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.

Condition	Treatment or Intervention	Phase
recurrent adult brain tumor unspecified adult solid tumor, protocol specific brain metastases	Procedure: chemotherapy  Drug: CCI-779	Phase I

Further Study Details: 

OBJECTIVES: I. 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. II. Determine the safety, tolerability, and MTD in patients with recurrent gliomas or brain metastases (part II) who are receiving anticonvulsant therapy. III. Determine the preliminary pharmacokinetic profile and antitumor activity of CCI-779 in these patients.

PROTOCOL 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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY 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)

Part II:

• Histologically proven recurrent gliomas or brain metastases for which no curative therapy exists
• Receiving anticonvulsants

Parts I and II: Measurable or evaluable disease

--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

--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/mm3
• Platelet count at least 100,000/mm3
• 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)

Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Texas
      San Antonio Cancer Institute, San Antonio,  Texas,  78229-3264,  United States

Study chairs or principal investigators

Eric Keith Rowinsky,  Study Chair,  San Antonio Cancer Institute   

Study ID Numbers:  CDR0000066820; UTHSC-9785011303; NCI-V98-1506; SACI-IDD-98-02; W-AR-3066K1-100-US
Record last reviewed:  July 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003712
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08