CCI-779 in Treating Patients With Malignant Glioma

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Completed

CT.gov ID

NCT00022724

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

75.6

Actual Duration (Months)

4.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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/II trial to study the effectiveness of CCI-779 in treating patients who have malignant glioma.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: temsirolimus	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose of CCI-779 in patients with malignant glioma.
Determine the safety profile of this drug in these patients.
Determine the pharmacokinetics of this drug in these patients.
Determine the efficacy of this drug, in terms of survival and objective response, in these patients.

OUTLINE: This is a dose-escalation study. Patients in phase II are stratified according to use of enzyme-inducing antiepileptic drugs (EIAEDs) (yes vs no) and disease type (glioblastoma multiforme with stable neuro-imaging after radiotherapy vs recurrent malignant glioma). Patients in phase I must be currently receiving EIAEDs.

Phase I: Patients receive CCI-779 IV over 30 minutes once weekly. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of 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.

Phase II: Patients receive CCI-779 as in Phase I. Patients who are candidates for surgical resection of recurrent disease receive CCI-779 IV over 30 minutes 2 hours prior to surgery and then once weekly, as above, once recovered from surgery.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for phase I of this study within 12 months. A total of 87 patients will be accrued for phase II of this study within 12 months.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

49 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Primary Purpose:

Treatment

Official Title:

Phase I/II Trial Of CCI-779 In Patients With Malignant Glioma

Actual Study Start Date :

Aug 27, 2001

Actual Primary Completion Date :

May 4, 2006

Actual Study Completion Date :

Dec 15, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed intracranial malignant glioma
Glioblastoma multiforme
Anaplastic astrocytoma
Anaplastic oligodendroglioma
Anaplastic mixed oligoastrocytoma
Malignant astrocytoma not otherwise specified
Initial diagnosis of low-grade allowed, if subsequently progressed
Recurrent disease must have documented progression by MRI or CT scan
Progressive disease must have failed prior radiotherapy
Recent resection of recurrent or progressive tumor allowed provided all of the following are met:
Recovered from surgery
CT scan or MRI performed no more than 96 hours postoperatively OR at 4-6 weeks postoperatively
Concurrent steroid dosage must be stable
Confirmation of true progressive disease (by PET, thallium scan, MR spectroscopy, or surgical documentation) required after prior interstitial brachytherapy or stereotactic radiosurgery

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Karnofsky 60-100%

Life expectancy:

More than 8 weeks

Hematopoietic:

WBC at least 3,000/mm3
Absolute neutrophil count at least 2,000/mm3
Platelet count at least 120,000/mm3
Hemoglobin at least 10 g/dL (transfusion allowed)

Hepatic:

Bilirubin less than 1.5 times upper limit of normal (ULN)
SGOT less than 1.5 times ULN
Cholesterol less than 350 mg/dL
Triglycerides less than 400 mg/dL

Renal:

Creatinine less than 1.5 mg/dL
Creatinine clearance at least 60 mL/min

Other:

No active infection
No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
No significant medical illness that would preclude study
No disease that would obscure toxicity or dangerously alter drug metabolism
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to CCI-779 or allergy to or inability to receive antihistamines
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 12 weeks after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

At least 1 week since prior interferon

Chemotherapy:

At least 2 weeks since prior vincristine
At least 3 weeks since prior procarbazine
At least 6 weeks since prior nitrosoureas
Phase I:
2 prior chemotherapy regimens allowed
1 prior adjuvant regimen and 1 prior regimen for recurrent or progressive disease OR
2 prior regimens for progressive tumor
Phase II:
No more than 1 prior chemotherapy regimen for recurrent malignant glioma
No prior chemotherapy allowed for stable glioblastoma multiforme

Endocrine therapy:

See Disease Characteristics
At least 1 week since prior tamoxifen

Radiotherapy:

See Disease Characteristics
At least 4 weeks since prior radiotherapy for progressive disease
No more than 1 month since prior radiotherapy for nonprogressive glioblastoma multiforme

Surgery:

See Disease Characteristics

Other:

Recovered from prior therapy
At least 1 week since prior noncytotoxic agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095
2	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94143
3	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland	United States	20892-1182
4	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
5	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
6	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
7	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232
8	M.D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
9	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-6220
10	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792