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

Inclusion 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