A Phase 1 Trial of CCI-779 in Combination With EKB-569, an EGFR Inhibitor, in Patients With Solid Tumors
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase 1 Trial of CCI-779 in Combination With EKB-569, an EGFR Inhibitor, in Patients With Solid Tumors
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
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
Outcome Time Frame:
Up to 28 days
Safety Issue:
Yes
Principal Investigator
Charles Erlichman
Investigator Role:
Principal Investigator
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-01459
NCT ID:
NCT00098501
Start Date:
October 2004
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- Neoplasms
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
