Paclitaxel and Carboplatin With or Without Metformin Hydrochloride in Treating Patients With Stage III, IV, or Recurrent Endometrial Cancer
Endometrial Adenocarcinoma, Endometrial Clear Cell Adenocarcinoma, Endometrial Serous Adenocarcinoma
About this trial
This is an interventional treatment trial for Endometrial Adenocarcinoma
Eligibility Criteria
Inclusion Criteria:
Patients must have measurable stage III, measurable stage IVA, stage IVB (with or without measurable disease) or recurrent (with or without measurable disease) endometrial carcinoma
Histologic confirmation of the original primary tumor is required; patients with the following histologic epithelial cell types are eligible:
- Endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.)
- Measurable disease is defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1); measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
- Patients must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
- Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl
- Platelets greater than or equal to 100,000/mcl
- Creatinine less than 1.4 mg/dl
- Bilirubin less than or equal to 1.5 x institutional/laboratory upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x ULN
- Alkaline phosphatase less than or equal to 2.5 x ULN
- Patients must NOT have received prior chemotherapy or targeted therapy, including chemotherapy used for radiation sensitization for treatment of endometrial carcinoma
- Patients may have received prior radiation therapy for treatment of endometrial carcinoma; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy; all radiation therapy must be completed at least 4 weeks prior to the first date of study therapy
- Patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least one week prior to the first date of study therapy
- Patients must be able to swallow and retain orally-administered medication
- Patients must have signed an approved informed consent and authorization permitting release of personal health information; individuals with impaired decision-making capacity are not eligible to participate on the study
Exclusion Criteria:
- Patients must NOT be taking metformin or have been on metformin in the past 6 months
- Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer are excluded if there is any evidence of other malignancy being present within the last three years
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients who are pregnant or nursing; if patients are of reproductive age and have not undergone hysterectomy, they must use an effective contraceptive method for the duration of this study
- Any condition associated with increased risk of metformin-associated lactic acidosis; (e.g. congestive heart failure defined as New York Heart Association [NYHA] class III or IV functional status, history of acidosis of any type; habitual intake of 3 or more alcoholic beverages per day)
Sites / Locations
- University of Alabama at Birmingham Cancer Center
- Tennessee Valley Gynecologic Oncology
- Cancer Center at Saint Joseph's
- Saint Joseph's Hospital and Medical Center
- Arizona Oncology Associates-Biltmore Cancer Center
- Arizona Oncology Associates-West Orange Grove
- Arizona Oncology Associates-Wilmot
- Banner University Medical Center - Tucson
- University of Arizona Cancer Center-North Campus
- University of Arkansas for Medical Sciences
- John Muir Medical Center-Concord Campus
- UC San Diego Moores Cancer Center
- Kaiser Permanente Los Angeles Medical Center
- Los Angeles County-USC Medical Center
- USC / Norris Comprehensive Cancer Center
- Cedars Sinai Medical Center
- UCLA / Jonsson Comprehensive Cancer Center
- Palo Alto Medical Foundation-Gynecologic Oncology
- Kaiser Permanente-Oakland
- Saint Joseph Hospital - Orange
- UC Irvine Health/Chao Family Comprehensive Cancer Center
- Palo Alto Medical Foundation Health Care
- Stanford Cancer Institute Palo Alto
- Keck Medical Center of USC Pasadena
- Kaiser Permanente-Roseville
- University of California Davis Comprehensive Cancer Center
- Kaiser Permanente - Sacramento
- Zuckerberg San Francisco General Hospital
- California Pacific Medical Center-Pacific Campus
- Kaiser Permanente-San Francisco
- UCSF Medical Center-Mount Zion
- UCSF Medical Center-Mission Bay
- Kaiser Permanente-Santa Teresa-San Jose
- Kaiser Permanente San Leandro
- Kaiser Permanente Medical Center - Santa Clara
- Palo Alto Medical Foundation-Santa Cruz
- Kaiser Permanente-South San Francisco
- Palo Alto Medical Foundation-Sunnyvale
- Olive View-University of California Los Angeles Medical Center
- Kaiser Permanente-Vallejo
- Kaiser Permanente-Walnut Creek
- John Muir Medical Center-Walnut Creek
- University of Colorado Hospital
- Penrose-Saint Francis Healthcare
- Poudre Valley Hospital
- Smilow Cancer Hospital-Derby Care Center
- Smilow Cancer Hospital Care Center-Fairfield
- Smilow Cancer Hospital Care Center - Guiford
- Hartford Hospital
- Smilow Cancer Hospital Care Center at Saint Francis
- Midstate Medical Center
- The Hospital of Central Connecticut
- Yale University
- Yale-New Haven Hospital North Haven Medical Center
- Smilow Cancer Hospital-Orange Care Center
- Smilow Cancer Hospital-Torrington Care Center
- Smilow Cancer Hospital Care Center-Trumbull
- Smilow Cancer Hospital-Waterbury Care Center
- Christiana Gynecologic Oncology LLC
- Helen F Graham Cancer Center
- Medical Oncology Hematology Consultants PA
- Christiana Care Health System-Christiana Hospital
- Beebe Health Campus
- Christiana Care Health System-Wilmington Hospital
- University of Florida Health Science Center - Gainesville
- AdventHealth Orlando
- Women's Cancer Associates
- Sarasota Memorial Hospital
- Emory University Hospital Midtown
- Emory University Hospital/Winship Cancer Institute
- Northside Hospital
- Augusta University Medical Center
- Dekalb Medical Center
- Northeast Georgia Medical Center-Gainesville
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
- Pali Momi Medical Center
- Queen's Cancer Center - Pearlridge
- The Cancer Center of Hawaii-Pali Momi
- Hawaii Cancer Care Inc - Waterfront Plaza
- Queen's Medical Center
- Straub Clinic and Hospital
- University of Hawaii Cancer Center
- Hawaii Cancer Care Inc-Liliha
- Kuakini Medical Center
- Queen's Cancer Center - Kuakini
- The Cancer Center of Hawaii-Liliha
- Kapiolani Medical Center for Women and Children
- Wilcox Memorial Hospital and Kauai Medical Clinic
- Saint Alphonsus Cancer Care Center-Boise
- Northwest Community Hospital
- Rush - Copley Medical Center
- Illinois CancerCare-Bloomington
- Illinois CancerCare-Canton
- Illinois CancerCare-Carthage
- Northwestern University
- Rush University Medical Center
- University of Chicago Comprehensive Cancer Center
- Carle on Vermilion
- Cancer Care Specialists of Illinois - Decatur
- Decatur Memorial Hospital
- Carle Physician Group-Effingham
- Crossroads Cancer Center
- AMITA Health Alexian Brothers Medical Center
- Illinois CancerCare-Eureka
- NorthShore University HealthSystem-Evanston Hospital
- Illinois CancerCare-Galesburg
- Northwestern Medicine Cancer Center Delnor
- NorthShore University HealthSystem-Glenbrook Hospital
- NorthShore University HealthSystem-Highland Park Hospital
- Sudarshan K Sharma MD Limited-Gynecologic Oncology
- Illinois CancerCare-Kewanee Clinic
- Illinois CancerCare-Macomb
- Carle Physician Group-Mattoon/Charleston
- UC Comprehensive Cancer Center at Silver Cross
- Cancer Care Center of O'Fallon
- University of Chicago Medicine-Orland Park
- Illinois CancerCare-Ottawa Clinic
- Illinois CancerCare-Pekin
- Illinois CancerCare-Peoria
- Illinois CancerCare-Peru
- Illinois CancerCare-Princeton
- North Shore Medical Center
- Central Illinois Hematology Oncology Center
- Southern Illinois University School of Medicine
- Springfield Clinic
- Memorial Medical Center
- Carle Cancer Center
- The Carle Foundation Hospital
- Northwestern Medicine Cancer Center Warrenville
- Rush-Copley Healthcare Center
- Michiana Hematology Oncology PC-Crown Point
- Michiana Hematology Oncology PC-Elkhart
- Elkhart General Hospital
- Indiana University/Melvin and Bren Simon Cancer Center
- Saint Vincent Hospital and Health Care Center
- IU Health La Porte Hospital
- Franciscan Saint Anthony Health-Michigan City
- Woodland Cancer Care Center
- Michiana Hematology Oncology PC-Mishawaka
- Saint Joseph Regional Medical Center-Mishawaka
- Michiana Hematology Oncology PC-South Bend
- Michiana Hematology Oncology PC-Westville
- Mary Greeley Medical Center
- McFarland Clinic PC - Ames
- McFarland Clinic PC-Boone
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West Lakes
- Medical Oncology and Hematology Associates-Laurel
- Mercy Medical Center - Des Moines
- McFarland Clinic PC-Trinity Cancer Center
- University of Iowa/Holden Comprehensive Cancer Center
- McFarland Clinic PC-Jefferson
- McFarland Clinic PC-Marshalltown
- Mercy Medical Center - North Iowa
- Saint Elizabeth Medical Center South
- Saint Elizabeth Fort Thomas
- University of Kentucky/Markey Cancer Center
- Woman's Hospital
- Ochsner Medical Center Jefferson
- Maine Medical Center- Scarborough Campus
- Greater Baltimore Medical Center
- Sinai Hospital of Baltimore
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Walter Reed National Military Medical Center
- Tufts Medical Center
- Brigham and Women's Hospital
- Beth Israel Deaconess Medical Center
- Dana-Farber Cancer Institute
- Lowell General Hospital
- Baystate Medical Center
- UMass Memorial Medical Center - Memorial Division
- Michigan Cancer Research Consortium NCORP
- Saint Joseph Mercy Hospital
- University of Michigan Comprehensive Cancer Center
- Bronson Battle Creek
- Beaumont Hospital - Dearborn
- Wayne State University/Karmanos Cancer Institute
- Green Bay Oncology - Escanaba
- Weisberg Cancer Treatment Center
- Genesys Hurley Cancer Institute
- Hurley Medical Center
- Helen DeVos Children's Hospital at Spectrum Health
- Mercy Health Saint Mary's
- Spectrum Health at Butterworth Campus
- Green Bay Oncology - Iron Mountain
- Allegiance Health
- West Michigan Cancer Center
- Sparrow Hospital
- Saint Mary Mercy Hospital
- Monroe Cancer Center
- Mercy Health Mercy Campus
- Saint Joseph Mercy Oakland
- Lake Huron Medical Center
- Spectrum Health Reed City Hospital
- William Beaumont Hospital-Royal Oak
- Ascension Saint Mary's Hospital
- Munson Medical Center
- William Beaumont Hospital - Troy
- Saint John Macomb-Oakland Hospital
- Sanford Joe Lueken Cancer Center
- Mercy Hospital
- Fairview Southdale Hospital
- Abbott-Northwestern Hospital
- University of Minnesota/Masonic Cancer Center
- Mayo Clinic in Rochester
- Metro Minnesota Community Oncology Research Consortium
- Park Nicollet Clinic - Saint Louis Park
- United Hospital
- Lakeview Hospital
- Minnesota Oncology Hematology PA-Woodbury
- Saint Dominic-Jackson Memorial Hospital
- University of Mississippi Medical Center
- Saint Francis Medical Center
- Delbert Day Cancer Institute at PCRMC
- Mercy Clinic-Rolla-Cancer and Hematology
- Barnes-Jewish Hospital
- Washington University School of Medicine
- Mercy Hospital Saint Louis
- Cancer Research for the Ozarks NCORP
- Mercy Hospital Springfield
- CoxHealth South Hospital
- Billings Clinic Cancer Center
- Benefis Healthcare- Sletten Cancer Institute
- Kalispell Regional Medical Center
- CHI Health Saint Francis
- CHI Health Good Samaritan
- Nebraska Methodist Hospital
- University of Nebraska Medical Center
- Women's Cancer Center of Nevada
- Center of Hope at Renown Medical Center
- Renown Regional Medical Center
- Wentworth-Douglass Hospital
- Dartmouth Hitchcock Medical Center
- Memorial Sloan Kettering Basking Ridge
- Cooper Hospital University Medical Center
- Memorial Sloan Kettering Monmouth
- Morristown Medical Center
- Virtua Memorial
- Overlook Hospital
- MD Anderson Cancer Center at Cooper-Voorhees
- Virtua Voorhees
- University of New Mexico Cancer Center
- Southwest Gynecologic Oncology Associates Inc
- Women's Cancer Care Associates LLC
- Montefiore Medical Center-Einstein Campus
- Montefiore Medical Center-Weiler Hospital
- Montefiore Medical Center - Moses Campus
- State University of New York Downstate Medical Center
- New York-Presbyterian/Brooklyn Methodist Hospital
- Roswell Park Cancer Institute
- Memorial Sloan Kettering Commack
- Glens Falls Hospital
- Memorial Sloan Kettering Westchester
- NYU Winthrop Hospital
- Mount Sinai Union Square
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- Mount Sinai Hospital
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- Memorial Sloan Kettering Cancer Center
- Memorial Sloan Kettering Sleepy Hollow
- Stony Brook University Medical Center
- Memorial Sloan Kettering Nassau
- Westchester Medical Center
- Dickstein Cancer Treatment Center
- UNC Lineberger Comprehensive Cancer Center
- Carolinas Medical Center/Levine Cancer Institute
- Novant Health Presbyterian Medical Center
- Southeastern Medical Oncology Center-Clinton
- Atrium Health Cabarrus/LCI-Concord
- Duke University Medical Center
- Southeastern Medical Oncology Center-Goldsboro
- Wayne Memorial Hospital
- AdventHealth Hendersonville
- Onslow Memorial Hospital
- Southeastern Medical Oncology Center-Jacksonville
- Novant Health Cancer Institute - Kernersville
- Novant Health Cancer Institute - Mount Airy
- FirstHealth of the Carolinas-Moore Regional Hospital
- Duke Raleigh Hospital
- Novant Health Cancer Institute - Statesville
- Novant Health Cancer Institute - Thomasville
- Novant Health Cancer Institute - Wilkesboro
- New Hanover Regional Medical Center/Zimmer Cancer Center
- Novant Health Oncology Specialists
- Winston-Salem Health Care
- Wake Forest University Health Sciences
- Sanford Bismarck Medical Center
- Sanford Broadway Medical Center
- Sanford Clinic North-Fargo
- Sanford Roger Maris Cancer Center
- Summa Health System - Akron Campus
- University of Cincinnati Cancer Center-UC Medical Center
- Good Samaritan Hospital - Cincinnati
- Bethesda North Hospital
- Case Western Reserve University
- Cleveland Clinic Cancer Center/Fairview Hospital
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- Riverside Methodist Hospital
- Columbus NCI Community Oncology Research Program
- The Mark H Zangmeister Center
- Grandview Hospital
- Good Samaritan Hospital - Dayton
- Miami Valley Hospital
- Miami Valley Hospital North
- Hillcrest Hospital Cancer Center
- UH Seidman Cancer Center at Lake Health Mentor Campus
- ProMedica Flower Hospital
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
- Wright-Patterson Medical Center
- University of Oklahoma Health Sciences Center
- Oklahoma Cancer Specialists and Research Institute-Tulsa
- Jefferson Abington Hospital
- Saint Luke's University Hospital-Bethlehem Campus
- Geisinger Medical Center
- Adams Cancer Center
- UPMC Cancer Centers - Arnold Palmer Pavilion
- Cherry Tree Cancer Center
- Geisinger Medical Center-Cancer Center Hazleton
- Geisinger Medical Oncology-Lewisburg
- Lewistown Hospital
- University of Pennsylvania/Abramson Cancer Center
- Thomas Jefferson University Hospital
- Fox Chase Cancer Center
- Temple University Hospital
- UPMC-Magee Womens Hospital
- University of Pittsburgh Cancer Institute (UPCI)
- UPMC-Passavant Hospital
- Geisinger Cancer Services-Pottsville
- UPMC Cancer Center at UPMC Northwest
- Geisinger Medical Group
- UPMC Uniontown Hospital Radiation Oncology
- Chester County Hospital
- Reading Hospital
- Geisinger Wyoming Valley/Henry Cancer Center
- WellSpan Health-York Hospital
- Women and Infants Hospital
- AnMed Health Cancer Center
- Medical University of South Carolina
- Saint Francis Hospital
- Gibbs Cancer Center-Pelham
- Carolina Blood and Cancer Care Associates PA-Lancaster
- Carolina Blood and Cancer Care Associates PA
- Spartanburg Medical Center
- Black Hills Obstetrics and Gynecology
- Rapid City Regional Hospital
- Sanford Cancer Center Oncology Clinic
- Avera Cancer Institute
- Sanford USD Medical Center - Sioux Falls
- Chattanooga's Program in Women's Oncology
- University of Tennessee - Knoxville
- Dell Seton Medical Center at The University of Texas
- Texas Oncology-Austin Midtown
- Texas Oncology - Central Austin Cancer Center
- Texas Oncology - South Austin Cancer Center
- Texas Oncology Bedford
- MD Anderson in The Woodlands
- Texas Health Presbyterian Hospital Dallas
- Parkland Memorial Hospital
- Texas Oncology at Baylor Charles A Sammons Cancer Center
- UT Southwestern/Simmons Cancer Center-Dallas
- Texas Oncology - Fort Worth Cancer Center
- Lyndon Baines Johnson General Hospital
- Houston Methodist Hospital
- M D Anderson Cancer Center
- Memorial Hermann Texas Medical Center
- Methodist Willowbrook Hospital
- MD Anderson West Houston
- MD Anderson League City
- Texas Oncology-Longview Cancer Center
- MD Anderson in Sugar Land
- Houston Methodist Sugar Land Hospital
- Texas Oncology Cancer Center Sugar Land
- Texas Oncology-The Woodlands
- Tyler Cancer Center
- Deke Slayton Cancer Center
- American Fork Hospital / Huntsman Intermountain Cancer Center
- Sandra L Maxwell Cancer Center
- Logan Regional Hospital
- Intermountain Medical Center
- McKay-Dee Hospital Center
- Utah Valley Regional Medical Center
- Dixie Medical Center Regional Cancer Center
- Utah Cancer Specialists-Salt Lake City
- Huntsman Cancer Institute/University of Utah
- LDS Hospital
- Southwestern Vermont Medical Center
- Central Vermont Medical Center/National Life Cancer Treatment
- University of Vermont Medical Center
- University of Vermont and State Agricultural College
- Norris Cotton Cancer Center-North
- University of Virginia Cancer Center
- Inova Schar Cancer Institute
- Inova Fairfax Hospital
- Henrico Doctor's Hospital
- Virginia Gynecologic Oncology
- Virginia Commonwealth University/Massey Cancer Center
- Carilion Clinic Gynecological Oncology
- Highline Medical Center-Main Campus
- MultiCare Gig Harbor Medical Park
- Fred Hutchinson Cancer Research Center
- Seattle Cancer Care Alliance
- University of Washington Medical Center - Northwest
- Women's Cancer Center of Seattle
- University of Washington Medical Center - Montlake
- MultiCare Tacoma General Hospital
- Edwards Comprehensive Cancer Center
- Monongalia Hospital
- Marshfield Clinic-Chippewa Center
- Marshfield Clinic Cancer Center at Sacred Heart
- Green Bay Oncology at Saint Vincent Hospital
- Saint Vincent Hospital Cancer Center Green Bay
- Green Bay Oncology Limited at Saint Mary's Hospital
- Saint Vincent Hospital Cancer Center at Saint Mary's
- University of Wisconsin Hospital and Clinics
- Holy Family Memorial Hospital
- Marshfield Medical Center-Marshfield
- Medical College of Wisconsin
- ProHealth D N Greenwald Center
- ProHealth Oconomowoc Memorial Hospital
- Saint Vincent Hospital Cancer Center at Oconto Falls
- Marshfield Medical Center-Rice Lake
- Marshfield Clinic Stevens Point Center
- Saint Vincent Hospital Cancer Center at Sturgeon Bay
- Green Bay Oncology - Sturgeon Bay
- ProHealth Waukesha Memorial Hospital
- UW Cancer Center at ProHealth Care
- Aspirus Regional Cancer Center
- Marshfield Clinic-Wausau Center
- Marshfield Medical Center - Weston
- Marshfield Clinic - Wisconsin Rapids Center
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Arm I (paclitaxel, carboplatin, metformin hydrochloride)
Arm II (paclitaxel, carboplatin, placebo)
Patients receive paclitaxel IV over 3 hours on day 1, carboplatin IV over 30 minutes on day 1, and metformin hydrochloride PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising metformin hydrochloride PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. In both arms, patients who achieve SD or PR and still have measurable disease at the completion of course 6 may continue to receive paclitaxel IV and carboplatin IV (with metformin hydrochloride or placebo) for an additional 4 courses at the discretion of the treating investigator.
Patients receive paclitaxel IV and carboplatin IV as in Arm I. Patients also receive placebo PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising placebo PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. In both arms, patients who achieve SD or PR and still have measurable disease at the completion of course 6 may continue to receive paclitaxel IV and carboplatin IV (with metformin hydrochloride or placebo) for an additional 4 courses at the discretion of the treating investigator.