Phase II Studies Of Donepezil And Ginkgo Biloba In Irradiated Brain Tumor

OBJECTIVES:

Primary

• Determine the effect of donepezil or EGb761 on neurocognitive function in patients who underwent radiotherapy for a primary brain tumor or brain metastases at least 6 months before study registration.

Secondary

• Determine the toxicity of these drugs in these patients.
• Determine the quality of life of patients treated with these drugs.
• Quantify the extent of radiation-induced white matter disease and temporal lobe atrophy in patients treated with these drugs.

OUTLINE: This is an open-label, multicenter study.

• Group 1 (closed to accrual 10/09/03): Patients receive oral donepezil once daily for 24 weeks.
• Group 2: Patients receive oral EGb761 three times daily for 24 weeks. In both groups (group 1 closed to accrual 10/09/03), treatment continues in the absence of unacceptable toxicity.

In both groups (group 1 closed to accrual 10/09/03), quality of life and neurocognitive assessment is performed at baseline and at weeks 6 (group 1 only), 12, 24, and 30.

Patients are followed at 6 weeks.

PROJECTED ACCRUAL: A total of 70 patients (35 per treatment group) will be accrued for this study within 9.5 months. (Group 1 closed to accrual 10/09/03)

DISEASE CHARACTERISTICS:

• Diagnosis of primary brain tumor or brain metastases, meeting 1 of the following criteria:

• No radiographic evidence of disease
• Stable disease, defined as no tumor progression within the past 3 months
• Previously treated with 1 course of localized or whole brain radiotherapy of at least 3,000 cGy at least 6 months before study registration

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• At least 30 weeks

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Not pregnant or nursing
• Negative pregnancy test

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No concurrent chemotherapy

Endocrine therapy

• Concurrent steroid therapy allowed if on stable or decreasing dose

Radiotherapy

• See Disease Characteristics
• No concurrent cranial radiotherapy

Surgery

• No concurrent surgery

Other

• More than 3 months since prior donepezil or EGb761
• No concurrent donepezil (group 2 only)
• No concurrent EGb761 (group 1 only) (closed to accrual 10/09/03)
• No concurrent anticoagulants (e.g., aspirin, dipyridamole, heparin, warfarin, or enoxaparin) (group 2 only)
• No concurrent monoamine oxidase inhibitors (e.g., phenelzine or tranylcypromine)
• No other concurrent therapy