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A PHASE I STUDY OF COMBINED RADIATION RESPONSE MODIFIERS EMPLOYING HYDROXYUREA AND PENTOXIFYLLINE FOR TREATMENT OF GLIOBLASTOMA


Phase 1
18 Years
N/A
Not Enrolling
Both
Brain and Central Nervous System Tumors

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Trial Information

A PHASE I STUDY OF COMBINED RADIATION RESPONSE MODIFIERS EMPLOYING HYDROXYUREA AND PENTOXIFYLLINE FOR TREATMENT OF GLIOBLASTOMA


OBJECTIVES: I. Determine the maximum tolerated dose of pentoxifylline administered with
hydroxyurea during a course of cranial radiotherapy in patients with glioblastoma
multiforme. II. Determine the toxicity of this regimen in these patients. III. Measure PTX
levels in plasma and CSF in order to assess whether therapeutic drug exposures (e.g.,
0.4-2.0 mM/24 hours) can be achieved with an acceptable level of toxicity. IV. Assess the
local control of glioblastoma in patients treated with this regimen. V. Determine the
response of surrounding normal brain in patients treated with this regimen. VI. Determine
the survival of patients treated with this regimen.

OUTLINE: This is a dose escalation study of pentoxifylline (PTX). Patients receive
hydroxyurea (HU) and PTX IV continuously 5 days a week concurrently with cranial
radiotherapy twice daily, 5 days a week, for 4 weeks in the absence of disease progression
or unacceptable toxicity. The first cohort of 3 patients is treated with radiotherapy and HU
alone. Subsequent cohorts of 3-6 patients receive HU and radiotherapy plus escalating doses
of PTX until the maximum tolerated dose of PTX is determined or serum or CSF drug
concentrations reach 0.4-2.0 mM in 6 consecutive patients with acceptable toxicity. The MTD
is defined as the dose immediately preceding that at which 2 of 6 patients experience
dose-limiting toxicity. Patients are followed at 1 week, at 1 and 3 months, every 3 months
for 2 years, and then every 4 months for 5 years.

PROJECTED ACCRUAL: A maximum of 24-34 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically proven grade IV astrocytoma or glioblastoma
multiforme confined to 1 or both hemispheres of the brain Confirmation of histology by NIH
neuropathology review required MRI or CT completed within 3 weeks of initial evaluation No
clinically apparent leptomeningeal metastases No uncontrolled seizures despite standard
anticonvulsant therapy No history of epilepsy diagnosed a year or more before glioblastoma

PATIENT CHARACTERISTICS: Age: Over 18 Performance status: Karnofsky 80-100% OR ECOG 0-1
Life expectancy: More than 3 months Hematopoietic: WBC at least 3,500/mm3 Absolute
granulocyte count at least 900/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least
10 g/dL No hematologic disease requiring treatment Hepatic: Liver function tests no
greater than 2.5 times upper limit of normal No hepatic disease requiring treatment Renal:
Creatinine no greater than 1.3 mg/dL OR Creatinine clearance at least 95 mL/min No renal
disease requiring treatment Cardiovascular: No history of hospitalization or medication
for: Cardiovascular disease with LVEF 45% or less Myocardial infarction Arrhythmia
Coronary artery disease Angina Congestive heart failure Stroke No thromboembolic disease
requiring treatment Pulmonary: No history of hospitalization or medication for chronic
obstructive pulmonary disease or asthma Other: No peptic ulcer disease or inflammatory
bowel disease within the past 2 years No documented history of intolerance to
methylxanthines (e.g., allergic or serious adverse reactions) No history of psychiatric or
medical illness that would preclude therapy No other malignancy within the past 5 years
except basal cell skin cancer or carcinoma in situ of the cervix No contraindication to
serial CT or MRI (e.g., logistical problems, noncompliance, contrast allergies) Not
pregnant or nursing Negative pregnancy test

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior
chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy Surgery:
Prior biopsy or subtotal or near-total resection allowed At least 7-10 days but no more
than 3 months since prior surgery and/or biopsy Other: No recent methylxanthine-containing
medications No concurrent anticoagulants or methylxanthines (e.g., aspirin, nonsteroidal
antiinflammatory drugs, warfarin, heparin, theophylline, aminophylline, theobromine) for
preexisting medical conditions

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Brian G. Fuller, MD

Investigator Role:

Study Chair

Investigator Affiliation:

NCI - Radiation Oncology Branch; ROB

Authority:

United States: Federal Government

Study ID:

CDR0000064077

NCT ID:

NCT00019058

Start Date:

April 1995

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • adult glioblastoma
  • adult giant cell glioblastoma
  • adult gliosarcoma
  • Glioblastoma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms

Name

Location

Radiation Oncology BranchBethesda, Maryland  20892