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

• ClinicalTrials.gov Identifier: NCT00004868
• Recruitment Status: Completed
• First Posted: May 23, 2003
• Last Update Posted: June 27, 2018
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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
• Actual Study Start Date: March 24, 2000
• Actual Primary Completion Date: September 15, 2004
• Actual Study Completion Date: September 15, 2005

Arms and Interventions

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (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

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

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

National Cancer Institute (NCI)

Investigators

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

More Information

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00004868
• Obsolete Identifiers: NCT00006067
• Other Study ID Numbers: NABTC-9902; CDR0000067527 ( Registry Identifier: PDQ (Physician Data Query) ); MSKCC-01045; NCI-00-C-0173
• First Posted: May 23, 2003
• Last Update Posted: June 27, 2018
• Last Verified: June 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:

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