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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00046891
• Other study ID #: NCCTG-N00C9
• Secondary ID: NCI-2012-02492NC
• Status: Completed
• Phase: Phase 3
• First received: October 3, 2002
• Last updated: July 1, 2016
• Start date: December 2002
• Est. completion date: April 2015

Study information

• Verified date: July 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 226
• Est. completion date: April 2015
• Est. primary completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Neurotoxicity
• Neurotoxicity Syndromes

Intervention

Drug:
• Ginkgo Biloba
Patients will take 120 mg per day (60 mg BID)

Other:
• Placebo
Patients will take 1 tablet BID

Locations

Country	Name	City	State
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania
United States	McFarland Clinic, PC	Ames	Iowa
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	Northside Hospital Cancer Center	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia
United States	Aurora Presbyterian Hospital	Aurora	Colorado
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	WellStar Cobb Hospital	Austell	Georgia
United States	Ochsner Clinic of Baton Rouge	Baton Rouge	Louisiana
United States	MeritCare Clinic - Bemidji	Bemidji	Minnesota
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Deaconess Billings Clinic - Downtown	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare	Billings	Montana
United States	Boulder Community Hospital	Boulder	Colorado
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Brainerd Medical Center	Brainerd	Minnesota
United States	St. Joseph's Medical Center	Brainerd	Minnesota
United States	St. James Community Hospital	Butte	Montana
United States	Graham Hospital	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa
United States	St. Luke's Hospital	Cedar Rapids	Iowa
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia
United States	CCOP - Colorado Cancer Research Program, Incorporated	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	St. Joseph Hospital	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mercy Capitol Hospital	Des Moines	Iowa
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	CCOP - Duluth	Duluth	Minnesota
United States	Miller-Dwan Medical Center	Duluth	Minnesota
United States	St. Mary's - Duluth Clinic Cancer Center	Duluth	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Swedish Medical Center	Englewood	Colorado
United States	Eureka Community Hospital	Eureka	Illinois
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	MeritCare Medical Group	Fargo	North Dakota
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Fremont Memorial Hospital	Fremont	Ohio
United States	Galesburg Clinic	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado
United States	Great Falls Clinic	Great Falls	Montana
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Hattiesburg Clinic, PA at Forrest General	Hattiesburg	Mississippi
United States	Hematology & Oncology Clinic	Hattiesburg	Mississippi
United States	Mason District Hospital	Havana	Illinois
United States	St. Peter's Hospital	Helena	Montana
United States	Hopedale Medical Complex	Hopedale	Illinois
United States	Terrebonne General Medical Center	Houma	Louisiana
United States	Foote Hospital	Jackson	Michigan
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Kenton Oncology, Incorporated	Kenton	Ohio
United States	Kewanee Hospital	Kewanee	Illinois
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Franciscan Skemp Healthcare	La Crosse	Wisconsin
United States	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Gwinnett Medical Center	Lawrenceville	Georgia
United States	Southwest Medical Center	Liberal	Kansas
United States	Lima Memorial Hospital	Lima	Ohio
United States	Cancer Resource Center - Lincoln	Lincoln	Nebraska
United States	Santa Barbara Hematology Oncology - Lompoc	Lompoc	California
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	McDonough District Hospital	Macomb	Illinois
United States	Immanuel St. Joseph's Clinic	Mankato	Minnesota
United States	Kennestone Cancer Center at Wellstar Kennestone Hospital	Marietta	Georgia
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	St. Luke's Hospital	Maumee	Ohio
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Clinic of Dr. Judy L. Schmidt	Missoula	Montana
United States	Community Medical Center	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Trinity Medical Center - East	Moline	Illinois
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital System	Monroe	Michigan
United States	Chippewa County - Montevideo Hospital	Montevideo	Minnesota
United States	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	Ottumwa Regional Health Center Cancer Center	Ottumwa	Iowa
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	St. Mary-Corwin Regional Medical Center	Pueblo	Colorado
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Southern Regional Medical Center	Riverdale	Georgia
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Seton Cancer Institute - Saginaw	Saginaw	Michigan
United States	Coborn Cancer Center	Saint Cloud	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Firelands Regional Medical Center	Sandusky	Ohio
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	Sansum Medical Clinic	Santa Barbara	California
United States	Santa Barbara Hematology Oncology Medical Group at Cancer Center of Santa Barbara	Santa Barbara	California
United States	Adult and Pediatric Urology, P.L.L.P.	Sartell	Minnesota
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sioux Valley Hospital and University of South Dakota Medical Center	Sioux Falls	South Dakota
United States	Cancer Center of Santa Barbara	Snata Barbara	California
United States	Santa Barbara Hematology Oncology - Solvang	Solvang	California
United States	St. Margaret's Hospital	Spring Valley	Illinois
United States	CentraCare Clinic - River Campus	St. Cloud	Minnesota
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	North Suburban Medical Center	Thornton	Colorado
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	St. John Macomb Hospital	Warren	Michigan
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Medical Oncology and Hematology Associates - West Des Moines	West Des Moines	Iowa
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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	No
Secondary	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.	No
Secondary	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.	No
Secondary	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	No
Secondary	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	No