Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Radiation Therapy in Treating Patients With Glioblastoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	Over 18	NCI	NCI-95-C-0069 NCI-95-C-0069A, NCI-95-C-0069D, NCT00019058

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.

Entry 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

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

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 

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Brian G. Fuller, MD, Protocol chair		Ph: 301-496-5457 Email: bgfuller@box-b.nih.gov

Registry Information
Official Title		A PHASE I STUDY OF COMBINED RADIATION RESPONSE MODIFIERS EMPLOYING HYDROXYUREA AND PENTOXIFYLLINE FOR TREATMENT OF GLIOBLASTOMA
Trial Start Date		1995-04-01
Registered in ClinicalTrials.gov		NCT00019058
Date Submitted to PDQ		1995-04-01
Information Last Verified		2001-12-01

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