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

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ClinicalTrials.gov Identifier: NCT00004868

Recruitment Status : Completed

First Posted : May 23, 2003

Last Update Posted : November 25, 2008

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by:

National Cancer Institute (NCI)

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 (Clinical Trial)
Primary Purpose:	Treatment
Official Title:	A Phase I/II Trial of SU5416 in Patients With Recurrent High Grade Astrocytomas or Mixed Gliomas
Study Start Date :	February 2000

Resource links provided by the National Library of Medicine

Genetic and Rare Diseases Information Center resources: Glioma Meningioma Glioblastoma Brain Tumor, Adult Anaplastic Astrocytoma Oligodendroglioma Anaplastic Oligodendroglioma Gliosarcoma Neuroepithelioma

U.S. FDA Resources

Arms and Interventions

Outcome Measures

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00004868

Locations


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

Sponsors and Collaborators

North American Brain Tumor Consortium

National Cancer Institute (NCI)

Investigators


Study Chair:	Howard A. Fine, MD	NCI - Neuro-Oncology Branch

More Information


ClinicalTrials.gov Identifier:	NCT00004868 History of Changes
Obsolete Identifiers:	NCT00006067
Other Study ID Numbers:	CDR0000067527 NABTC-9902 MSKCC-01045 NCI-00-C-0173
First Posted:	May 23, 2003 Key Record Dates
Last Update Posted:	November 25, 2008
Last Verified:	March 2003

Keywords provided by National Cancer Institute (NCI):


recurrent adult brain tumor adult meningioma adult glioblastoma adult anaplastic astrocytoma adult anaplastic oligodendroglioma	adult mixed glioma adult grade III meningioma adult giant cell glioblastoma adult gliosarcoma

Additional relevant MeSH terms:


Glioma Astrocytoma Nervous System Neoplasms Central Nervous System Neoplasms Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms by Site	Nervous System Diseases Semaxinib Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

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