Paclitaxel and Carboplatin With or Without Metformin Hydrochloride in Treating Patients With Stage III, IV, or Recurrent Endometrial Cancer

September 28, 2021 updated by: Gynecologic Oncology Group

A Randomized Phase II/III Study of Paclitaxel/Carboplatin/Metformin (NSC#91485) Versus Paclitaxel/Carboplatin/Placebo as Initial Therapy for Measurable Stage III or IVA, Stage IVB, or Recurrent Endometrial Cancer

This randomized phase II/III trial studies how well paclitaxel, carboplatin, and metformin hydrochloride works and compares it to paclitaxel, carboplatin, and placebo in treating patients with endometrial cancer that is stage III, IV, or has come back. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Metformin hydrochloride may help paclitaxel and carboplatin work better by making cancer cells more sensitive to the drugs. It is not yet known whether paclitaxel and carboplatin is more effective with or without metformin hydrochloride in treating endometrial cancer.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine if the addition of metformin (metformin hydrochloride) to the standard regimen of carboplatin and paclitaxel prolongs progression-free survival (PFS) in women with advanced or recurrent endometrial cancer. (Phase II) II. To determine if the addition of metformin to the standard regimen of carboplatin and paclitaxel prolongs overall survival (OS) in the same population if a phase III study is conducted. Both clinical trials (Phase II and III) will utilize OS as a primary endpoint if a phase III trial is opened.

SECONDARY OBJECTIVES:

I. To estimate the proportion of patients with objective response (response rate [RR]) in the population of patients with measurable disease by treatment.

II. To estimate the duration of response in the population of patients with measurable disease who respond by treatment.

III. To estimate overall survival (OS) and relative hazards of death for each treatment arm if the study stops after the phase II trial is completed. If the study continues with a phase III clinical trial, then PFS will be a secondary endpoint.

IV. To determine the nature, frequency and degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) for each treatment arm.

V. To estimate possible differences in RR, PFS, OS, and toxicity rates for the treatment regimens by the patients' level of obesity.

TERTIARY OBJECTIVES:

I. To test whether PIK3CA mutations/amplifications, PTEN mutations or PIK3R1/PIK3R2 mutations have a lower hazard of progression or death (PFS endpoint) among patients who are treated with metformin.

II. To test whether higher expression of MATE 2 is associated with a lower hazard of progression or death (PFS endpoint) among patients who are treated with metformin.

III. To explore the association of metabolic factors (i.e. body mass index [BMI], hip-to-waist ratio, diabetes status, hemoglobin A1c [HgbA1C], fasting insulin and glucose levels, homeostatic model assessment [HOMA] scores) with treatment response to metformin/paclitaxel/carboplatin, PFS, and OS.

IV. To test whether genomic profiles (i.e. PIK3CA mutations/amplifications, PTEN mutations or PIK3R1/PIK3R2 mutations) differ between the tumors of obese and non-obese endometrial cancer (EC) patients.

V. To correlate expression of key targets of the insulin/IGF-1/mTOR signaling pathway (p-IGF1R, p-S6 and p-4EBP-1) with treatment response to metformin/paclitaxel/carboplatin, PFS, OS and obesity status.

VI. To determine if the genetic variants of the metformin transporters correspond with treatment response to metformin/paclitaxel/carboplatin, PFS and OS.

VII. To estimate differences in physical functioning, physical activity, and fatigue between treatment arms.

VIII. To explore the association between metabolic factors (i.e., BMI, hip-to-waist ratio, diabetes status, HgbA1C, fasting insulin and glucose levels, HOMA scores) and physical functioning, physical activity, and fatigue.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours on day 1, carboplatin IV over 30 minutes on day 1, and metformin hydrochloride orally (PO) twice daily (BID) (approximately 10-12 hours apart) on days 1-21 (once daily [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.

ARM II: Patients receive paclitaxel IV and carboplatin IV as in Arm I. Patients also receive placebo PO BID (approximately 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 stable disease (SD) or partial response (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.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Study Type

Interventional

Enrollment (Actual)

469

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham Cancer Center
      • Huntsville, Alabama, United States, 35805
        • Tennessee Valley Gynecologic Oncology
    • Arizona
      • Phoenix, Arizona, United States, 85004
        • Cancer Center at Saint Joseph's
      • Phoenix, Arizona, United States, 85013
        • Saint Joseph's Hospital and Medical Center
      • Phoenix, Arizona, United States, 85016
        • Arizona Oncology Associates-Biltmore Cancer Center
      • Tucson, Arizona, United States, 85719
        • Banner University Medical Center - Tucson
      • Tucson, Arizona, United States, 85719
        • University of Arizona Cancer Center-North Campus
      • Tucson, Arizona, United States, 85704
        • Arizona Oncology Associates-West Orange Grove
      • Tucson, Arizona, United States, 85710
        • Arizona Oncology Associates-Wilmot
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
    • California
      • Concord, California, United States, 94520
        • John Muir Medical Center-Concord Campus
      • La Jolla, California, United States, 92093
        • UC San Diego Moores Cancer Center
      • Los Angeles, California, United States, 90033
        • USC / Norris Comprehensive Cancer Center
      • Los Angeles, California, United States, 90033
        • Los Angeles County-USC Medical Center
      • Los Angeles, California, United States, 90095
        • UCLA / Jonsson Comprehensive Cancer Center
      • Los Angeles, California, United States, 90027
        • Kaiser Permanente Los Angeles Medical Center
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center
      • Mountain View, California, United States, 94040
        • Palo Alto Medical Foundation-Gynecologic Oncology
      • Oakland, California, United States, 94611
        • Kaiser Permanente-Oakland
      • Orange, California, United States, 92868
        • UC Irvine Health/Chao Family Comprehensive Cancer Center
      • Orange, California, United States, 92868
        • Saint Joseph Hospital - Orange
      • Palo Alto, California, United States, 94304
        • Stanford Cancer Institute Palo Alto
      • Palo Alto, California, United States, 94301
        • Palo Alto Medical Foundation Health Care
      • Pasadena, California, United States, 91105
        • Keck Medical Center of USC Pasadena
      • Roseville, California, United States, 95661
        • Kaiser Permanente-Roseville
      • Sacramento, California, United States, 95817
        • University of California Davis Comprehensive Cancer Center
      • Sacramento, California, United States, 95825
        • Kaiser Permanente - Sacramento
      • San Francisco, California, United States, 94115
        • Kaiser Permanente-San Francisco
      • San Francisco, California, United States, 94158
        • UCSF Medical Center-Mission Bay
      • San Francisco, California, United States, 94115
        • California Pacific Medical Center-Pacific Campus
      • San Francisco, California, United States, 94115
        • UCSF Medical Center-Mount Zion
      • San Francisco, California, United States, 94110
        • Zuckerberg San Francisco General Hospital
      • San Jose, California, United States, 95119
        • Kaiser Permanente-Santa Teresa-San Jose
      • San Leandro, California, United States, 94577
        • Kaiser Permanente San Leandro
      • Santa Clara, California, United States, 95051
        • Kaiser Permanente Medical Center - Santa Clara
      • Santa Cruz, California, United States, 95065
        • Palo Alto Medical Foundation-Santa Cruz
      • South San Francisco, California, United States, 94080
        • Kaiser Permanente-South San Francisco
      • Sunnyvale, California, United States, 94086
        • Palo Alto Medical Foundation-Sunnyvale
      • Sylmar, California, United States, 91342
        • Olive View-University of California Los Angeles Medical Center
      • Vallejo, California, United States, 94589
        • Kaiser Permanente-Vallejo
      • Walnut Creek, California, United States, 94596
        • Kaiser Permanente-Walnut Creek
      • Walnut Creek, California, United States, 94598
        • John Muir Medical Center-Walnut Creek
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Hospital
      • Colorado Springs, Colorado, United States, 80907
        • Penrose-Saint Francis Healthcare
      • Fort Collins, Colorado, United States, 80524
        • Poudre Valley Hospital
    • Connecticut
      • Derby, Connecticut, United States, 06418
        • Smilow Cancer Hospital-Derby Care Center
      • Fairfield, Connecticut, United States, 06824
        • Smilow Cancer Hospital Care Center-Fairfield
      • Guilford, Connecticut, United States, 06437
        • Smilow Cancer Hospital Care Center - Guiford
      • Hartford, Connecticut, United States, 06105
        • Smilow Cancer Hospital Care Center at Saint Francis
      • Hartford, Connecticut, United States, 06102
        • Hartford Hospital
      • Meriden, Connecticut, United States, 06451
        • Midstate Medical Center
      • New Britain, Connecticut, United States, 06050
        • The Hospital of Central Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale University
      • North Haven, Connecticut, United States, 06473
        • Yale-New Haven Hospital North Haven Medical Center
      • Orange, Connecticut, United States, 06477
        • Smilow Cancer Hospital-Orange Care Center
      • Torrington, Connecticut, United States, 06790
        • Smilow Cancer Hospital-Torrington Care Center
      • Trumbull, Connecticut, United States, 06611
        • Smilow Cancer Hospital Care Center-Trumbull
      • Waterbury, Connecticut, United States, 06708
        • Smilow Cancer Hospital-Waterbury Care Center
    • Delaware
      • Newark, Delaware, United States, 19713
        • Helen F Graham Cancer Center
      • Newark, Delaware, United States, 19713
        • Medical Oncology Hematology Consultants PA
      • Newark, Delaware, United States, 19718
        • Christiana Care Health System-Christiana Hospital
      • Newark, Delaware, United States, 19713
        • Christiana Gynecologic Oncology LLC
      • Rehoboth Beach, Delaware, United States, 19971
        • Beebe Health Campus
      • Wilmington, Delaware, United States, 19801
        • Christiana Care Health System-Wilmington Hospital
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida Health Science Center - Gainesville
      • Orlando, Florida, United States, 32803
        • AdventHealth Orlando
      • Saint Petersburg, Florida, United States, 33713
        • Women's Cancer Associates
      • Sarasota, Florida, United States, 34239
        • Sarasota Memorial Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Emory University Hospital Midtown
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital/Winship Cancer Institute
      • Atlanta, Georgia, United States, 30342
        • Northside Hospital
      • Augusta, Georgia, United States, 30912
        • Augusta University Medical Center
      • Decatur, Georgia, United States, 30033
        • Dekalb Medical Center
      • Gainesville, Georgia, United States, 30501
        • Northeast Georgia Medical Center-Gainesville
      • Savannah, Georgia, United States, 31405
        • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
    • Hawaii
      • 'Aiea, Hawaii, United States, 96701
        • Pali Momi Medical Center
      • 'Aiea, Hawaii, United States, 96701
        • Queen's Cancer Center - Pearlridge
      • 'Aiea, Hawaii, United States, 96701
        • The Cancer Center of Hawaii-Pali Momi
      • Honolulu, Hawaii, United States, 96813
        • Queen's Medical Center
      • Honolulu, Hawaii, United States, 96817
        • The Cancer Center of Hawaii-Liliha
      • Honolulu, Hawaii, United States, 96813
        • Hawaii Cancer Care Inc - Waterfront Plaza
      • Honolulu, Hawaii, United States, 96813
        • Straub Clinic and Hospital
      • Honolulu, Hawaii, United States, 96813
        • University of Hawaii Cancer Center
      • Honolulu, Hawaii, United States, 96817
        • Hawaii Cancer Care Inc-Liliha
      • Honolulu, Hawaii, United States, 96817
        • Kuakini Medical Center
      • Honolulu, Hawaii, United States, 96817
        • Queen's Cancer Center - Kuakini
      • Honolulu, Hawaii, United States, 96826
        • Kapiolani Medical Center for Women and Children
      • Lihue, Hawaii, United States, 96766
        • Wilcox Memorial Hospital and Kauai Medical Clinic
    • Idaho
      • Boise, Idaho, United States, 83706
        • Saint Alphonsus Cancer Care Center-Boise
    • Illinois
      • Arlington Heights, Illinois, United States, 60005
        • Northwest Community Hospital
      • Aurora, Illinois, United States, 60504
        • Rush - Copley Medical Center
      • Bloomington, Illinois, United States, 61704
        • Illinois CancerCare-Bloomington
      • Canton, Illinois, United States, 61520
        • Illinois CancerCare-Canton
      • Carthage, Illinois, United States, 62321
        • Illinois CancerCare-Carthage
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
      • Danville, Illinois, United States, 61832
        • Carle on Vermilion
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
      • Decatur, Illinois, United States, 62526
        • Cancer Care Specialists of Illinois - Decatur
      • Effingham, Illinois, United States, 62401
        • Crossroads Cancer Center
      • Effingham, Illinois, United States, 62401
        • Carle Physician Group-Effingham
      • Elk Grove Village, Illinois, United States, 60007
        • AMITA Health Alexian Brothers Medical Center
      • Eureka, Illinois, United States, 61530
        • Illinois CancerCare-Eureka
      • Evanston, Illinois, United States, 60201
        • NorthShore University HealthSystem-Evanston Hospital
      • Galesburg, Illinois, United States, 61401
        • Illinois CancerCare-Galesburg
      • Geneva, Illinois, United States, 60134
        • Northwestern Medicine Cancer Center Delnor
      • Glenview, Illinois, United States, 60026
        • NorthShore University HealthSystem-Glenbrook Hospital
      • Highland Park, Illinois, United States, 60035
        • NorthShore University HealthSystem-Highland Park Hospital
      • Hinsdale, Illinois, United States, 60521
        • Sudarshan K Sharma MD Limited-Gynecologic Oncology
      • Kewanee, Illinois, United States, 61443
        • Illinois CancerCare-Kewanee Clinic
      • Macomb, Illinois, United States, 61455
        • Illinois CancerCare-Macomb
      • Mattoon, Illinois, United States, 61938
        • Carle Physician Group-Mattoon/Charleston
      • New Lenox, Illinois, United States, 60451
        • UC Comprehensive Cancer Center at Silver Cross
      • O'Fallon, Illinois, United States, 62269
        • Cancer Care Center of O'Fallon
      • Orland Park, Illinois, United States, 60462
        • University of Chicago Medicine-Orland Park
      • Ottawa, Illinois, United States, 61350
        • Illinois CancerCare-Ottawa Clinic
      • Pekin, Illinois, United States, 61554
        • Illinois CancerCare-Pekin
      • Peoria, Illinois, United States, 61615
        • Illinois CancerCare-Peoria
      • Peru, Illinois, United States, 61354
        • Illinois CancerCare-Peru
      • Princeton, Illinois, United States, 61356
        • Illinois CancerCare-Princeton
      • Skokie, Illinois, United States, 60076
        • North Shore Medical Center
      • Springfield, Illinois, United States, 62781
        • Memorial Medical Center
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University School of Medicine
      • Springfield, Illinois, United States, 62702
        • Springfield Clinic
      • Springfield, Illinois, United States, 62702
        • Central Illinois Hematology Oncology Center
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
      • Urbana, Illinois, United States, 61801
        • The Carle Foundation Hospital
      • Warrenville, Illinois, United States, 60555
        • Northwestern Medicine Cancer Center Warrenville
      • Yorkville, Illinois, United States, 60560
        • Rush-Copley Healthcare Center
    • Indiana
      • Crown Point, Indiana, United States, 46307
        • Michiana Hematology Oncology PC-Crown Point
      • Elkhart, Indiana, United States, 46515
        • Elkhart General Hospital
      • Elkhart, Indiana, United States, 46514
        • Michiana Hematology Oncology PC-Elkhart
      • Indianapolis, Indiana, United States, 46202
        • Indiana University/Melvin and Bren Simon Cancer Center
      • Indianapolis, Indiana, United States, 46260
        • Saint Vincent Hospital and Health Care Center
      • La Porte, Indiana, United States, 46350
        • IU Health La Porte Hospital
      • Michigan City, Indiana, United States, 46360
        • Franciscan Saint Anthony Health-Michigan City
      • Michigan City, Indiana, United States, 46360
        • Woodland Cancer Care Center
      • Mishawaka, Indiana, United States, 46545
        • Michiana Hematology Oncology PC-Mishawaka
      • Mishawaka, Indiana, United States, 46545
        • Saint Joseph Regional Medical Center-Mishawaka
      • South Bend, Indiana, United States, 46601
        • Michiana Hematology Oncology PC-South Bend
      • Westville, Indiana, United States, 46391
        • Michiana Hematology Oncology PC-Westville
    • Iowa
      • Ames, Iowa, United States, 50010
        • McFarland Clinic PC - Ames
      • Ames, Iowa, United States, 50010
        • Mary Greeley Medical Center
      • Boone, Iowa, United States, 50036
        • McFarland Clinic PC-Boone
      • Clive, Iowa, United States, 50325
        • Mercy Cancer Center-West Lakes
      • Clive, Iowa, United States, 50325
        • Medical Oncology and Hematology Associates-West Des Moines
      • Des Moines, Iowa, United States, 50314
        • Mercy Medical Center - Des Moines
      • Des Moines, Iowa, United States, 50314
        • Medical Oncology and Hematology Associates-Laurel
      • Fort Dodge, Iowa, United States, 50501
        • McFarland Clinic PC-Trinity Cancer Center
      • Iowa City, Iowa, United States, 52242
        • University of Iowa/Holden Comprehensive Cancer Center
      • Jefferson, Iowa, United States, 50129
        • McFarland Clinic PC-Jefferson
      • Marshalltown, Iowa, United States, 50158
        • McFarland Clinic PC-Marshalltown
      • Mason City, Iowa, United States, 50401
        • Mercy Medical Center - North Iowa
    • Kentucky
      • Edgewood, Kentucky, United States, 41017
        • Saint Elizabeth Medical Center South
      • Fort Thomas, Kentucky, United States, 41075
        • Saint Elizabeth Fort Thomas
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky/Markey Cancer Center
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70817
        • Woman's Hospital
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Medical Center Jefferson
    • Maine
      • Scarborough, Maine, United States, 04074
        • Maine Medical Center- Scarborough Campus
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University/Sidney Kimmel Cancer Center
      • Baltimore, Maryland, United States, 21215
        • Sinai Hospital of Baltimore
      • Baltimore, Maryland, United States, 21204
        • Greater Baltimore Medical Center
      • Bethesda, Maryland, United States, 20889-5600
        • Walter Reed National Military Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
      • Lowell, Massachusetts, United States, 01854
        • Lowell General Hospital
      • Springfield, Massachusetts, United States, 01199
        • Baystate Medical Center
      • Worcester, Massachusetts, United States, 01605
        • UMass Memorial Medical Center - Memorial Division
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center
      • Ann Arbor, Michigan, United States, 48106
        • Saint Joseph Mercy Hospital
      • Ann Arbor, Michigan, United States, 48106
        • Michigan Cancer Research Consortium NCORP
      • Battle Creek, Michigan, United States, 49017
        • Bronson Battle Creek
      • Dearborn, Michigan, United States, 48124
        • Beaumont Hospital - Dearborn
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
      • Escanaba, Michigan, United States, 49829
        • Green Bay Oncology - Escanaba
      • Farmington Hills, Michigan, United States, 48334
        • Weisberg Cancer Treatment Center
      • Flint, Michigan, United States, 48503
        • Hurley Medical Center
      • Flint, Michigan, United States, 48503
        • Genesys Hurley Cancer Institute
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health at Butterworth Campus
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital at Spectrum Health
      • Grand Rapids, Michigan, United States, 49503
        • Mercy Health Saint Mary's
      • Iron Mountain, Michigan, United States, 49801
        • Green Bay Oncology - Iron Mountain
      • Jackson, Michigan, United States, 49201
        • Allegiance Health
      • Kalamazoo, Michigan, United States, 49007
        • West Michigan Cancer Center
      • Lansing, Michigan, United States, 48912
        • Sparrow Hospital
      • Livonia, Michigan, United States, 48154
        • Saint Mary Mercy Hospital
      • Monroe, Michigan, United States, 48162
        • Monroe Cancer Center
      • Muskegon, Michigan, United States, 49444
        • Mercy Health Mercy Campus
      • Pontiac, Michigan, United States, 48341
        • Saint Joseph Mercy Oakland
      • Port Huron, Michigan, United States, 48060
        • Lake Huron Medical Center
      • Reed City, Michigan, United States, 49677
        • Spectrum Health Reed City Hospital
      • Royal Oak, Michigan, United States, 48073
        • William Beaumont Hospital-Royal Oak
      • Saginaw, Michigan, United States, 48601
        • Ascension Saint Mary's Hospital
      • Traverse City, Michigan, United States, 49684
        • Munson Medical Center
      • Troy, Michigan, United States, 48085
        • William Beaumont Hospital - Troy
      • Warren, Michigan, United States, 48093
        • Saint John Macomb-Oakland Hospital
    • Minnesota
      • Bemidji, Minnesota, United States, 56601
        • Sanford Joe Lueken Cancer Center
      • Coon Rapids, Minnesota, United States, 55433
        • Mercy Hospital
      • Edina, Minnesota, United States, 55435
        • Fairview Southdale Hospital
      • Minneapolis, Minnesota, United States, 55407
        • Abbott-Northwestern Hospital
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota/Masonic Cancer Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester
      • Saint Louis Park, Minnesota, United States, 55416
        • Park Nicollet Clinic - Saint Louis Park
      • Saint Louis Park, Minnesota, United States, 55416
        • Metro Minnesota Community Oncology Research Consortium
      • Saint Paul, Minnesota, United States, 55102
        • United Hospital
      • Stillwater, Minnesota, United States, 55082
        • Lakeview Hospital
      • Woodbury, Minnesota, United States, 55125
        • Minnesota Oncology Hematology PA-Woodbury
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
      • Jackson, Mississippi, United States, 39216
        • Saint Dominic-Jackson Memorial Hospital
    • Missouri
      • Cape Girardeau, Missouri, United States, 63703
        • Saint Francis Medical Center
      • Rolla, Missouri, United States, 65401
        • Delbert Day Cancer Institute at PCRMC
      • Rolla, Missouri, United States, 65401
        • Mercy Clinic-Rolla-Cancer and Hematology
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, United States, 63110
        • Barnes-Jewish Hospital
      • Saint Louis, Missouri, United States, 63141
        • Mercy Hospital Saint Louis
      • Springfield, Missouri, United States, 65804
        • Cancer Research for the Ozarks NCORP
      • Springfield, Missouri, United States, 65807
        • CoxHealth South Hospital
      • Springfield, Missouri, United States, 65804
        • Mercy Hospital Springfield
    • Montana
      • Billings, Montana, United States, 59101
        • Billings Clinic Cancer Center
      • Great Falls, Montana, United States, 59405
        • Benefis Healthcare- Sletten Cancer Institute
      • Kalispell, Montana, United States, 59901
        • Kalispell Regional Medical Center
    • Nebraska
      • Grand Island, Nebraska, United States, 68803
        • CHI Health Saint Francis
      • Kearney, Nebraska, United States, 68847
        • CHI Health Good Samaritan
      • Omaha, Nebraska, United States, 68114
        • Nebraska Methodist Hospital
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Women's Cancer Center of Nevada
      • Reno, Nevada, United States, 89502
        • Renown Regional Medical Center
      • Reno, Nevada, United States, 89502
        • Center of Hope at Renown Medical Center
    • New Hampshire
      • Dover, New Hampshire, United States, 03820
        • Wentworth-Douglass Hospital
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Memorial Sloan Kettering Basking Ridge
      • Camden, New Jersey, United States, 08103
        • Cooper Hospital University Medical Center
      • Middletown, New Jersey, United States, 07748
        • Memorial Sloan Kettering Monmouth
      • Morristown, New Jersey, United States, 07960
        • Morristown Medical Center
      • Mount Holly, New Jersey, United States, 08060
        • Virtua Memorial
      • Summit, New Jersey, United States, 07902
        • Overlook Hospital
      • Voorhees, New Jersey, United States, 08043
        • Virtua Voorhees
      • Voorhees, New Jersey, United States, 08043
        • MD Anderson Cancer Center at Cooper-Voorhees
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • University of New Mexico Cancer Center
      • Albuquerque, New Mexico, United States, 87106
        • Southwest Gynecologic Oncology Associates Inc
    • New York
      • Albany, New York, United States, 12208
        • Women's Cancer Care Associates LLC
      • Bronx, New York, United States, 10461
        • Montefiore Medical Center-Einstein Campus
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center - Moses Campus
      • Bronx, New York, United States, 10461
        • Montefiore Medical Center-Weiler Hospital
      • Brooklyn, New York, United States, 11215
        • New York-Presbyterian/Brooklyn Methodist Hospital
      • Brooklyn, New York, United States, 11203
        • State University of New York Downstate Medical Center
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • Commack, New York, United States, 11725
        • Memorial Sloan Kettering Commack
      • Glens Falls, New York, United States, 12801
        • Glens Falls Hospital
      • Harrison, New York, United States, 10604
        • Memorial Sloan Kettering Westchester
      • Mineola, New York, United States, 11501
        • NYU Winthrop Hospital
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10029
        • Mount Sinai Hospital
      • New York, New York, United States, 10032
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
      • New York, New York, United States, 10003
        • Mount Sinai Union Square
      • Sleepy Hollow, New York, United States, 10591
        • Memorial Sloan Kettering Sleepy Hollow
      • Stony Brook, New York, United States, 11794
        • Stony Brook University Medical Center
      • Uniondale, New York, United States, 11553
        • Memorial Sloan Kettering Nassau
      • Valhalla, New York, United States, 10595
        • Westchester Medical Center
      • White Plains, New York, United States, 10601
        • Dickstein Cancer Treatment Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • UNC Lineberger Comprehensive Cancer Center
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Medical Center/Levine Cancer Institute
      • Charlotte, North Carolina, United States, 28204
        • Novant Health Presbyterian Medical Center
      • Clinton, North Carolina, United States, 28328
        • Southeastern Medical Oncology Center-Clinton
      • Concord, North Carolina, United States, 28025
        • Atrium Health Cabarrus/LCI-Concord
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Goldsboro, North Carolina, United States, 27534
        • Southeastern Medical Oncology Center-Goldsboro
      • Goldsboro, North Carolina, United States, 27534
        • Wayne Memorial Hospital
      • Hendersonville, North Carolina, United States, 28792
        • AdventHealth Hendersonville
      • Jacksonville, North Carolina, United States, 28546
        • Southeastern Medical Oncology Center-Jacksonville
      • Jacksonville, North Carolina, United States, 28546
        • Onslow Memorial Hospital
      • Kernersville, North Carolina, United States, 27284
        • Novant Health Cancer Institute - Kernersville
      • Mount Airy, North Carolina, United States, 27030
        • Novant Health Cancer Institute - Mount Airy
      • Pinehurst, North Carolina, United States, 28374
        • FirstHealth of the Carolinas-Moore Regional Hospital
      • Raleigh, North Carolina, United States, 27609
        • Duke Raleigh Hospital
      • Statesville, North Carolina, United States, 28625
        • Novant Health Cancer Institute - Statesville
      • Thomasville, North Carolina, United States, 27360
        • Novant Health Cancer Institute - Thomasville
      • Wilkesboro, North Carolina, United States, 28659
        • Novant Health Cancer Institute - Wilkesboro
      • Wilmington, North Carolina, United States, 28401
        • New Hanover Regional Medical Center/Zimmer Cancer Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
      • Winston-Salem, North Carolina, United States, 27103
        • Novant Health Oncology Specialists
      • Winston-Salem, North Carolina, United States, 27103
        • Winston-Salem Health Care
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
        • Sanford Bismarck Medical Center
      • Fargo, North Dakota, United States, 58122
        • Sanford Roger Maris Cancer Center
      • Fargo, North Dakota, United States, 58122
        • Sanford Broadway Medical Center
      • Fargo, North Dakota, United States, 58122
        • Sanford Clinic North-Fargo
    • Ohio
      • Akron, Ohio, United States, 44304
        • Summa Health System - Akron Campus
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Cancer Center-UC Medical Center
      • Cincinnati, Ohio, United States, 45220
        • Good Samaritan Hospital - Cincinnati
      • Cincinnati, Ohio, United States, 45242
        • Bethesda North Hospital
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Cleveland, Ohio, United States, 44111
        • Cleveland Clinic Cancer Center/Fairview Hospital
      • Columbus, Ohio, United States, 43214
        • Riverside Methodist Hospital
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
      • Columbus, Ohio, United States, 43219
        • The Mark H Zangmeister Center
      • Columbus, Ohio, United States, 43215
        • Columbus NCI Community Oncology Research Program
      • Dayton, Ohio, United States, 45406
        • Good Samaritan Hospital - Dayton
      • Dayton, Ohio, United States, 45409
        • Miami Valley Hospital
      • Dayton, Ohio, United States, 45415
        • Miami Valley Hospital North
      • Dayton, Ohio, United States, 45405
        • Grandview Hospital
      • Mayfield Heights, Ohio, United States, 44124
        • Hillcrest Hospital Cancer Center
      • Mentor, Ohio, United States, 44060
        • UH Seidman Cancer Center at Lake Health Mentor Campus
      • Sylvania, Ohio, United States, 43560
        • ProMedica Flower Hospital
      • Toledo, Ohio, United States, 43606
        • ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
      • Wright-Patterson Air Force Base, Ohio, United States, 45433
        • Wright-Patterson Medical Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
      • Tulsa, Oklahoma, United States, 74146
        • Oklahoma Cancer Specialists and Research Institute-Tulsa
    • Pennsylvania
      • Abington, Pennsylvania, United States, 19001
        • Jefferson Abington Hospital
      • Bethlehem, Pennsylvania, United States, 18015
        • Saint Luke's University Hospital-Bethlehem Campus
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Medical Center
      • Gettysburg, Pennsylvania, United States, 17325
        • Adams Cancer Center
      • Greensburg, Pennsylvania, United States, 15601
        • UPMC Cancer Centers - Arnold Palmer Pavilion
      • Hanover, Pennsylvania, United States, 17331
        • Cherry Tree Cancer Center
      • Hazleton, Pennsylvania, United States, 18201
        • Geisinger Medical Center-Cancer Center Hazleton
      • Lewisburg, Pennsylvania, United States, 17837
        • Geisinger Medical Oncology-Lewisburg
      • Lewistown, Pennsylvania, United States, 17044
        • Lewistown Hospital
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania/Abramson Cancer Center
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University Hospital
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC-Magee Womens Hospital
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Cancer Institute (UPCI)
      • Pittsburgh, Pennsylvania, United States, 15237
        • UPMC-Passavant Hospital
      • Pottsville, Pennsylvania, United States, 17901
        • Geisinger Cancer Services-Pottsville
      • Seneca, Pennsylvania, United States, 16346
        • UPMC Cancer Center at UPMC Northwest
      • State College, Pennsylvania, United States, 16801
        • Geisinger Medical Group
      • Uniontown, Pennsylvania, United States, 15401
        • UPMC Uniontown Hospital Radiation Oncology
      • West Chester, Pennsylvania, United States, 19380
        • Chester County Hospital
      • West Reading, Pennsylvania, United States, 19611
        • Reading Hospital
      • Wilkes-Barre, Pennsylvania, United States, 18711
        • Geisinger Wyoming Valley/Henry Cancer Center
      • York, Pennsylvania, United States, 17403
        • WellSpan Health-York Hospital
    • Rhode Island
      • Providence, Rhode Island, United States, 02905
        • Women and Infants Hospital
    • South Carolina
      • Anderson, South Carolina, United States, 29621
        • AnMed Health Cancer Center
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Greenville, South Carolina, United States, 29601
        • Saint Francis Hospital
      • Greer, South Carolina, United States, 29651
        • Gibbs Cancer Center-Pelham
      • Lancaster, South Carolina, United States, 29720
        • Carolina Blood and Cancer Care Associates PA-Lancaster
      • Rock Hill, South Carolina, United States, 29732
        • Carolina Blood and Cancer Care Associates PA
      • Spartanburg, South Carolina, United States, 29303
        • Spartanburg Medical Center
    • South Dakota
      • Rapid City, South Dakota, United States, 57701
        • Rapid City Regional Hospital
      • Rapid City, South Dakota, United States, 57701
        • Black Hills Obstetrics and Gynecology
      • Sioux Falls, South Dakota, United States, 57105
        • Avera Cancer Institute
      • Sioux Falls, South Dakota, United States, 57117-5134
        • Sanford USD Medical Center - Sioux Falls
      • Sioux Falls, South Dakota, United States, 57104
        • Sanford Cancer Center Oncology Clinic
    • Tennessee
      • Chattanooga, Tennessee, United States, 37403
        • Chattanooga's Program in Women's Oncology
      • Knoxville, Tennessee, United States, 37920
        • University of Tennessee - Knoxville
    • Texas
      • Austin, Texas, United States, 78701
        • Dell Seton Medical Center at The University of Texas
      • Austin, Texas, United States, 78705
        • Texas Oncology-Austin Midtown
      • Austin, Texas, United States, 78731
        • Texas Oncology - Central Austin Cancer Center
      • Austin, Texas, United States, 78745
        • Texas Oncology - South Austin Cancer Center
      • Bedford, Texas, United States, 76022
        • Texas Oncology Bedford
      • Conroe, Texas, United States, 77384
        • MD Anderson in The Woodlands
      • Dallas, Texas, United States, 75235
        • Parkland Memorial Hospital
      • Dallas, Texas, United States, 75390
        • UT Southwestern/Simmons Cancer Center-Dallas
      • Dallas, Texas, United States, 75246
        • Texas Oncology at Baylor Charles A Sammons Cancer Center
      • Dallas, Texas, United States, 75231
        • Texas Health Presbyterian Hospital Dallas
      • Fort Worth, Texas, United States, 76104
        • Texas Oncology - Fort Worth Cancer Center
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center
      • Houston, Texas, United States, 77026-1967
        • Lyndon Baines Johnson General Hospital
      • Houston, Texas, United States, 77030
        • Houston Methodist Hospital
      • Houston, Texas, United States, 77030
        • Memorial Hermann Texas Medical Center
      • Houston, Texas, United States, 77070
        • Methodist Willowbrook Hospital
      • Houston, Texas, United States, 77079
        • MD Anderson West Houston
      • League City, Texas, United States, 77573
        • MD Anderson League City
      • Longview, Texas, United States, 75601
        • Texas Oncology-Longview Cancer Center
      • Sugar Land, Texas, United States, 77478
        • MD Anderson in Sugar Land
      • Sugar Land, Texas, United States, 77479
        • Houston Methodist Sugar Land Hospital
      • Sugar Land, Texas, United States, 77479
        • Texas Oncology Cancer Center Sugar Land
      • The Woodlands, Texas, United States, 77380
        • Texas Oncology-The Woodlands
      • Tyler, Texas, United States, 75702
        • Tyler Cancer Center
      • Webster, Texas, United States, 77598
        • Deke Slayton Cancer Center
    • Utah
      • American Fork, Utah, United States, 84003
        • American Fork Hospital / Huntsman Intermountain Cancer Center
      • Cedar City, Utah, United States, 84720
        • Sandra L Maxwell Cancer Center
      • Logan, Utah, United States, 84321
        • Logan Regional Hospital
      • Murray, Utah, United States, 84107
        • Intermountain Medical Center
      • Ogden, Utah, United States, 84403
        • McKay-Dee Hospital Center
      • Provo, Utah, United States, 84604
        • Utah Valley Regional Medical Center
      • Saint George, Utah, United States, 84770
        • Dixie Medical Center Regional Cancer Center
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute/University of Utah
      • Salt Lake City, Utah, United States, 84106
        • Utah Cancer Specialists-Salt Lake City
      • Salt Lake City, Utah, United States, 84143
        • LDS Hospital
    • Vermont
      • Bennington, Vermont, United States, 05201
        • Southwestern Vermont Medical Center
      • Berlin, Vermont, United States, 05602
        • Central Vermont Medical Center/National Life Cancer Treatment
      • Burlington, Vermont, United States, 05401
        • University of Vermont Medical Center
      • Burlington, Vermont, United States, 05405
        • University of Vermont and State Agricultural College
      • Saint Johnsbury, Vermont, United States, 05819
        • Norris Cotton Cancer Center-North
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Cancer Center
      • Fairfax, Virginia, United States, 22031
        • Inova Schar Cancer Institute
      • Falls Church, Virginia, United States, 22042
        • Inova Fairfax Hospital
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University/Massey Cancer Center
      • Richmond, Virginia, United States, 23229
        • Virginia Gynecologic Oncology
      • Richmond, Virginia, United States, 23229
        • Henrico Doctor's Hospital
      • Roanoke, Virginia, United States, 24016
        • Carilion Clinic Gynecological Oncology
    • Washington
      • Burien, Washington, United States, 98166
        • Highline Medical Center-Main Campus
      • Gig Harbor, Washington, United States, 98335
        • MultiCare Gig Harbor Medical Park
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center
      • Seattle, Washington, United States, 98109
        • Seattle Cancer Care Alliance
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center - Montlake
      • Seattle, Washington, United States, 98133
        • University of Washington Medical Center - Northwest
      • Seattle, Washington, United States, 98133
        • Women's Cancer Center of Seattle
      • Tacoma, Washington, United States, 98405
        • MultiCare Tacoma General Hospital
    • West Virginia
      • Huntington, West Virginia, United States, 25701
        • Edwards Comprehensive Cancer Center
      • Morgantown, West Virginia, United States, 26505
        • Monongalia Hospital
    • Wisconsin
      • Chippewa Falls, Wisconsin, United States, 54729
        • Marshfield Clinic-Chippewa Center
      • Eau Claire, Wisconsin, United States, 54701
        • Marshfield Clinic Cancer Center at Sacred Heart
      • Green Bay, Wisconsin, United States, 54301
        • Saint Vincent Hospital Cancer Center Green Bay
      • Green Bay, Wisconsin, United States, 54303
        • Saint Vincent Hospital Cancer Center at Saint Mary's
      • Green Bay, Wisconsin, United States, 54303
        • Green Bay Oncology Limited at Saint Mary's Hospital
      • Green Bay, Wisconsin, United States, 54301-3526
        • Green Bay Oncology at Saint Vincent Hospital
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Hospital and Clinics
      • Manitowoc, Wisconsin, United States, 54221
        • Holy Family Memorial Hospital
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Medical Center-Marshfield
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin
      • Mukwonago, Wisconsin, United States, 53149
        • ProHealth D N Greenwald Center
      • Oconomowoc, Wisconsin, United States, 53066
        • ProHealth Oconomowoc Memorial Hospital
      • Oconto Falls, Wisconsin, United States, 54154
        • Saint Vincent Hospital Cancer Center at Oconto Falls
      • Rice Lake, Wisconsin, United States, 54868
        • Marshfield Medical Center-Rice Lake
      • Stevens Point, Wisconsin, United States, 54482
        • Marshfield Clinic Stevens Point Center
      • Sturgeon Bay, Wisconsin, United States, 54235-1495
        • Saint Vincent Hospital Cancer Center at Sturgeon Bay
      • Sturgeon Bay, Wisconsin, United States, 54235
        • Green Bay Oncology - Sturgeon Bay
      • Waukesha, Wisconsin, United States, 53188
        • UW Cancer Center at ProHealth Care
      • Waukesha, Wisconsin, United States, 53188
        • ProHealth Waukesha Memorial Hospital
      • Wausau, Wisconsin, United States, 54401
        • Aspirus Regional Cancer Center
      • Wausau, Wisconsin, United States, 54401
        • Marshfield Clinic-Wausau Center
      • Weston, Wisconsin, United States, 54476
        • Marshfield Medical Center - Weston
      • Wisconsin Rapids, Wisconsin, United States, 54494
        • Marshfield Clinic - Wisconsin Rapids Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm I (paclitaxel, carboplatin, metformin hydrochloride)

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.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Drug: Paclitaxel
Given IV
Other Names:
  • Taxol
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol Konzentrat
Drug: Metformin Hydrochloride
Given PO
Other Names:
  • Glucophage
  • Riomet
  • Cidophage
  • Metformin HCl
  • Glifage
  • Siofor
  • APO-Metformin
  • Dimefor
  • Glucoformin
  • Glucophage ER
ACTIVE_COMPARATOR: Arm II (paclitaxel, carboplatin, placebo)

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.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Drug: Paclitaxel
Given IV
Other Names:
  • Taxol
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol Konzentrat
Other: Placebo Administration
Given PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS) (Phase II)
Time Frame: From date of study entry to time of progression or death, whichever occurs first, assessed up to 5 years
Time until disease progression, death, or date of last contact. This study was originally designed as a phase II/III study. It passed the phase 2 threshold and started the phase 3; however, a phase 3 interim analysis stopped the trial for futility. Therefore, data available for Phase III may be identical to data reported for Phase II or Phase II/III combined.
From date of study entry to time of progression or death, whichever occurs first, assessed up to 5 years
Overall Survival (OS) (Phase II and III)
Time Frame: From date of study entry to time of death or the date of last contact, assessed up to 5 years
The observed length of life from randomization into the study to death or the date of last contact. This study was originally designed as a phase II/III study. It passed the phase 2 threshold and started the phase 3; however, a phase 3 interim analysis stopped the trial for futility. Therefore, data available for Phase III may be identical to data reported for Phase II or Phase II/III combined.
From date of study entry to time of death or the date of last contact, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Patients Responding to Therapy
Time Frame: During study treatment, up to 5 years.
The proportion of patients who had a response (complete or partial) by RECIST 1.1. Measurable disease is defined by 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 CT, 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.
During study treatment, up to 5 years.
Duration of Response by Treatment
Time Frame: From the date of response to disease progression, death, or date last seen assessed up to 5 years
Duration of response until disease progression, death, or date last seen among patients who responded.
From the date of response to disease progression, death, or date last seen assessed up to 5 years
Overall Survival (OS) (Phase II)
Time Frame: From date of study entry to time of death or the date of last contact, assessed up to 5 years.
The observed length of life from randomization into the study to death or the date of last contact. For response, only those patients who had measurable disease were included in an analysis of response. Non-measurable patients are included in the ITT analysis. This study was originally designed as a phase II/III study. It passed the phase 2 threshold and started the phase 3; however, a phase 3 interim analysis stopped the trial for futility. Therefore, data available for Phase III may be identical to data reported for Phase II or Phase II/III combined.
From date of study entry to time of death or the date of last contact, assessed up to 5 years.
Progression Free Survival (PFS) (Phase III)
Time Frame: From date of study entry to time of progression or death, whichever occurs first, assessed up to 5 years
Time until disease progression, death, or date of last contact. For response, only those patients who had measurable disease were included in an analysis of response. Non-measurable patients are included in the ITT analysis. This study was originally designed as a phase II/III study. It passed the phase 2 threshold and started the phase 3; however, a phase 3 interim analysis stopped the trial for futility. Therefore, data available for Phase III may be identical to data reported for Phase II or Phase II/III combined.
From date of study entry to time of progression or death, whichever occurs first, assessed up to 5 years
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4
Time Frame: Up to 5 years
Toxicities will be assessed by organ or organ system. For each category of toxicity, each patient will be evaluated by the worst grade experienced during the course of therapy. Data will be summarized by frequency and severity according to the regimen administered. The number of patients with a grade three or greater adverse event will be reported (by system organ class).
Up to 5 years
Level of Obesity
Time Frame: Up to 5 years
Obesity will be quantitative assessed by body mass index (BMI) and will be assessed for its predictive and prognostic significance. The interaction between BMI and metformin treatment will be examined with an interaction term in a Cox proportional hazards model.
Up to 5 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Metabolic Factor Levels
Time Frame: Up to 5 years
Hip-to-waist ratio, diabetes status, hemoglobin A1c, fasting insulin glucose levels, and homeostatic model assessment scores will be assessed for their predictive and prognostic significance. Variables will be analyzed as continuous covariates (or as appropriate with transformations such as the logarithm) with Cox models or logistic regression.
Up to 5 years
Incidence of PIK3 Mutations/Amplifications
Time Frame: Up to 5 years
PIK3CA mutations/amplifications and PIK3R1/PIK3R2 mutations will be examined for prognostic and predictive significance.
Up to 5 years
Expression of MATE 2
Time Frame: Up to 5 years
Expression will be examined by immunohistochemistry with intensity of staining and the percentage of cells staining positive. From these statistics, an H-score will be calculated. Expression will be further dichotomized as high expression and low expression at the median to maximize the power of the study.
Up to 5 years
Levels of Key Targets of the Metformin/mTOR Signaling Pathway
Time Frame: Up to 5 years
Levels before and after treatment will be assessed for their predictive and prognostic significance.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gynecologic Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Victoria L Bae-Jump, NRG Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

March 17, 2014

Primary Completion (ACTUAL)

April 17, 2019

Study Completion (ANTICIPATED)

September 13, 2023

Study Registration Dates

First Submitted

February 14, 2014

First Submitted That Met QC Criteria

February 14, 2014

First Posted (ESTIMATE)

February 19, 2014

Study Record Updates

Last Update Posted (ACTUAL)

September 30, 2021

Last Update Submitted That Met QC Criteria

September 28, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GOG-0286B (OTHER: CTEP)
  • U10CA180868 (U.S. NIH Grant/Contract)
  • U10CA027469 (U.S. NIH Grant/Contract)
  • U10CA180830 (U.S. NIH Grant/Contract)
  • NCI-2013-02284 (REGISTRY: CTRP (Clinical Trial Reporting Program))
  • s14-01068

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