Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Brief 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.
Detailed description
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.
Interventions
DRUGpelitinib
DRUGtemsirolimus
Given PO
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients | Up to 28 days | — |
| Number and severity of all adverse events per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 | Up to 30 days after last dose of study treatment | Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses. |
Secondary
| Measure | Time frame |
|---|---|
| Time until treatment related grade 3+ toxicity | Up to 3 years |
| Time until hematologic nadirs (white blood cells [WBC], absolute neutrophil count [ANC], platelets) | Up to 3 years |
| Best response according to the Response Evaluation Criteria in Solid Tumors (RECIST) | Time from the start of the treatment until disease progression/recurrence, assessed up to 3 years |
| Time to treatment failure | Time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 years |
| Time to progression | Up to 3 years |
| Time until any treatment related toxicity | Up to 3 years |
Countries
United States
Outcome results
None listed