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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00004868
First received: March 7, 2000
Last updated: November 22, 2008
Last verified: March 2003
  Purpose

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 Intervention Phase
Brain and Central Nervous System Tumors
Drug: semaxanib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase I/II Trial of SU5416 in Patients With Recurrent High Grade Astrocytomas or Mixed Gliomas

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: February 2000
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: 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
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15213-3489
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
Investigators
Study Chair: Howard A. Fine, MD NCI - Neuro-Oncology Branch
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00004868     History of Changes
Obsolete Identifiers: NCT00006067
Other Study ID Numbers: CDR0000067527, NABTC-9902, MSKCC-01045, NCI-00-C-0173
Study First Received: March 7, 2000
Last Updated: November 22, 2008
Health Authority: United States: Federal Government

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:
Astrocytoma
Glioma
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

ClinicalTrials.gov processed this record on April 14, 2014