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Phase I Trial of Temodar Plus O6-Benzylguanine (O6-BG) (NSC 637037) in the Treatment of Patients With Newly Diagnosed (Part 1) or Recurrent/Progressive (Parts 1 and 2) Cerebral Anaplastic Gliomas


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

Thank you

Trial Information

Phase I Trial of Temodar Plus O6-Benzylguanine (O6-BG) (NSC 637037) in the Treatment of Patients With Newly Diagnosed (Part 1) or Recurrent/Progressive (Parts 1 and 2) Cerebral Anaplastic Gliomas


OBJECTIVES:

- Determine the dose of O6-benzylguanine (O6-BG) effective in producing complete
suppression of tumor O6-alkylguanine-DNA alkyltransferase activity in patients with
newly diagnosed (closed to accrual 12/19/2000) or recurrent or progressive cerebral
anaplastic glioma.

- Determine the maximum tolerated dose of temozolomide administered after O6-BG in these
patients.

- Determine the toxicity of this regimen in these patients.

- Determine the anti-tumor response in patients treated with this regimen.

OUTLINE: This is a dose-escalation, multicenter study.

- Part I: Patients receive escalating doses of O6-benzylguanine (O6-BG) IV continuously
for 49 hours until the dose that produces the target depletion of tumor
O6-alkylguanine-DNA alkyltransferase (AGT) is determined. Patients undergo a craniotomy
after completion of the O6-BG infusion. (closed to accrual 12/19/2000)

- Part II: After determination of the O6-BG dose in Part I, patients with recurrent
malignant gliomas receive O6-BG IV continuously for 49 hours beginning on day 1.
Patients also receive oral temozolomide on day 1. Treatment repeats every 28 days in
the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6
patients experiences dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 20-30 patients (with 14 patients participating in Part II)
will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Part I:

- Histologically confirmed, newly diagnosed glioblastoma multiforme or anaplastic
astrocytoma (closed to accrual 12/19/2000)

- Parts I and II:

- Histologically confirmed astrocytic, oligodendroglial, or mixed glial tumor

- Grade III or higher

- Recurrent or progressive after radiotherapy

- Evaluable residual disease by contrast-enhanced MRI or CT scan

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- Karnofsky 60-100%

Life expectancy:

- Not specified

Hematopoietic:

- Granulocyte count at least 1,500/mm3

- Platelet count at least 100,000/mm3

Hepatic:

- SGOT no greater than 2.5 times upper limit of normal

- Bilirubin normal

Renal:

- Creatinine no greater than 1.5 mg/dL OR

- Creatinine clearance greater than 60 mL/min

- BUN no greater than 25 mg/dL

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 2 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 6 weeks since prior biologic therapy and recovered

Chemotherapy:

- At least 2 weeks since prior chemotherapy (including but not limited to topotecan)
and recovered

- Patients in trials with one of the following treatment combinations are allowed
to enroll 6 weeks after receiving carmustine (BCNU):

- BCNU on day 1

- BCNU on day 1 and topotecan on days 1, 8, 15, 22, 29, and 36

- BCNU on day 1 and irinotecan on days 1, 8, 15, and 22

Endocrine therapy:

- Patients on corticosteroids must be on a stable dose for at least 2 weeks before
study

- At least 6 weeks since other prior endocrine therapy and recovered

Radiotherapy:

- See Disease Characteristics

- At least 6 weeks since prior radiotherapy and recovered

Surgery:

- Not specified

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Henry S. Friedman, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Duke Cancer Institute

Authority:

United States: Federal Government

Study ID:

1388

NCT ID:

NCT00006474

Start Date:

March 2001

Completion Date:

August 2004

Related Keywords:

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

Name

Location

Duke Comprehensive Cancer CenterDurham, North Carolina  27710