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Clinical Trials (PDQ®)

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

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase III, Phase IIBiomarker/Laboratory analysis, TreatmentActive18 and overNCI, OtherGOG-0286B
NCI-2013-02284, U10CA180868, U10CA027469, NCT02065687

Trial Description

Summary

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.

Further Study Information

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 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.

II. To correlate expression of the metformin transporter proteins (i.e., organic cation transporters [OCT] 1-3, multidrug and toxin extrusion [MATE] 1/2 and plasma membrane monoamine transporter [PMAT]) and key targets of the metformin/mammalian target of rapamycin (mTOR) signaling pathway with treatment response to metformin/paclitaxel/carboplatin.

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

IV. 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) 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 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.

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

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 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)

Trial Contact Information

Trial Lead Organizations/Sponsors

Gynecologic Oncology Group

National Cancer Institute

Victoria Bae-JumpPrincipal Investigator

Trial Sites

U.S.A.
Alabama
  Birmingham
 UAB Comprehensive Cancer Center
 Warner Huh Ph: 205-934-0309
Arizona
  Phoenix
 St. Joseph's Hospital and Medical Center
 John H Farley Ph: 877-602-4111
California
  Los Angeles
 Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
 Bobbie J Rimel Ph: 310-423-3348
  Email: paula.anastasia@cshs.org
  Mountain View
 Palo Alto Medical Foundation
 Albert L Pisani Ph: 650-934-7000
  Orange
 St. Joseph Hospital Regional Cancer Center - Orange
 Leslie M Randall-Whitis Ph: 877-827-8839
  Email: ucstudy@uci.edu
  Stanford
 Stanford Cancer Center
 Oliver Dorigo Ph: 650-498-7061
  Email: ccto-office@stanford.edu
  Sylmar
 Olive View - UCLA Medical Center Foundation
 Christine Holschneider Ph: 888-798-0719
Connecticut
  Hartford
 Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
 Philip J. Stella Ph: 734-712-4673
  New Britain
 George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus
 James S. Hoffman Ph: 860-224-5660
Georgia
  Decatur
 Charles B. Eberhart Cancer Center at DeKalb Medical Center
 Cyril O Spann Ph: 404-501-3279
  Gainesville
 Northeast Georgia Medical Center
 Andrew E Green Ph: 770-219-8800
  Email: cancerpatient.navigator@nghs.com
  Savannah
 Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
 William Edward Richards Ph: 800-622-6877
  Email: uchealthnews@uc.edu
Idaho
  Boise
 Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
 Philip J. Stella Ph: 734-712-4673
Illinois
  Chicago
 University of Chicago Cancer Research Center
 Meaghan E Tenney Ph: 773-834-7424
  Email: julie-traylor@ouhsc.edu
  New Lennox
 Silver Cross Hospital
 Meaghan E Tenney Ph: 773-834-7424
  Email: julie-traylor@ouhsc.edu
Indiana
  Elkhart
 Michiana Hematology-Oncology, PC - Elkhart
 Michael W. Method Ph: 574-237-1328
  Indianapolis
 St. Vincent Oncology Center
 Gregory P. Sutton Ph: 317-338-2194
  Mishawaka
 Michiana Hematology-Oncology, PC - Mishawaka
 Michael W. Method Ph: 574-237-1328
 Saint Joseph's Medical Center
 Michael W. Method Ph: 574-237-1328
  South Bend
 Michiana Hematology-Oncology, PC - South Bend
 Michael W. Method Ph: 574-237-1328
  Westville
 Michiana Hematology Oncology-PC Westville
 Michael W. Method Ph: 574-237-1328
Iowa
  Ames
 McFarland Clinic, PC
 Joseph James Merchant Ph: 515-239-2621
 William R. Bliss Cancer Center at Mary Greeley Medical Center
 Joseph James Merchant Ph: 515-239-2621
  Boone
 McFarland Clinic PC-Boone
 Joseph James Merchant Ph: 515-239-2621
  Fort Dodge
 Trinity Regional Medical Center
 Joseph James Merchant Ph: 515-239-2621
  Iowa City
 Holden Comprehensive Cancer Center at University of Iowa
 David P Bender Ph: 800-237-1225
  Jefferson
 McFarland Clinic PC-Jefferson
 Joseph James Merchant Ph: 515-239-2621
  Marshalltown
 McFarland Clinic PC-Marshalltown
 Joseph James Merchant Ph: 515-239-2621
Kentucky
  Lexington
 University of Kentucky Chandler Medical Center
 Frederick Ueland Ph: 859-257-3379
Maine
  Scarborough
 Maine Medical Center- Scarborough Campus
 Christopher J Darus Ph: 207-885-7565
Maryland
  Baltimore
 Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
 Mark A Miller Ph: 877-441-7957
  Email: pridgely@lifebridgehealth.org
 Greater Baltimore Medical Center Cancer Center
 Paul Celano Ph: 443-849-3706
Massachusetts
  Lowell
 Lowell General Hospital
 Blair Ardman Ph: 978-788-7084
  Email: ghincks@lowellgeneral.org
Michigan
  Ann Arbor
 Saint Joseph Mercy Cancer Center
 Philip J. Stella Ph: 734-712-4673
  Dearborn
 Oakwood Cancer Center at Oakwood Hospital and Medical Center
 Philip J. Stella Ph: 734-712-4673
  Detroit
 Wayne State University
 Robert T. Morris Ph: 313-576-9363
  Farmington Hills
 Weisberg Cancer Treatment Center
 Robert T. Morris Ph: 313-576-9363
  Flint
 Genesys Hurley Cancer Institute
 Philip J. Stella Ph: 734-712-4673
 Hurley Medical Center
 Philip J. Stella Ph: 734-712-4673
  Jackson
 Gayle M. Jacob Cancer Center at Allegiance Health
 Philip J. Stella Ph: 734-712-4673
  Kalamazoo
 West Michigan Cancer Center
 Sunil Nagpal Ph: 269-373-7458
  Lansing
 Sparrow Regional Cancer Center
 Philip J. Stella Ph: 734-712-4673
  Livonia
 St. Mary Mercy Hospital
 Philip J. Stella Ph: 734-712-4673
  Pontiac
 St. Joseph Mercy Oakland
 Philip J. Stella Ph: 734-712-4673
  Port Huron
 Mercy Regional Cancer Center at Mercy Hospital
 Philip J. Stella Ph: 734-712-4673
  Saginaw
 Seton Cancer Institute at Saint Mary's - Saginaw
 Philip J. Stella Ph: 734-712-4673
  Warren
 St. John Macomb Hospital
 Philip J. Stella Ph: 734-712-4673
Mississippi
  Jackson
 St. Dominic Cancer Center
 Donald P Seago Ph: 601-200-3300
Missouri
  Rolla
 Phelps County Regional Medical Center
 Jay W Carlson Ph: 800-821-7532
  Email: sherrijr@iora.org
  Saint Louis
 David C. Pratt Cancer Center at St. John's Mercy
 Jay W Carlson Ph: 800-821-7532
  Email: sherrijr@iora.org
 Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
 David Gardner Mutch Ph: 800-600-3606
  Email: info@ccadmin.wustl.edu
  Springfield
 Hulston Cancer Center at Cox Medical Center South
 Jay W Carlson Ph: 800-821-7532
  Email: sherrijr@iora.org
 St. John's Regional Health Center
 Jay W Carlson Ph: 800-821-7532
  Email: sherrijr@iora.org
Nebraska
  Omaha
 Methodist Estabrook Cancer Center
 Peter C. Morris Ph: 402-354-7939
  Email: kathryn.bartz@nmhs.org
Nevada
  Las Vegas
 Women's Cancer Center - La Canada
 Nick M. Spirtos Ph: 702-851-4672
  Reno
 Renown Institute for Cancer at Renown Regional Medical Center
 Peter C Lim Ph: 866-513-8227
 Peter C Lim Ph: 866-513-8227
New Hampshire
  Lebanon
 Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
 Leslie R. DeMars Ph: 800-639-6918
  Email: cancer.research.nurse@dartmouth.edu
New Jersey
  Mount Holly
 Virtua Fox Chase Health Cancer Program at Virtua Memorial Hospital Burlington County
 Randolph B Deger Ph: 888-847-8823
  Voorhees
 Fox Chase Virtua Health Cancer Program at Virtua West Jersey
 Randolph B Deger Ph: 888-847-8823
New York
  Albany
 Women's Cancer Care Associates
 Daniel Casey Kredentser Ph: 518-458-1390
  New York
 Memorial Sloan-Kettering Cancer Center
 Carol Aghajanian Ph: 212-639-7202
 Mount Sinai Medical Center
 Monica P Hayes Ph: 212-824-7320
  Email: jenny.figueroa@mssm.edu
North Carolina
  Chapel Hill
 Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
 Linda Van Le Ph: 877-668-0683
  Email: cancerclinicaltrials@med.unc.edu
  Charlotte
 Blumenthal Cancer Center at Carolinas Medical Center
 Robert Victor Higgins Ph: 704-355-2884
  Concord
 Batte Cancer Center at Northeast Medical Center
 Robert Victor Higgins Ph: 704-355-2884
  Durham
 Duke Cancer Institute
 Angeles Alvarez Secord Ph: 888-275-3853
  Winston-Salem
 Wake Forest University Comprehensive Cancer Center
 Samuel S. Lentz Ph: 336-713-6771
Ohio
  Akron
 Summa Center for Cancer Care at Akron City Hospital
 Vivian von Gruenigen Ph: 330-375-6101
  Cleveland
 Case Comprehensive Cancer Center
 Steven E. Waggoner Ph: 800-641-2422
 Cleveland Clinic Cancer Center at Fairview Hospital
 Peter Graham Rose Ph: 866-223-8100
 Cleveland Clinic Taussig Cancer Center
 Peter Graham Rose Ph: 866-223-8100
  Columbus
 Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
 David M O'Malley Ph: 866-627-7616
  Email: osu@emergingmed.com
  Mayfield Heights
 Hillcrest Cancer Center at Hillcrest Hospital
 Peter Graham Rose Ph: 866-223-8100
Oklahoma
  Oklahoma City
 Oklahoma University Cancer Institute
 Robert S. Mannel Ph: 405-271-4272
  Email: julie-traylor@ouhsc.edu
  Tulsa
 Cancer Care Associates-Yale
 Robert S. Mannel Ph: 405-271-4272
  Email: julie-traylor@ouhsc.edu
Pennsylvania
  Abington
 Rosenfeld Cancer Center at Abington Memorial Hospital
 Parviz Hanjani Ph: 215-481-2402
  Philadelphia
 Abramson Cancer Center of the University of Pennsylvania
 Robert A. Burger Ph: 215-746-7406
 Fox Chase Cancer Center - Philadelphia
 Angela Jain Ph: 215-728-4790
  West Reading
 McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
 Bernice L Robinson-Bennett Ph: 610-988-9323
Rhode Island
  Providence
 Women and Infants Hospital of Rhode Island
 Paul A. DiSilvestro Ph: 401-274-1122
South Carolina
  Charleston
 Hollings Cancer Center at Medical University of South Carolina
 Whitney S Graybill Ph: 843-792-9321
South Dakota
  Rapid City
 Black Hills Obstetrics & Gynecology LLP
 Helen L. Frederickson Ph: 605-343-9224
 Rapid City Regional Hospital
 Helen L. Frederickson Ph: 605-343-9224
Texas
  Dallas
 Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
 David Scott Miller Ph: 214-648-7097
Utah
  Salt Lake City
 Huntsman Cancer Institute at University of Utah
 Theresa L Werner Ph: 801-581-4477
  Email: clinical.trials@hci.utah.edu
Virginia
  Charlottesville
 University of Virginia Cancer Center
 Susan C Modesitt Ph: 434-243-6143
  Richmond
 Virginia Commonwealth University Massey Cancer Center
 Jori S Carter Ph: 804-628-1939

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT02065687
ClinicalTrials.gov processed this data on September 16, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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