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

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Chemotherapy may cause memory loss, attention loss, and other problems that make it difficult for patients to think clearly. EGb761 may help maintain mental clarity in patients undergoing chemotherapy. PURPOSE: Randomized clinical trial to study the effectiveness of EGb761 in preventing loss of mental clarity in women who are receiving chemotherapy for newly diagnosed breast cancer.

Detailed Description
-----------------
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.

Official Title
-----------------
The Use of Ginkgo Biloba For The Prevention Of Chemotherapy-Related Cognitive Dysfunction

Conditions
-----------------
Breast Cancer, Neurotoxicity

Intervention / Treatment
-----------------
* Drug: Ginkgo Biloba
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ginkgo Biloba<br>120 mg per day (60 mg BID) | Drug: Ginkgo Biloba<br>* Patients will take 120 mg per day (60 mg BID)<br>|
| Placebo Comparator: Placebo<br>1 tablet BID | Other: Placebo<br>* Patients will take 1 tablet BID<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Level of Cognitive Dysfunction as Measured by the High Sensitivity Cognitive Screen (HSCS) Overall Score. | The primary analysis involved compiling each subscale score for the HSCS into area under the curve (AUC) scores for the data points from baseline to the 12 month data point. HSCS instrument contains questions regarding Memory (0-39), Language (0-30), Visual-motor (0-10), Spatial (0-8), Attention and Concentration (0-25), Self-Regulation and Planning (0-6) on a varying scales. Total is calculated by summing afore mentioned subscales, values of Total ranged from 0 to 125. Lower scores are better. | Baseline, 12 months after starting Chemotherapy. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Scores for Trail Making Tests A and B (Lower Scores Are Better). | The Trail Making Test is a measure of overall brain dysfunction. Time taken to complete TMT tests was recorded. For this analysis median values of the Trail Making tests are calculated at different time points. | Baseline, 1, 6, 12, 18 and 24 months time points | 
| Secondary Measure of Cognitive Function Using Trail Making Tests (TMT) A and B. | TMT A and B were analyzed by evaluating median changes from baseline to different time points. Lower scores are better. The Trail Making Test will provide additional validity and verification for the assessment of overall cognitive dysfunction. Abbreviations used for category titles in the table below: Baseline (BL), change (chg), month (mth). | Baseline, 1, 6, 12, 18 and 24 months post chemotherapy. | 
| Self-reported Symptoms or Side Effects Using Symptom Experience Diary (SED) | Self-reported symptoms or side effects mean change from baseline to 1st post chemo visit (negative numbers indicate worsening symptoms). A descriptive report of the toxicities experienced by participants will be measured with a Symptom Experience Diary. Participants will complete this questionnaire. This patient diary contains several questions related to potential side effects and side benefits of Ginko Biloba measured on a numeric analogue scale (based on 0-10 scale with 10 being worst toxicity). | Baseline, 1st evaluation of post chemotherapy. | 
| Associations Between Self-reported Cognition and the HSCS. | Pearson correlation coefficients conceptually related objective HSCS and subjective self-reported cognition. For this analysis data from both arms are combined. In the table below, numbers closer to 1 indicate positive correlation; numbers closer to -1 indicate negative correlation. | Baseline, 1, 6, 12, 18 and 24 months time points | 
| Associations Between Self-report Measures of Cognition and the Trail Making Test (TMT) A and B. | Pearson correlation coefficients conceptually related objective TMT A and B and subjective self-report measures of cognition. For this analysis data from both arms are combined. In the table below, numbers closer to 1 indicate positive correlation; numbers closer to -1 indicate negative correlation. | Baseline, 1, 6, 12, 18 and 24 months time points | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
neurotoxicity, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer