EGb761 in Maintaining Mental Clarity in Women Receiving Chemotherapy for Newly Diagnosed Breast Cancer

OBJECTIVES:

- Determine the effectiveness of EGb761 in the prevention of chemotherapy-related
cognitive dysfunction in women with breast cancer.

- Determine the safety and tolerability of this drug when administered during adjuvant
chemotherapy in these patients.

- Assess the onset and trajectory of cognitive loss that may occur during chemotherapy in
these patients.

- Assess the quality of life and cognitive role functioning of patients treated with this
drug.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to type of chemotherapy (doxorubicin/cyclophosphamide vs
doxorubicin/cyclophosphamide with taxane vs other anthracycline-based chemotherapy vs other
non-anthracycline-based chemotherapy), age (18 to 49 vs 50 and over), menopausal status at
start of therapy (premenopausal vs postmenopausal vs unknown for surgical reasons), and
lymph node involvement (0-3 vs 4 or more). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive oral EGb761 twice daily.

- Arm II: Patients receive oral placebo twice daily. Patients in both arms receive
treatment beginning no later than the start of the second course of chemotherapy and
continuing until 1 month after the completion of chemotherapy.

Quality of life and cognitive function are assessed at baseline, monthly during
chemotherapy, and then at 1, 6, 12, 18, and 24 months.

Patients are followed every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 220 patients (110 per treatment arm) will be accrued for this
study within 11 months.

DISEASE CHARACTERISTICS:

- Newly diagnosed breast cancer

- Planned standard doses of adjuvant chemotherapy with or without a taxane

PATIENT CHARACTERISTICS:

Age

- 18 and over

Sex

- Female

Menopausal status

- Any status

Performance status

- Eastern Cooperative Oncology Group (ECOG) 0-1

Life expectancy

- At least 6 months

Hematopoietic

- No bleeding diathesis

Hepatic

- serum glutamate oxaloacetate transaminase (SGOT) no greater than 1.5 times upper
limit of normal (ULN)

- Alkaline phosphatase no greater than 1.5 times ULN

Renal

- Creatinine no greater than 1.5 times ULN

Cardiovascular

- No arterial vascular disease

Other

- Able to complete questionnaires alone or with assistance

- No diabetes

- No dementia

- No diagnosis of a psychiatric disorder within the past 5 years that would preclude
study compliance

- No other significant comorbidity

- No known allergy to ginkgo biloba

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No concurrent stem cell transplantation

Chemotherapy

- No concurrent high-dose chemotherapy

Other

- More than 6 months since prior EGb761

- No concurrent antithrombotic therapy (e.g., daily aspirin or anticoagulants)

- Anticoagulants used for central or peripheral line maintenance (i.e., warfarin 1
mg/day or heparin flushes) allowed

- No concurrent dose-intensive regimens

- No concurrent aspirin or aspirin-like medicines (e.g., indomethacin, ibuprofen, or
some antihistamines or heparin or warfarin [except as used above])

- No concurrent regimen expected to cause thrombocytopenia

- No concurrent trazodone, monoamine oxidase inhibitors, or thiazide diuretics (e.g.,
chlorothiazide, hydrochlorothiazide, indapamide, or metolazone)