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

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

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.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Drug: semaxanib

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 Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 24, 2000
• Primary Completion (ACTUAL): September 15, 2004
• Study Completion (ACTUAL): September 15, 2005

Study Registration Dates

• First Submitted: March 7, 2000
• First Submitted That Met QC Criteria: May 22, 2003
• First Posted (ESTIMATE): May 23, 2003

Study Record Updates

• Last Update Posted (ACTUAL): June 27, 2018
• Last Update Submitted That Met QC Criteria: June 25, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; recurrent adult brain tumor; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; adult meningioma; adult grade III meningioma; adult mixed glioma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms; Astrocytoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Semaxinib
• Other Study ID Numbers: NABTC-9902; CDR0000067527 (REGISTRY: PDQ (Physician Data Query)); MSKCC-01045; NCI-00-C-0173

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No