cci-779 and ekb-569 in treating patients with advanced solid tumors

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Summary: this phase i trial is studying the side effects, best way to give, and best dose of cci-779 and ekb-569 in treating patients with advanced solid tumors. drugs used in chemotherapy, such as cci-779, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. ekb-569 may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. giving cci-779 together with ekb-569 may kill more tumor cells.

objectives: i. determine the maximum tolerated dose of the combination of cci-779 and ekb-569 in patients with advanced solid tumors. ii. determine the toxicity of this regimen in these patients. iii. determine the response rate in patients treated with this regimen. outline: this is a dose-escalation study. patients are assigned to 1 of 3 treatment groups. group i: patients receive oral ekb-569 on days 1-28 and oral cci-779 on days 1-7 and 15-21. cohorts of 3-6 patients receive escalating doses of ekb-569 and cci-779 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. group ii: patients receive oral ekb-569 at the mtd on days 4-28 of course 1 and days 1-28 of all subsequent courses and cci-779 at the mtd on days 1-3 and 15-17. group iii: patients receive ekb-569 at the mtd as in group i and oral cci-779 at the mtd on days 7-9 and 19-21 of course 1 and days 1-3 and 15-17 of all subsequent courses. in all groups, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. projected accrual: a total of 30-42 patients (18-30 for group i, 6 for group ii, and 6 for group iii) will be accrued for this study within 1.35-1.75 years.

Eligibility criteria:
inclusion criteria: * histologically confirmed unresectable solid tumor for which there is no known standard therapy that is potentially curative or capable of extending life expectancy * no cns metastases * performance status - ecog 0-2 * at least 12 weeks * absolute neutrophil count ≥ 1,500/mm\^3 * platelet count ≥ 100,000/mm\^3 * hemoglobin ≥ 10 g/dl * bilirubin normal * ast ≤ 3 times upper limit of normal (uln) (5 times uln if liver involvement) * creatinine ≤ 1.5 times uln * no new york heart association class iii or iv heart disease * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 3 months after study participation * fasting cholesterol \< 350 mg/dl * fasting triglycerides \< 400 mg/dl * no uncontrolled infection * no seizure disorder * more than 4 weeks since prior immunotherapy * more than 4 weeks since prior biologic therapy * no concurrent immunotherapy * no concurrent prophylactic colony-stimulating factor therapy * more than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered * no other concurrent chemotherapy * no concurrent oral contraceptives * more than 4 weeks since prior radiotherapy * no prior radiotherapy to \> 30% of bone marrow * no concurrent radiotherapy * more than 7 days since prior cyp3a4 inducers * no prior mtor-targeting agents * no prior epidermal growth factor receptor-targeting agents * no concurrent antiretroviral therapy that induces or inhibits cyp3a4 for hiv-positive patients * no other concurrent investigational agents * no concurrent warfarin