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A Phase I Trial of Pre-Surgical O6-Benzylguanine in the Treatment of Patients With Malignant Glioma


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

Thank you

Trial Information

A Phase I Trial of Pre-Surgical O6-Benzylguanine in the Treatment of Patients With Malignant Glioma


OBJECTIVES:

- Determine the dose of O6-benzylguanine (O6-BG) that produces total depletion of tumor
O6-alkylguanine-DNA alkyltransferase (AGT) levels in more than 90% of patients with
cerebral anaplastic astrocytoma or glioblastoma multiforme.

- Determine the qualitative and quantitative toxicities of O6-BG in this patient
population.

OUTLINE: This is a dose escalation study.

Part I: The first cohort of 10 patients receives O6-benzylguanine (O6-BG) IV over 1 hour at
dose level 1 beginning 6 hours prior to surgery. If at least 3 of 10 patients in the first
cohort have detectable levels of O6-alkylguanine-DNA alkyltransferase (AGT), then a second
cohort of 10 patients receives O6-BG as above at dose level 2. Dose escalation continues
until at least 8 of 10 patients have undetectable AGT activity. At this point, 4 additional
patients are accrued. If at least 11 of 14 patients at this dose level have undetectable
levels of AGT, then this dose level constitutes the biologic modulatory dose of O6-BG. If
less than 11 of 14 patients have undetectable levels of AGT, then 10 additional patients are
treated at a higher dose. If at any time 3 or more patients at a dose level have detectable
AGT activity, accrual is stopped at that dose level and patients are treated at the next
higher dose level. (Part I closed to accrual effective 7/10/2000)

Part II: An additional cohort of 14 patients receives O6-BG at dose level 5 beginning 18
hours prior to surgery.

PROJECTED ACCRUAL: Part I of this study closed to accrual effective 7/10/2000. A total of 14
patients will be accrued for part II of this study at a rate of 3 patients per month.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Must be undergoing a diagnostic/therapeutic craniotomy for biopsy/resection of
recurrent or newly diagnosed (or presumed) cerebral anaplastic astrocytoma or
glioblastoma multiforme

- Patients undergoing stereotactic biopsy or partial resection are eligible

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- SWOG 0-2 OR

- Karnofsky 60-100%

Hematopoietic:

- WBC at least 3,500/mm3

- Absolute neutrophil count at least 1,800/mm3

- Platelet count at least 125,000/mm3

- Hemoglobin at least 9 g/dL

Hepatic:

- Bilirubin less than 1.5 mg/dL

- SGOT less than 2 times upper limit of normal

Renal:

- Creatinine less than 1.5 mg/dL OR

- Creatinine clearance greater than 70 mL/min

Cardiovascular:

- No cardiovascular illnesses that cannot be adequately controlled with

- appropriate therapy or would increase risk, e.g.:

- Severe cardiac disease such as uncontrolled arrhythmias or conduction

- defects

- Major problems with edema (e.g., residual leg swelling from deep venous

- thrombosis)

- Recent coronary artery disease

- Poorly controlled hypertension (systolic pressure greater than 180 mm Hg,

- diastolic pressure greater than 110 mm Hg)

Other:

- No other medical illnesses that cannot be adequately controlled with

- appropriate therapy or would increase risk, e.g.:

- Major problems with edema (e.g., Cushing's syndrome)

- Major psychiatric illness

- No other malignancy requiring active therapy

- Not pregnant or nursing

- Fertile patients must us effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- Must have failed or received no prior treatment with a nitrosourea,

- procarbazine, or temozolomide

- No prior O6-benzylguanine

- At least 4 weeks since prior chemotherapy and recovered

Endocrine therapy:

- Not specified

Radiotherapy:

- At least 6 weeks since prior radiotherapy

- No prior radiotherapy to greater than 10-20% of bone marrow

Other:

- No concurrent therapy for any other malignancy

- At least 2 weeks since other prior investigational drug

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Michael Prados, MD

Investigator Role:

Study Chair

Investigator Affiliation:

UCSF Medical Center at Parnassus

Authority:

United States: Federal Government

Study ID:

CDR0000065479

NCT ID:

NCT00002971

Start Date:

April 1997

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • recurrent adult brain tumor
  • adult glioblastoma
  • adult anaplastic astrocytoma
  • adult giant cell glioblastoma
  • adult gliosarcoma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms
  • Glioma

Name

Location

University of Texas - MD Anderson Cancer CenterHouston, Texas  77030-4009
University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781
Simmons Cancer Center - DallasDallas, Texas  75235-9154
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
UCSF Cancer Center and Cancer Research InstituteSan Francisco, California  94115-0128
University of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania  15213
University of Wisconsin Comprehensive Cancer CenterMadison, Wisconsin  53792
Dana-Farber Cancer InstituteBoston, Massachusetts  02115