CCI-779 in Treating Patients With Advanced Solid Tumors

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

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.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors; Unspecified Adult Solid Tumor, Protocol Specific; Metastatic Cancer
• Intervention / Treatment: Drug: temsirolimus

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: National Cancer Institute (NCI); Wyeth is now a wholly owned subsidiary of Pfizer; University of Texas
• Investigators: Study Chair: Eric K. Rowinsky, MD, San Antonio Cancer Institute

Study record dates

Study Major Dates

• Study Start: January 1, 2001
• Primary Completion (Actual): June 1, 2002
• Study Completion (Actual): June 1, 2002

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: July 14, 2003
• First Posted (Estimate): July 15, 2003

Study Record Updates

• Last Update Posted (Estimate): August 9, 2012
• Last Update Submitted That Met QC Criteria: August 7, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific; recurrent adult brain tumor; tumors metastatic to brain
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: CDR0000066820; P30CA054174 (U.S. NIH Grant/Contract); UTHSC-9785011303 (Other Identifier: UTHSCSA IRB); SACI-IDD-98-02 (Other Identifier: San Antonio Cancer Institute); W-AR-3066K1-100-US (Other Identifier: Wyeth); NCI-V98-1506 (Other Identifier: NCI)