Clinical trial NCT00098501: CCI-779 and EKB-569 in Treating Patients With Advanced Solid Tumors
Official title: A Phase 1 Trial of CCI-779 in Combination With EKB-569, an EGFR Inhibitor, in Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-12-08
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
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
timeFrame: Up to 28 days
measure: Number and severity of all adverse events per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0
timeFrame: Up to 30 days after last dose of study treatment
Secondary outcomes:
measure: Best response according to the Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Time from the start of the treatment until disease progression/recurrence, assessed up to 3 years
measure: Time until any treatment related toxicity
timeFrame: Up to 3 years
measure: Time until treatment related grade 3+ toxicity
timeFrame: Up to 3 years
measure: Time until hematologic nadirs (white blood cells [WBC], absolute neutrophil count [ANC], platelets)
timeFrame: Up to 3 years
measure: Time to progression
timeFrame: Up to 3 years
measure: Time to treatment failure
timeFrame: Time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 years
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Charles Erlichman
role: PRINCIPAL_INVESTIGATOR
References: