CCI-779 and EKB-569 in Treating Patients With Advanced Solid Tumors

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Drug: temsirolimus

Drug: pelitinib

Study type

Interventional

Funder types

NIH

Identifiers

NCT00098501

NCI-6200

NCI-2012-01459

MAYO-MC027C

U01CA069912 (U.S. NIH Grant/Contract)

MC027C

CDR0000398176

Details and patient eligibility

About

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.

Full 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.

Enrollment

42 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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