Completed

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

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What is being tested

O6-benzylguanine

Drug
Who is being recruted

Brain Diseases+15

+ Central Nervous System Diseases

+ Glioma

From 18 to 120 Years
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 1
Interventional
Study Start: June 1997
See protocol details

Summary

Principal SponsorSidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Last updated: June 27, 2018
Sourced from a government-validated database.Claim as a partner

Study start date: June 19, 1997

Actual date on which the first participant was enrolled.

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.

NCT00002971
Principal SponsorSidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Last updated: June 27, 2018
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Treatment Study

These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria

Any sex

Biological sex of participants that are eligible to enroll.

From 18 to 120 Years

Range of ages for which participants are eligible to join.

Healthy volunteers not allowed

If individuals who are healthy and do not have the condition being studied can participate.

Conditions

Pathology

Brain DiseasesCentral Nervous System DiseasesGliomaNeoplasmsNeoplasms by Histologic TypeNeoplasms by SiteNeoplasms, Germ Cell and EmbryonalNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueNervous System DiseasesNervous System NeoplasmsNeuroectodermal TumorsNeoplasms, NeuroepithelialAstrocytomaBrain NeoplasmsGlioblastomaCentral Nervous System NeoplasmsGliosarcoma

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

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.

This study has 9 locations

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, United StatesOpen Jonsson Comprehensive Cancer Center, UCLA in Google Maps

UCSF Cancer Center and Cancer Research Institute

San Francisco, United States

Dana-Farber Cancer Institute

Boston, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, United States
Completed9 Study Centers