Clinical trial NCT00046891: EGb761 in Maintaining Mental Clarity in Women Receiving Chemotherapy for Newly Diagnosed Breast Cancer
Official title: The Use of Ginkgo Biloba For The Prevention Of Chemotherapy-Related Cognitive Dysfunction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Neurotoxicity
Keywords: neurotoxicity
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 226
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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)

Primary outcomes:
measure: The Level of Cognitive Dysfunction as Measured by the High Sensitivity Cognitive Screen (HSCS) Overall Score.
timeFrame: Baseline, 12 months after starting Chemotherapy.
Secondary outcomes:
measure: Median Scores for Trail Making Tests A and B (Lower Scores Are Better).
timeFrame: Baseline, 1, 6, 12, 18 and 24 months time points
measure: Secondary Measure of Cognitive Function Using Trail Making Tests (TMT) A and B.
timeFrame: Baseline, 1, 6, 12, 18 and 24 months post chemotherapy.
measure: Self-reported Symptoms or Side Effects Using Symptom Experience Diary (SED)
timeFrame: Baseline, 1st evaluation of post chemotherapy.
measure: Associations Between Self-reported Cognition and the HSCS.
timeFrame: Baseline, 1, 6, 12, 18 and 24 months time points
measure: Associations Between Self-report Measures of Cognition and the Trail Making Test (TMT) A and B.
timeFrame: Baseline, 1, 6, 12, 18 and 24 months time points
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Lompoc
country: United States
facility: Santa Barbara Hematology Oncology - Lompoc
state: California
city: Santa Barbara
country: United States
facility: Sansum Medical Clinic
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Hematology Oncology Medical Group at Cancer Center of Santa Barbara
state: California
city: Snata Barbara
country: United States
facility: Cancer Center of Santa Barbara
state: California
city: Solvang
country: United States
facility: Santa Barbara Hematology Oncology - Solvang
state: California
city: Aurora
country: United States
facility: Aurora Presbyterian Hospital
state: Colorado
city: Boulder
country: United States
facility: Boulder Community Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose Cancer Center at Penrose Hospital
state: Colorado
city: Denver
country: United States
facility: Porter Adventist Hospital
state: Colorado
city: Denver
country: United States
facility: Presbyterian - St. Luke's Medical Center
state: Colorado
city: Denver
country: United States
facility: St. Joseph Hospital
state: Colorado
city: Denver
country: United States
facility: Rose Medical Center
state: Colorado
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program, Incorporated
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Grand Junction
country: United States
facility: St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
state: Colorado
city: Lone Tree
country: United States
facility: Sky Ridge Medical Center
state: Colorado
city: Longmont
country: United States
facility: Hope Cancer Care Center at Longmont United Hospital
state: Colorado
city: Pueblo
country: United States
facility: St. Mary-Corwin Regional Medical Center
state: Colorado
city: Thornton
country: United States
facility: North Suburban Medical Center
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital Cancer Center
state: Georgia
city: Atlanta
country: United States
facility: Saint Joseph's Hospital of Atlanta
state: Georgia
city: Atlanta
country: United States
facility: CCOP - Atlanta Regional
state: Georgia
city: Augusta
country: United States
facility: MBCCOP - Medical College of Georgia Cancer Center
state: Georgia
city: Austell
country: United States
facility: WellStar Cobb Hospital
state: Georgia
city: Decatur
country: United States
facility: Charles B. Eberhart Cancer Center at DeKalb Medical Center
state: Georgia
city: Lawrenceville
country: United States
facility: Gwinnett Medical Center
state: Georgia
city: Marietta
country: United States
facility: Kennestone Cancer Center at Wellstar Kennestone Hospital
state: Georgia
city: Riverdale
country: United States
facility: Southern Regional Medical Center
state: Georgia
city: Aurora
country: United States
facility: Rush-Copley Cancer Care Center
state: Illinois
city: Canton
country: United States
facility: Graham Hospital
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Eureka
country: United States
facility: Eureka Community Hospital
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Clinic
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Cottage Hospital
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Hopedale
country: United States
facility: Hopedale Medical Complex
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates, Limited - West
state: Illinois
city: Kewanee
country: United States
facility: Kewanee Hospital
state: Illinois
city: Macomb
country: United States
facility: McDonough District Hospital
state: Illinois
city: Moline
country: United States
facility: Trinity Medical Center - East
state: Illinois
city: Moline
country: United States
state: Illinois
city: Normal
country: United States
facility: BroMenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center
state: Illinois
city: Ottawa
country: United States
facility: Community Hospital of Ottawa
state: Illinois
city: Ottawa
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Ottawa
state: Illinois
city: Pekin
country: United States
facility: Cancer Treatment Center at Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Peoria
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Peoria
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Community Hospital
state: Illinois
city: Spring Valley
country: United States
facility: St. Margaret's Hospital
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center at Carle Foundation Hospital
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Centers
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic, PC
state: Iowa
city: Bettendorf
country: United States
state: Iowa
city: Cedar Rapids
country: United States
facility: St. Luke's Hospital
state: Iowa
city: Cedar Rapids
country: United States
facility: Cedar Rapids Oncology Associates
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Regional Cancer Center at Mercy Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Capitol Hospital
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at John Stoddard Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at Mercy Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Lutheran Hospital
state: Iowa
city: Mason City
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - North Iowa
state: Iowa
city: Ottumwa
country: United States
facility: Ottumwa Regional Health Center Cancer Center
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Regional Cancer Center
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: West Des Moines
country: United States
facility: Medical Oncology and Hematology Associates - West Des Moines
state: Iowa
city: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Baton Rouge
country: United States
facility: Ochsner Clinic of Baton Rouge
state: Louisiana
city: Houma
country: United States
facility: Terrebonne General Medical Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Cancer Institute at Ochsner Clinic Foundation
state: Louisiana
city: Adrian
country: United States
facility: Hickman Cancer Center at Bixby Medical Center
state: Michigan
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital
state: Michigan
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Cancer Center at Oakwood Hospital and Medical Center
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Jackson
country: United States
facility: Foote Hospital
state: Michigan
city: Lambertville
country: United States
facility: Haematology-Oncology Associates of Ohio and Michigan, PC
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Monroe
country: United States
facility: Community Cancer Center of Monroe
state: Michigan
city: Monroe
country: United States
facility: Mercy Memorial Hospital System
state: Michigan
city: Saginaw
country: United States
facility: Seton Cancer Institute - Saginaw
state: Michigan
city: Warren
country: United States
facility: St. John Macomb Hospital
state: Michigan
city: Alexandria
country: United States
state: Minnesota
city: Bemidji
country: United States
facility: MeritCare Clinic - Bemidji
state: Minnesota
city: Brainerd
country: United States
facility: Brainerd Medical Center
state: Minnesota
city: Brainerd
country: United States
facility: St. Joseph's Medical Center
state: Minnesota
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Duluth
country: United States
facility: Miller-Dwan Medical Center
state: Minnesota
city: Duluth
country: United States
facility: St. Mary's - Duluth Clinic Cancer Center
state: Minnesota
city: Fergus Falls
country: United States
state: Minnesota
city: Mankato
country: United States
facility: Immanuel St. Joseph's Clinic
state: Minnesota
city: Montevideo
country: United States
facility: Chippewa County - Montevideo Hospital
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Cloud
country: United States
facility: Coborn Cancer Center
state: Minnesota
city: Sartell
country: United States
facility: Adult and Pediatric Urology, P.L.L.P.
state: Minnesota
city: St. Cloud
country: United States
facility: CentraCare Clinic - River Campus
state: Minnesota
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic, PA at Forrest General
state: Mississippi
city: Hattiesburg
country: United States
facility: Hematology & Oncology Clinic
state: Mississippi
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: St. Vincent Healthcare
state: Montana
city: Billings
country: United States
facility: Deaconess Billings Clinic - Downtown
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Hospital
state: Montana
city: Butte
country: United States
facility: St. James Community Hospital
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic
state: Montana
city: Helena
country: United States
facility: St. Peter's Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology, PLLC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Medical Oncology
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Medical Center
state: Montana
city: Missoula
country: United States
facility: Clinic of Dr. Judy L. Schmidt
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists at Montana Cancer Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
state: Montana
city: Lincoln
country: United States
facility: Cancer Resource Center - Lincoln
state: Nebraska
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Omaha
country: United States
facility: Immanuel Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Alegant Health Cancer Center at Bergan Mercy Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Creighton University Medical Center
state: Nebraska
city: Fargo
country: United States
facility: CCOP - MeritCare Hospital
state: North Dakota
city: Fargo
country: United States
facility: MeritCare Medical Group
state: North Dakota
city: Bowling Green
country: United States
facility: Wood County Oncology Center
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Medical Associates
state: Ohio
city: Fremont
country: United States
facility: Fremont Memorial Hospital
state: Ohio
city: Kenton
country: United States
facility: Kenton Oncology, Incorporated
state: Ohio
city: Lima
country: United States
facility: Lima Memorial Hospital
state: Ohio
city: Maumee
country: United States
facility: Northwest Ohio Oncology Center
state: Ohio
city: Maumee
country: United States
facility: St. Luke's Hospital
state: Ohio
city: Oregon
country: United States
facility: St. Charles Mercy Hospital
state: Ohio
city: Oregon
country: United States
facility: Toledo Clinic - Oregon
state: Ohio
city: Sandusky
country: United States
facility: Firelands Regional Medical Center
state: Ohio
city: Sandusky
country: United States
facility: North Coast Cancer Care, Incorporated
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital Cancer Center
state: Ohio
city: Tiffin
country: United States
facility: Mercy Hospital of Tiffin
state: Ohio
city: Toledo
country: United States
facility: Toledo Hospital
state: Ohio
city: Toledo
country: United States
facility: St. Vincent Mercy Medical Center
state: Ohio
city: Toledo
country: United States
facility: Medical University of Ohio Cancer Center
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic, Incorporated - Main Clinic
state: Ohio
city: Wauseon
country: United States
facility: Fulton County Health Center
state: Ohio
city: Allentown
country: United States
facility: Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
state: Pennsylvania
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Sioux Falls
country: United States
facility: Medical X-Ray Center, PC
state: South Dakota
city: Sioux Falls
country: United States
facility: Sioux Valley Hospital and University of South Dakota Medical Center
state: South Dakota
city: La Crosse
country: United States
facility: Franciscan Skemp Healthcare
state: Wisconsin
city: Sheridan
country: United States
facility: Welch Cancer Center at Sheridan Memorial Hospital
state: Wyoming
Study officials:
affiliation: Mayo Clinic
name: Debra Barton, RN, PhD, AOCN, FAAN
role: STUDY_CHAIR
References: