RATIONALE: Drugs used in chemotherapy, such as VNP40101M, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of VNP40101M in treating young patients who have recurrent, progressive, or refractory primary brain tumors.

Condition	Treatment or Intervention	Phase
childhood brain tumor childhood meningioma	Drug: VNP40101M  Procedure: chemotherapy	Phase I

Further Study Details: 

OBJECTIVES: Primary

• Determine the maximum tolerated dose and dose-limiting toxicity of VNP40101M in pediatric patients with recurrent, progressive, or refractory primary brain tumors.

Secondary

• Determine the pharmacokinetics of this drug and its active metabolite VNP4090CE in these patients.
• Determine the efficacy of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to prior therapy (no radiotherapy or focal radiotherapy only and/or ≤ 2 myelosuppressive chemotherapy or biologic therapy regimens vs craniospinal radiotherapy, high-dose chemotherapy, and/or > 2 myelosuppressive chemotherapy or biologic therapy regimens).

Patients receive VNP40101M IV over 30 minutes on days 1-5. Treatment repeats every 42 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 2-6 patients per stratum receive escalating doses of VNP40101M until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 25% of patients experience dose-limiting toxicity. A total of 12 patients are treated at the MTD.

Patients are followed for 3 months.

PROJECTED ACCRUAL: A total of 4-60 patients (2-30 per stratum) will be accrued for this study within 18 months.

Ages Eligible for Study:  up to  21 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed* primary brain tumor, including benign brain tumors (e.g., low-grade glioma)
• Recurrent or progressive disease OR refractory to standard therapy NOTE: *Patients with intrinsic brain stem or diffuse optic pathway tumors do not require histological confirmation, but must have clinical and/or radiographic evidence of disease progression
• No bone marrow disease

PATIENT CHARACTERISTICS: Age

• 21 and under

Performance status

• Karnofsky 50-100% (for patients > 16 years of age) OR
• Lansky 50-100% (for patients ≤ 16 years of age)

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3*
• Platelet count ≥ 100,000/mm^3*
• Hemoglobin ≥ 8 g/dL* NOTE: *Unsupported

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT and AST ≤ 2.5 times ULN
• No overt hepatic disease

Renal

• BUN < 25 mg/dL
• Creatinine ≤ 1.5 times ULN for age OR
• Glomerular filtration rate > 70 mL/min
• No overt renal disease

Cardiovascular

• Shortening fraction ≥ 30%
• EKG normal
• No overt cardiac disease

Pulmonary

• DLCO ≥ 60% of predicted
• Chest X-ray normal (defined as absence of pulmonary infiltrates, pneumonitis, pleural effusion, pulmonary hemorrahge, or fibrosis) AND a resting pulse oximetry reading of > 94% in room air (for patients who cannot perform the DLCO)
• No overt pulmonary disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Neurologic deficits allowed provided there has been no deficit progression for ≥ 1 week before study entry
• No uncontrolled infection
• No known hypersensitivity to polyethylene glycol

PRIOR CONCURRENT THERAPY: Biologic therapy

• At least 6 months since prior allogeneic bone marrow or stem cell transplantation
• At least 3 months since prior autologous bone marrow or stem cell transplantation
• More than 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa)
• At least 3 weeks since prior myelosuppressive anticancer biologic therapy
• No concurrent routine colony-stimulating factors

Chemotherapy

• At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy

• Concurrent corticosteroids allowed provided dose is stable or decreasing for ≥ 1 week before study entry

Radiotherapy

• At least 3 months since prior craniospinal irradiation ≥ 18 Gy
• At least 2 weeks since prior focal irradiation to the primary tumor and/or symptomatic metastatic sites

Surgery

• Not specified

Other

• At least 7 days since prior nonmyelosuppressive anticancer therapy
• At least 7 days since prior investigational agents
• Concurrent enzyme-inducing anticonvulsant drugs allowed
• No other concurrent anticancer or experimental agents or therapies

California
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94143,  United States; Recruiting
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States; Recruiting
Illinois
      Children's Memorial Hospital - Chicago, Chicago,  Illinois,  60614,  United States; Recruiting
Maryland
      Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support, Bethesda,  Maryland,  20892-1182,  United States; Recruiting
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104-4318,  United States; Recruiting
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States; Recruiting
Tennessee
      St. Jude Children's Research Hospital, Memphis,  Tennessee,  38105-2794,  United States; Recruiting
Texas
      Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital, Houston,  Texas,  77030-2399,  United States; Recruiting
Washington
      Children's Hospital and Regional Medical Center - Seattle, Seattle,  Washington,  98105,  United States; Recruiting

Study chairs or principal investigators

Sri Gururangan, MD,  Study Chair,  Duke Comprehensive Cancer Center   
Christopher Turner, MD,  Dana-Farber/Harvard Cancer Center   

Study ID Numbers:  CDR0000396779; PBTC-017; VION-VNP40101M; NCT00098761
Record last reviewed:  March 2005
Last Updated:  April 5, 2005
Record first received:  December 8, 2004
ClinicalTrials.gov Identifier:  NCT00098761
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08