Paclitaxel, Carboplatin, and Bevacizumab or Paclitaxel, Carboplatin, and Temsirolimus or Ixabepilone, Carboplatin, and Bevacizumab in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer

A Three Arm Randomized Phase II Study of Paclitaxel/Carboplatin/Bevacizumab (NSC #704865), Paclitaxel/Carboplatin/Temsirolimus (NSC #683864) and Ixabepilone (NSC #710428)/Carboplatin/Bevacizumab as Initial Therapy for Measurable Stage III or IVA, Stage IVB, or Recurrent Endometrial Cancer

This randomized phase II trial studies paclitaxel, carboplatin, and bevacizumab or paclitaxel, carboplatin, and temsirolimus or ixabepilone, carboplatin, and bevacizumab to see how well they work in treating patients with stage III, stage IV, or recurrent endometrial cancer. Drugs used in chemotherapy, such as paclitaxel, carboplatin, and ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known which treatment regimen is most effective in treating patients with endometrial cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Recurrent Malignant Uterine Corpus Neoplasm; Stage IIIA Uterine Corpus Carcinoma or Carcinosarcoma by AJCC v7 Stage; Stage IIIB Uterine Corpus Carcinoma or Carcinosarcoma by AJCC v7 Stage; Stage IIIC Uterine Corpus Carcinoma or Carcinosarcoma by AJCC v7 Stage; Stage IVA Uterine Corpus Carcinoma or Carcinosarcoma by AJCC v7 Stage; Stage IVB Uterine Corpus Carcinoma or Carcinosarcoma by AJCC v7 Stage
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Carboplatin; Drug: Paclitaxel; Biological: Bevacizumab; Drug: Ixabepilone; Drug: Temsirolimus

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the hazard of progression or death of each of the three arms relative to that of historical controls in patients with advanced or recurrent endometrial cancer.

SECONDARY OBJECTIVES:

I. To determine the nature, frequency, and maximum degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v)3.0 for each of the three arms.

II. To estimate the distribution of the duration of overall survival for each of the three arms.

III. To estimate the proportion of patients with measurable disease who have confirmed objective tumor responses by treatment.

TERTIARY OBJECTIVES:

I. Explore the associations between select biomarkers and progression-free survival as well as secondary measures of clinical outcome (overall survival, tumor response, or disease status if possible) in the context of histologic cell type and treatment.

IA. Somatic mutations in phosphatase and tensin homolog (PTEN)/ phosphoinositide-3-kinase (PI3K) and RAS pathway members by Sequenom mutational profiling and targeted sequencing of candidate genes.

IB. Microsatellite instability by analysis of five National Cancer Institute consensus microsatellite markers (BAT25, BAT26, D2S2123, D5S346, and D17S250) using the Applied Biosystems (ABI) Prism 3100 Genetic Analyzer.

IC. Copy number alterations (gains or losses) by array comparative genomic hybridization (aCGH).

ID. Tumor expression of PTEN and class III beta-tubulin using immunohistochemistry.

IE. Concentration of vascular endothelial growth factor (VEGF) in pre-cycle 1 plasma using an enzyme-linked immunosorbent assay.

II. Explore the relationship among the various biomarkers by histologic subtype and treatment.

III. Explore which combination of biomarkers and clinical covariates optimally predicts responsiveness and resistance to the three treatment arms.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours, carboplatin IV over 30 minutes, and bevacizumab* IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients undergoing treatment post-surgery (=< 12 weeks) receive bevacizumab beginning on course 2.

ARM II: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus* IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive temsirolimus IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients undergoing treatment post-surgery (=< 12 weeks) receive temsirolimus beginning on course 2.

ARM III: Patients receive ixabepilone IV over 1 hour, carboplatin IV over 30 minutes, and bevacizumab* IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients undergoing treatment post-surgery (=< 12 weeks) receive bevacizumab beginning on course 2.

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

• Study Type: Interventional
• Enrollment (Actual): 349
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Saint Joseph's Hospital and Medical Center
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center-North Campus
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • Concord, California, United States, 94520
      • John Muir Medical Center-Concord
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90095
      • UCLA / Jonsson Comprehensive Cancer Center
    • Mountain View, California, United States, 94040
      • Palo Alto Medical Foundation-Gynecologic Oncology
    • San Diego, California, United States, 92103
      • UC San Diego Medical Center - Hillcrest
    • San Diego, California, United States, 92161
      • San Diego VA Medical Center
    • San Francisco, California, United States, 94115
      • UCSF Medical Center-Mount Zion
    • Walnut Creek, California, United States, 94598
      • John Muir Medical Center-Walnut Creek
  • Colorado
    • Aurora, Colorado, United States, 80045
      • UCHealth University of Colorado Hospital
    • Englewood, Colorado, United States, 80110
      • Rocky Mountain Gynecologic Oncology PC
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Smilow Cancer Hospital Care Center at Saint Francis
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
  • Florida
    • Clearwater, Florida, United States, 33756
      • Morton Plant Hospital
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
    • Orlando, Florida, United States, 32806
      • Orlando Health Cancer Institute
    • Orlando, Florida, United States, 32803
      • AdventHealth Orlando
  • Georgia
    • Macon, Georgia, United States, 31201
      • Central Georgia Gynecologic Oncology
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
  • Hawaii
    • 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
      • 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
    • Wailuku, Hawaii, United States, 96793
      • Maui Memorial Medical Center
    • Wailuku, Hawaii, United States, 96793
      • Pacific Cancer Institute of Maui
    • ‘Aiea, Hawaii, United States, 96701
      • Pali Momi Medical Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • Rush MD Anderson Cancer Center
    • Elgin, Illinois, United States, 60123
      • Advocate Sherman Hospital
    • Hinsdale, Illinois, United States, 60521
      • Hinsdale Hematology Oncology Associates Incorporated
    • Hinsdale, Illinois, United States, 60521
      • Sudarshan K Sharma MD Limited-Gynecologic Oncology
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Elkhart, Indiana, United States, 46514
      • Michiana Hematology Oncology PC-Elkhart
    • Elkhart, Indiana, United States, 46514-2098
      • Elkhart Clinic
    • Indianapolis, Indiana, United States, 46260
      • Ascension Saint Vincent Indianapolis Hospital
    • Kokomo, Indiana, United States, 46904
      • Community Howard Regional Health
    • La Porte, Indiana, United States, 46350
      • IU Health La Porte Hospital
    • Mishawaka, Indiana, United States, 46545
      • Michiana Hematology Oncology PC-Mishawaka
    • Mishawaka, Indiana, United States, 46545
      • Saint Joseph Regional Medical Center-Mishawaka
    • Plymouth, Indiana, United States, 46563
      • Michiana Hematology Oncology PC-Plymouth
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46628
      • Northern Indiana Cancer Research Consortium
    • South Bend, Indiana, United States, 46617
      • South Bend Clinic
    • Westville, Indiana, United States, 46391
      • Michiana Hematology Oncology PC-Westville
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic - Ames
    • Clive, Iowa, United States, 50325
      • Mercy Cancer Center-West Lakes
    • Clive, Iowa, United States, 50325
      • UI Health Care Mission Cancer and Blood - West Des Moines Clinic
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50309
      • Iowa-Wide Oncology Research Coalition NCORP
    • Des Moines, Iowa, United States, 50309
      • UI Health Care Mission Cancer and Blood - Des Moines Clinic
    • Des Moines, Iowa, United States, 50314
      • UI Health Care Mission Cancer and Blood - Laurel Clinic
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
    • West Des Moines, Iowa, United States, 50266-7700
      • Methodist West Hospital
    • West Des Moines, Iowa, United States, 50266
      • Mercy Medical Center-West Lakes
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67905
      • Cancer Center of Kansas-Liberal
    • McPherson, Kansas, United States, 67460
      • Cancer Center of Kansas - McPherson
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas - Pratt
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Hospitals Wichita
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
    • Wichita, Kansas, United States, 67208
      • Associates In Womens Health
    • Wichita, Kansas, United States, 67214
      • Wichita NCI Community Oncology Research Program
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky/Markey Cancer Center
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
    • Louisville, Kentucky, United States, 40202
      • The James Graham Brown Cancer Center at University of Louisville
  • Maine
    • Portland, Maine, United States, 04102
      • MaineHealth Maine Medical Center - Portland
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • MedStar Franklin Square Medical Center/Weinberg Cancer Institute
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
    • Elkton, Maryland, United States, 21921
      • Christiana Care - Union Hospital
  • Massachusetts
    • 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, 48106
      • Michigan Cancer Research Consortium NCORP
    • Ann Arbor, Michigan, United States, 48106
      • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
    • Dearborn, Michigan, United States, 48124
      • Corewell Health Dearborn Hospital
    • Detroit, Michigan, United States, 48236
      • Henry Ford Health Saint John Hospital
    • Flint, Michigan, United States, 48532
      • Genesys Regional Medical Center-West Flint Campus
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49048
      • Beacon Kalamazoo
    • Lansing, Michigan, United States, 48912
      • University of Michigan Health - Sparrow Lansing
    • Livonia, Michigan, United States, 48154
      • Trinity Health Saint Mary Mercy Livonia Hospital
    • Niles, Michigan, United States, 49120
      • Corewell Health Lakeland Hospitals - Niles Hospital
    • Pontiac, Michigan, United States, 48341
      • Trinity Health Saint Joseph Mercy Oakland Hospital
    • Port Huron, Michigan, United States, 48060
      • Lake Huron Medical Center
    • Royal Oak, Michigan, United States, 48073
      • Corewell Health William Beaumont University Hospital
    • Saginaw, Michigan, United States, 48601
      • MyMichigan Medical Center Saginaw
    • Saint Joseph, Michigan, United States, 49085
      • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
    • Saint Joseph, Michigan, United States, 49085
      • Corewell Health Lakeland Hospitals - Saint Joseph Hospital
    • Warren, Michigan, United States, 48093
      • Henry Ford Health Warren Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
    • Jackson, Mississippi, United States, 39216
      • Saint Dominic-Jackson Memorial Hospital
    • Pascagoula, Mississippi, United States, 39581
      • Singing River Hospital
  • Missouri
    • Columbia, Missouri, United States, 65212
      • MU Health - University Hospital/Ellis Fischel Cancer Center
    • Rolla, Missouri, United States, 65401
      • Phelps Health Delbert Day Cancer Institute
    • 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
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • St Louis, Missouri, United States, 63104
      • SSM Health Saint Louis University Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • 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 Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • Mount Holly, New Jersey, United States, 08060
      • Virtua Memorial
    • Newark, New Jersey, United States, 07101
      • Rutgers New Jersey Medical School
    • Phillipsburg, New Jersey, United States, 08865
      • Saint Luke's Hospital-Warren Campus
    • Summit, New Jersey, United States, 07902
      • Overlook Hospital
    • Voorhees Township, New Jersey, United States, 08043
      • Virtua Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Southwest Gynecologic Oncology Associates Inc
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Cancer Center
  • New York
    • Albany, New York, United States, 12208
      • Women's Cancer Care Associates LLC
    • Brightwaters, New York, United States, 11718
      • Island Gynecologic Oncology
    • Brooklyn, New York, United States, 11203
      • State University of New York Downstate Medical Center
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Fresh Meadows, New York, United States, 11365
      • New York Hospital Medical Center of Queens
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Asheville, North Carolina, United States, 28816
      • Hope Women's Cancer Centers-Asheville
    • Burlington, North Carolina, United States, 27215
      • Cone Health Cancer Center at Alamance Regional
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center/Levine Cancer Institute
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Akron, Ohio, United States, 44307
      • Cleveland Clinic Akron General
    • Akron, Ohio, United States, 44304
      • Summa Health System - Akron Campus
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Cancer Center-UC Medical Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • 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
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Mentor, Ohio, United States, 44060
      • UH Seidman Cancer Center at Lake Health Mentor Campus
  • 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
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital-Cedar Crest
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Hazleton, Pennsylvania, United States, 18201
      • Geisinger Medical Center-Cancer Center Hazleton
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Milton S Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Pennsylvania Hospital
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley/Henry Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Columbia, South Carolina, United States, 29210
      • South Carolina Oncology Associates PA
  • South Dakota
    • 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
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University/Ingram Cancer Center
  • Texas
    • Dallas, Texas, United States, 75235
      • Parkland Memorial Hospital
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
    • Dallas, Texas, United States, 75390
      • Clements University Hospital
    • Galveston, Texas, United States, 77555-0565
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • Houston, Texas, United States, 77026-1967
      • Lyndon Baines Johnson General Hospital
    • Temple, Texas, United States, 76508
      • Scott and White Memorial Hospital
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center
    • Hampton, Virginia, United States, 23666
      • Virginia Oncology Associates-Hampton
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates - Norfolk
    • Richmond, Virginia, United States, 23298
      • VCU Massey Comprehensive Cancer Center
    • Roanoke, Virginia, United States, 24033
      • Carilion Roanoke Memorial Hospital
  • Washington
    • Bellingham, Washington, United States, 98226
      • PeaceHealth Medical Group PC
    • Everett, Washington, United States, 98201
      • Providence Regional Cancer Partnership
    • Mount Vernon, Washington, United States, 98274
      • Skagit Regional Health Cancer Care Center
    • Poulsbo, Washington, United States, 98370
      • Harrison HealthPartners Hematology and Oncology-Poulsbo
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center - Montlake
    • Seattle, Washington, United States, 98112
      • Kaiser Permanente Washington
    • Seattle, Washington, United States, 98104
      • Pacific Gynecology Specialists
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center
    • Seattle, Washington, United States, 98133
      • University of Washington Medical Center - Northwest
    • Sequim, Washington, United States, 98384
      • Olympic Medical Cancer Care Center
    • Silverdale, Washington, United States, 98383
      • Saint Joseph Medical Center Hematology and Oncology - Silverdale
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Spokane, Washington, United States, 99204
      • MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
    • Tacoma, Washington, United States, 98405
      • MultiCare Tacoma General Hospital
    • Tacoma, Washington, United States, 98405
      • Saint Joseph Medical Center
    • Walla Walla, Washington, United States, 99362
      • Providence Saint Mary Regional Cancer Center
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital and Clinics
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center - University Hospital
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53233
      • Aurora Sinai Medical Center
    • Oshkosh, Wisconsin, United States, 54904
      • Vince Lombardi Cancer Clinic - Oshkosh
    • Sheboygan, Wisconsin, United States, 53081
      • Vince Lombardi Cancer Clinic-Sheboygan
    • West Allis, Wisconsin, United States, 53227
      • Aurora West Allis Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

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.), mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma
• 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 Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
• Patients must not be eligible for a higher priority GOG protocol, if one exists; in general, this would refer to any active GOG Phase III protocol or Rare Tumor protocol for the same patient population
• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl equivalent to Common Terminology Criteria (CTCAE v3.0) grade 1
• Platelets greater than or equal to 100,000/mcl
• Creatinine less than or equal to 1.5 times institutional upper limit normal (ULN), CTCAE v3.0 grade 1
• Bilirubin less than or equal to 1.5 x ULN (CTCAE v3.0 grade 1)
• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)
• Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)

• Urine protein creatinine (UPC) ratio must be < 1.0 gram (gm); if UPC ratio >= 1, collection of 24-hour urine measurement of urine protein is recommended (24-hour urine protein level must be < 1000 mg for patient enrollment)

  • UPC ratio of spot urine is an estimation of the 24 urine protein excretion

    • A UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm
• Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) =< 1.5 x ULN
• Fasting cholesterol less than 300 mg/dL (CTCAE v3.0 grade 1)
• Fasting triglycerides =< 2.5 x ULN (CTCAE v3.0 grade 1)
• Patients must NOT have received prior chemotherapy or targeted therapy, including chemotherapy used for radiation sensitization for treatment of endometrial carcinoma
• Patients must NOT have received prior therapy with bevacizumab or other VEGF pathway targeted therapy; patients must NOT have received prior therapy with temsirolimus, everolimus, ridaforolimus, sirolimus, or any other PI3K/ v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycins (mTor) pathway targeted therapy
• Patients may have receive 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; the prior radiation field, radiation dose, number of fractions and prior radiation start and stop dates must be provided on the Fast Fact Sheet (FFS) at registration
• 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 have signed an approved informed consent and authorization permitting release of personal health information

Exclusion Criteria:

• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, and other specific malignancies as noted below, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
• Patients who have received prior chemotherapy for any abdominal or pelvic tumor within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
• Patients with serious, non-healing wound, ulcer, or bone fracture; this includes history of abdominal/pelvic fistula, gastrointestinal perforation or intra-abdominal abscess within 3 months prior to the first date of study therapy; patients with underlying lesions that caused the fistula or perforation in the past that have not been corrected
• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
• Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy or any brain metastases

• Patients with clinically significant cardiovascular disease; this includes:

  • Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg
  • Myocardial infarction or unstable angina within 6 months of the first date of study therapy
  • New York Heart Association (NYHA) class II or greater congestive heart failure
  • History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)
  • CTCAE grade 2 or greater peripheral vascular disease.
  • History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of study therapy.
  • Aortic aneurysm and/or history of aortic dissection
• Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies

• Patients undergoing invasive procedures as defined below:

  • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of bevacizumab or temsirolimus therapy
  • Major surgical procedure anticipated during the course of the study.
  • Minor surgical procedures, fine needle aspirates, or core biopsies within 7 days prior to the first date of study therapy
• Patients with known prior history of interstitial pneumonitis
• Patients with CTCAE v. 3, grade 2 or greater hypoxemia
• Patients with CTCAE v. 3, grade 2 or greater dyspnea
• Patients must not have uncontrolled diabetes, and must not have baseline hemoglobin A1C (HgbA1C) > 8
• Patients with peripheral neuropathy > CTCAE v.3, grade 1
• Patients who are pregnant or nursing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (paclitaxel, carboplatin, bevacizumab); Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	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; JM8; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Biological: Bevacizumab; Given IV; Other Names: Avastin; ABP 215; Anti-VEGF; Anti-VEGF Humanized Monoclonal Antibody; Anti-VEGF Monoclonal Antibody SIBP04; Anti-VEGF rhuMAb; Bevacizumab awwb; Bevacizumab Biosimilar ABP 215; Bevacizumab Biosimilar BEVZ92; Bevacizumab Biosimilar BI 695502; Bevacizumab Biosimilar CBT 124; Bevacizumab Biosimilar CT-P16; Bevacizumab Biosimilar FKB238; Bevacizumab Biosimilar GB-222; Bevacizumab Biosimilar HD204; Bevacizumab Biosimilar HLX04; Bevacizumab Biosimilar IBI305; Bevacizumab Biosimilar LY01008; Bevacizumab Biosimilar MIL60; Bevacizumab Biosimilar Mvasi; Bevacizumab Biosimilar MYL-1402O; Bevacizumab Biosimilar QL 1101; Bevacizumab Biosimilar RPH-001; Bevacizumab Biosimilar SCT501; Bevacizumab Biosimilar Zirabev; Bevacizumab-awwb; Bevacizumab-bvzr; BP102; BP102 Biosimilar; HD204; Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer; Mvasi; MYL-1402O; Recombinant Humanized Anti-VEGF Monoclonal Antibody; rhuMab-VEGF; SCT501; SIBP 04; SIBP-04; SIBP04; Zirabev; QL1101; Bevacizumab Biosimilar QL1101; BAT1706; BAT 1706; BAT-1706; BAT1706 Biosimilar; Bevacizumab Biosimilar BAT1706; Bevacizumab-adcd; CT-P16; Vegzelma; Alymsys; ABP-215; ABP215; Aybintio; Bevacizumab-aybi; Bevacizumab-equi; Bevacizumab-maly; Bevacizumab-onbe; CT P16; CTP16; Equidacent; Onbevzi; Avzivi; Bevacizumab Biosimilar MB02; Bevacizumab-tnjn; FKB 238; FKB-238; FKB238; MB 02; MB-02; MB02; Oyavas; PF 06439535; PF-06439535; PF06439535
Experimental: Arm II (paclitaxel, carboplatin, temsirolimus); Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	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; JM8; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Drug: Temsirolimus; Given IV; Other Names: Torisel; CCI-779; CCI-779 Rapamycin Analog; Cell Cycle Inhibitor 779; Rapamycin Analog; Rapamycin Analog CCI-779; CCI 779; CCI779
Experimental: Arm III (ixabepilone, carboplatin, bevacizumab); Patients receive ixabepilone IV over 1 hour, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.	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; JM8; Biological: Bevacizumab; Given IV; Other Names: Avastin; ABP 215; Anti-VEGF; Anti-VEGF Humanized Monoclonal Antibody; Anti-VEGF Monoclonal Antibody SIBP04; Anti-VEGF rhuMAb; Bevacizumab awwb; Bevacizumab Biosimilar ABP 215; Bevacizumab Biosimilar BEVZ92; Bevacizumab Biosimilar BI 695502; Bevacizumab Biosimilar CBT 124; Bevacizumab Biosimilar CT-P16; Bevacizumab Biosimilar FKB238; Bevacizumab Biosimilar GB-222; Bevacizumab Biosimilar HD204; Bevacizumab Biosimilar HLX04; Bevacizumab Biosimilar IBI305; Bevacizumab Biosimilar LY01008; Bevacizumab Biosimilar MIL60; Bevacizumab Biosimilar Mvasi; Bevacizumab Biosimilar MYL-1402O; Bevacizumab Biosimilar QL 1101; Bevacizumab Biosimilar RPH-001; Bevacizumab Biosimilar SCT501; Bevacizumab Biosimilar Zirabev; Bevacizumab-awwb; Bevacizumab-bvzr; BP102; BP102 Biosimilar; HD204; Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer; Mvasi; MYL-1402O; Recombinant Humanized Anti-VEGF Monoclonal Antibody; rhuMab-VEGF; SCT501; SIBP 04; SIBP-04; SIBP04; Zirabev; QL1101; Bevacizumab Biosimilar QL1101; BAT1706; BAT 1706; BAT-1706; BAT1706 Biosimilar; Bevacizumab Biosimilar BAT1706; Bevacizumab-adcd; CT-P16; Vegzelma; Alymsys; ABP-215; ABP215; Aybintio; Bevacizumab-aybi; Bevacizumab-equi; Bevacizumab-maly; Bevacizumab-onbe; CT P16; CTP16; Equidacent; Onbevzi; Avzivi; Bevacizumab Biosimilar MB02; Bevacizumab-tnjn; FKB 238; FKB-238; FKB238; MB 02; MB-02; MB02; Oyavas; PF 06439535; PF-06439535; PF06439535; Drug: Ixabepilone; Given IV; Other Names: BMS-247550; Ixempra; (1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-8,8,10,12,16-pentamethyl-3-[(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-17-oxa-4-azabicyclo[14.1.0]heptadecane-5,9-dione; Azaepothilone B; BMS 247550; BMS247550; Epothilone; Epothilone-B BMS 247550

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Progressed or Died by 25 Months From Enrollment	PFS (Progression free survival) is defined as the duration of time from date of study entry to time of progression or death, whichever occurs first. Patients with a status of alive, progression-free are censored at their date of last follow-up. To lessen the potential for bias in the progression evaluation times between treatment arms and historical controls, progression/death times will be grouped over 6 18-week time intervals. Progressions are carried forward to the end of the interval. All progressions or deaths occurring after the 6th 18-week interval are censored at 25 months for this analysis. Study NCT00977574	at 25 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and Severity of Toxicity as Assessed by CTCAE v3.0 for Each of the Three Arms.		Median of 10 cycles of treatment plus 30 days
The Median Duration of Overall Survival for Each of the Three Arms.	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.	Time from date of study entry to time of death or the date of last contact, assessed up to 5 years
The Proportion of Patients With Measurable Disease Who Have Confirmed Objective Tumor Responses by Treatment.	RECIST 1.1 was used to define objective tumor response. A complete response is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. A partial response is defined as At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. There can be no unequivocal progression of non-target lesions and no new lesions. Complete and partial responses are included in the objective tumor response rate. Confirmation of response was not required.	Imaging was done every 3 cycles and at any other time clinically indicated. Imaging was required every 9 weeks until progression or initiation on non protocol therapy. After 2 years of protocol therapy or follow up, CT scan or MRI was every 3 months

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: NRG Oncology
• Investigators: Principal Investigator: Carol Aghajanian, NRG Oncology

Publications and helpful links

General Publications

• Thiel KW, Devor EJ, Filiaci VL, Mutch D, Moxley K, Alvarez Secord A, Tewari KS, McDonald ME, Mathews C, Cosgrove C, Dewdney S, Aghajanian C, Samuelson MI, Lankes HA, Soslow RA, Leslie KK. TP53 Sequencing and p53 Immunohistochemistry Predict Outcomes When Bevacizumab Is Added to Frontline Chemotherapy in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study. J Clin Oncol. 2022 Oct 1;40(28):3289-3300. doi: 10.1200/JCO.21.02506. Epub 2022 Jun 3.
• Leslie KK, Filiaci VL, Mallen AR, Thiel KW, Devor EJ, Moxley K, Richardson D, Mutch D, Secord AA, Tewari KS, McDonald ME, Mathews C, Cosgrove C, Dewdney S, Casablanca Y, Jackson A, Rose PG, Zhou X, McHale M, Lankes H, Levine DA, Aghajanian C. Mutated p53 portends improvement in outcomes when bevacizumab is combined with chemotherapy in advanced/recurrent endometrial cancer: An NRG Oncology study. Gynecol Oncol. 2021 Apr;161(1):113-121. doi: 10.1016/j.ygyno.2021.01.025. Epub 2021 Feb 2.

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2009
• Primary Completion (Actual): January 31, 2015
• Study Completion (Estimated): March 6, 2027

Study Registration Dates

• First Submitted: September 12, 2009
• First Submitted That Met QC Criteria: September 12, 2009
• First Posted (Estimated): September 15, 2009

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Neoplasms by Histologic Type; Uterine Diseases; Genital Diseases, Female; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Uterine Neoplasms; Sarcoma; Neoplasms, Connective and Soft Tissue; Cystadenocarcinoma; Neoplasms, Cystic, Mucinous, and Serous; Neoplasms, Complex and Mixed; Recurrence; Carcinoma; Adenocarcinoma; Endometrial Neoplasms; Cystadenocarcinoma, Serous; Carcinosarcoma; Mixed Tumor, Mullerian; Carcinoma, Adenosquamous; Adenocarcinoma, Clear Cell; Amino Acids, Peptides, and Proteins; Proteins; Sulfur Compounds; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Health Care Economics and Organizations; Macrolides; Lactones; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Hydrogen Sulfide; Polyketides; Economics; Bevacizumab; Sirolimus; Carboplatin; Paclitaxel; Immunoglobulin G; Epothilones; Disulfides; temsirolimus; ixabepilone; Taxes
• Other Study ID Numbers: NCI-2011-01969 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180868 (U.S. NIH Grant/Contract); U10CA027469 (U.S. NIH Grant/Contract); GOG-0086P (Other Identifier: CTEP); CDR0000654472