RATIONALE: SU5416 may stop the growth of brain cancer cells by stopping blood flow to the tumor. PURPOSE: Phase I trial to study the effectiveness of SU5416 in treating children who have recurrent or progressive brain tumors.

Condition	Treatment or Intervention	Phase
Brain Cancer	Procedure: biological response modifier therapy  Procedure: growth factor antagonist therapy  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Drug: SU5416	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the qualitative and quantitative toxicity of SU5416 in pediatric patients with recurrent or progressive brain tumors. II. Determine the acute and chronic dose-limiting toxicity and cumulative toxicity of this regimen in these patients. III. Determine the maximum tolerated dose and pharmacokinetics of this regimen in this patient population. IV. Determine the effects of hepatic enzyme-inducing drugs, such as anticonvulsant agents, on the pharmacokinetics of this regimen in these patients. V. Determine the efficacy, in a preliminary manner, of this regimen in these patients.

PROTOCOL OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to concurrent use of enzyme-inducing anticonvulsant drugs (yes vs no drugs or modest-induction drugs). Patients receive SU5416 IV over 1 hour twice a week for 6 weeks. Treatment repeats every 6 weeks for 17 courses (approximately 2 years) in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients in each stratum 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. Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 50 patients (25 per stratum) will be accrued for this study.

Ages Eligible for Study:  up to  21 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven malignant recurrent or progressive brain tumor at initial presentation or at time of recurrence or progression for which no standard curative therapy exists; Histologic verification for brainstem gliomas may be waived
• Bone marrow involvement allowed

--Prior/Concurrent Therapy--

• Biologic therapy: More than 6 months since prior bone marrow transplantation; More than 1 week since prior growth factor(s)
• Chemotherapy: At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered
• Endocrine therapy: Concurrent dexamethasone allowed if dose stable for at least 1 week prior to study
• Radiotherapy: More than 3 months since prior craniospinal irradiation greater than 24 Gy; More than 3 months since prior total body irradiation; More than 2 weeks since prior focal irradiation to symptomatic metastatic sites; No prior stereotactic radiosurgery; Concurrent total body irradiation allowed
• Surgery: See Radiotherapy
• Other: No other concurrent anticancer or experimental drug therapy; Concurrent anticonvulsant drugs allowed

--Patient Characteristics--

• Age: 21 and under
• Performance status: Karnofsky 60-100%
• Life expectancy: More than 8 weeks
• Hematopoietic: Absolute neutrophil count greater than 1,000/mm3*; Platelet count greater than 75,000/mm3*; Hemoglobin greater than 9 g/dL (*Transfusion independent)
• Hepatic: Bilirubin normal for age; SGOT and SGPT less than 2.5 times normal for age; PT/PTT no greater than 1.2 times upper limit of normal; Albumin greater than 3 g/dL; No overt hepatic disease
• Renal: Creatinine no greater than 1.5 times normal for age OR Glomerular filtration rate greater than 70 mL/min; No overt renal disease
• Cardiovascular: No deep venous or arterial thrombosis within the past 3 months; No history of myocardial infarction, severe or unstable angina, or severe peripheral vascular disease; No overt cardiac disease; No prior cerebral bleeds
• Pulmonary: No pulmonary embolism within the past 3 months; No overt pulmonary disease
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; No known allergies to paclitaxel or other agent that uses Cremophor EL; No uncontrolled infection; Neurological deficits allowed if stable for at least 1 week prior to study; Greater than 3rd percentile weight for height

California
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94143-0128,  United States
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States
Massachusetts
      Dana-Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
Tennessee
      Saint Jude Children's Research Hospital, Memphis,  Tennessee,  38105-2794,  United States
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States
Washington
      Children's Hospital and Regional Medical Center - Seattle, Seattle,  Washington,  98105,  United States

Study chairs or principal investigators

Mark William Kieran,  Study Chair,  Pediatric Brain Tumor Consortium   

Study ID Numbers:  CDR0000068179; PBTC-002
Record last reviewed:  December 2003
Last Updated:  October 13, 2004
Record first received:  September 11, 2000
ClinicalTrials.gov Identifier:  NCT00006247
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08