dillapiol * hypericin * naringenin * concurrent cyp3a4 substrates allowed