Clinical trial NCT00003712: CCI-779 in Treating Patients With Advanced Solid Tumors
Official title: A Phase I Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous CCI-779 Given Once Daily for 5 Days Every 2 Weeks to Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Metastatic Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: recurrent adult brain tumor
unspecified adult solid tumor, protocol specific
tumors metastatic to brain
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: University of Texas
name: Wyeth is now a wholly owned subsidiary of Pfizer
First posted: 2003-07-15
Enrollment: 15
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: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of CCI-779 in treating patients who have advanced solid tumors.

Detailed description: OBJECTIVES:

* Determine the safety, tolerability, and maximum tolerated dose (MTD) of CCI-779 in patients with advanced solid tumors (part I) who are not receiving anticonvulsant therapy.
* Determine the safety, tolerability, and MTD in patients with recurrent gliomas or brain metastases (part II) who are receiving anticonvulsant therapy.
* Determine the preliminary pharmacokinetic profile and antitumor activity of CCI-779 in these patients.

OUTLINE: This is an open-label, dose-escalation study.

* Part I: Patients receive CCI-779 IV over 30 minutes on days 1-5, followed by a 9 day rest period. Treatment courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

The maximum tolerated dose for part I is defined as the dose level at which 33% of patients experience dose limiting toxicity.

* Part II: Patients receive the same treatment schedule as part I. Three patients with CNS tumors are entered at the dose of CCI-779 determined to be the MTD in Part I. At least 3 patients are entered at each dose level in part II.

PROJECTED ACCRUAL: Approximately 20 patients will be accrued for part I for this study within 8 months, and 12 patients will be accrued for part II within 7 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

Part I:

* Histologically proven advanced solid tumors that are refractory or for which no curative therapy exists
* No CNS metastases, peritumoral edema, or symptomatic brain metastases (part I)
* Measurable or evaluable disease

Part II:

* Histologically proven recurrent gliomas or brain metastases for which no curative therapy exists
* Receiving anticonvulsants
* Measurable or evaluable disease

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2

Life expectancy:

* At least 3 months

Hematopoietic:

* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin at least 9 g/dL

Hepatic:

* Bilirubin less than 1.5 mg/dL
* AST or ALT less than 3 times upper limit of normal (ULN) (less than 5 times ULN if liver metastases)

Renal:

* Creatinine less than 2 mg/dL

Cardiovascular:

* No unstable angina
* No myocardial infarction within past 6 months
* No maintenance therapy for life-threatening arrhythmias

Other:

* Not pregnant or nursing
* Fertile patients must use effective contraception
* HIV negative
* No active infection or other serious concurrent illness
* Triglycerides no greater than 300 mg/dL
* Cholesterol no greater than 350 mg/dL
* No known hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, or azithromycin)

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* At least 3 weeks since prior chemotherapy (6 weeks since nitrosoureas and mitomycin)
* No other concurrent chemotherapy

Endocrine therapy:

* Concurrent corticosteroids used to reduce edema in patients with primary or metastatic CNS tumors allowed
* No concurrent hormonal therapy

Radiotherapy:

* At least 3 weeks since prior radiotherapy
* No concurrent radiotherapy

Surgery:

* Not specified

Other:

* At least 1 month since prior investigational agents
* At least 3 weeks since prior immunosuppressive therapy
* No concurrent anticonvulsant therapy (part I)
* No concurrent immunosuppressive therapy (e.g., terfenadine, cisapride, astemizole, pimozide)
* No known agents that inhibit or induce cytochrome p450

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: San Antonio
country: United States
facility: San Antonio Cancer Institute
state: Texas
Study officials:
affiliation: San Antonio Cancer Institute
name: Eric K. Rowinsky, MD
role: STUDY_CHAIR
References: