SU5416 in Treating Patients With Recurrent Astrocytoma or Mixed Glioma That Has Not Responded to Radiation Therapy

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Completed

CT.gov ID

NCT00004868

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

65.7

Actual Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: SU5416 may stop the growth of astrocytoma or glioma by stopping blood flow to the tumor.

PURPOSE: Phase I/II trial to study the effectiveness of SU5416 in treating patients who have recurrent astrocytoma or mixed glioma that has not responded to previous radiation therapy.

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

Detailed Description

OBJECTIVES: Phase I:

Determine the maximum tolerated dose of SU5416 in patients with recurrent malignant glioma who are, as well as those who are not, taking enzyme-inducing antiepileptic drugs.
Determine the toxic effects (safety profile) of this drug in this patient population.
Characterize the pharmacokinetics of this drug in these patients.
Develop exploratory data relative to surrogate endpoints of angiogenic activity in vivo, including functional imaging and in vitro assays of endothelial cell inhibition and serum angiogenic peptides.

Phase II:

Determine the efficacy of SU5416, in terms of 6-month progression-free survival, in patients with recurrent high-grade glioma.
Determine, further, the safety profile of the phase II dose of this drug in this patient population.
Develop exploratory data relative to surrogate endpoints of angiogenic activity in vivo including functional imaging and in vitro assays of endothelial cell inhibition and serum angiogenic peptides.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to concurrent enzyme-inducing antiepileptic drugs (no vs yes).

Patients receive SU5416 IV on days 1 and 4 weekly for 4 weeks. Courses repeat every 4 weeks in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of SU5416 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. Once the MTD has been determined, additional patients are accrued to the phase II portion of the study. These patients receive SU5416 IV, as in the phase I portion, at the appropriate MTD established in phase I.

Patients are followed for survival.

PROJECTED ACCRUAL: At least 30 patients will be accrued for the phase I dose-escalation portion of this study within 10 months. An additional 48 patients (32 with glioblastoma multiforme and 16 with anaplastic glioma) will be accrued for the phase II portion of this study within 6-8 months.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Phase I/II Trial of SU5416 in Patients With Recurrent High Grade Astrocytomas or Mixed Gliomas

Actual Study Start Date :

Mar 24, 2000

Actual Primary Completion Date :

Sep 15, 2004

Actual Study Completion Date :

Sep 15, 2005

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 proven supratentorial malignant primary glioma, including:
Glioblastoma multiforme
Anaplastic astrocytoma
Anaplastic oligodendroglioma
Anaplastic mixed oligoastrocytoma
Malignant astrocytoma not otherwise specified
Benign or malignant meningiomas, including brain and spinal meningiomas
Patients with meningiomas are excluded from phase II portion of study
Must have shown unequivocal evidence of tumor recurrence or progression by CT scan or MRI
Must have failed prior radiotherapy
Must have prestudy contrast MRI or contrast CT scan of brain on stable steroid dose within the past 14 days
Must be on stable (unchanged) dose of steroids for at least 5 days before scans
Phase II:
Must have completed radiotherapy at least 2 months prior to enrollment

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Karnofsky 60-100%

Life expectancy:

More than 8 weeks

Hematopoietic:

WBC at least 2,300/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin at least 8 g/dL (transfusion allowed)

Hepatic:

SGOT less than 2.5 times upper limit of normal
Bilirubin normal
No significant active hepatic disease

Renal:

Creatinine less than 1.5 mg/dL OR
Creatinine clearance at least 60 mL/min
No significant active renal disease

Cardiovascular:

No uncompensated coronary artery disease on ECG or physical examination
No history of myocardial infarction or severe/unstable angina within the past 6 months
No deep venous or arterial thrombosis within the past 3 months

Pulmonary:

No pulmonary embolism within the past 3 months

Other:

Not pregnant or nursing
Fertile patients must use effective contraception during and for 2 months after study
No other serious concurrent illness
No significant active psychiatric disease
No diabetes mellitus with severe peripheral vascular disease
No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
No serious active infection
No other concurrent disease that would obscure toxic effects or dangerously alter drug metabolism

PRIOR CONCURRENT THERAPY:

Biologic therapy:

At least 3 weeks since prior biologic therapy (e.g., interferon) and recovered
No concurrent immunotherapy

Chemotherapy:

Phase I:
No more than 2 prior chemotherapy regimens for recurrent disease
Phase II:
No more than 1 prior chemotherapy regimen for recurrent disease
At least 2 weeks since prior vincristine
At least 6 weeks since prior nitrosoureas
At least 3 weeks since prior procarbazine
Recovered from prior chemotherapy
No concurrent chemotherapy

Endocrine therapy:

See Disease Characteristics
At least 3 weeks since prior endocrine therapy (e.g., tamoxifen) and recovered

Radiotherapy:

See Disease Characteristics
No concurrent radiotherapy

Surgery:

Recovered from prior surgery
Recent prior resection of recurrent or progressive tumor allowed

Other:

No other concurrent investigational agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
2	UCSF Cancer Center and Cancer Research Institute	San Francisco	California	United States	94143-0128
3	Neuro-Oncology Branch	Bethesda	Maryland	United States	20892
4	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
5	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0752
6	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
7	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15213-3489
8	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
9	Simmons Cancer Center - Dallas	Dallas	Texas	United States	75235-9154
10	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030-4009
11	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811
12	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164