A Study of Ixabepilone as Second-line Therapy for Locally Advanced, Recurrent, or Metastatic Endometrial Cancer (IXAMPLE2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00883116
Recruitment Status : Terminated (Interim analysis results showed that ixabepilone did not improve survival compared with control chemotherapies.)
First Posted : April 17, 2009
Results First Posted : March 14, 2014
Last Update Posted : March 9, 2017
Information provided by (Responsible Party):

Brief Summary:
The primary purpose of this study is to investigate whether administration of ixabepilone results in superior outcome as assessed by overall survival compared with that achieved with standard chemotherapy (paclitaxel or doxorubicin) in women with advanced endometrial cancer that has progressed following first-line chemotherapy.

Condition or disease Intervention/treatment Phase
Endometrial Cancer Drug: Ixabepilone Drug: Doxorubicin Drug: Paclitaxel Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 551 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Open Label, Randomized, 2 Arm Study of Ixabepilone Administered Every 21 Days Versus Paclitaxel or Doxorubicin Administered Every 21 Days in Women With Advanced Endometrial Cancer Who Have Previously Been Treated With Chemotherapy
Study Start Date : August 2009
Actual Primary Completion Date : June 2012
Actual Study Completion Date : February 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Ixabepilone, 40 mg/m^2, intravenously (IV)
Participants received ixabepilone, 40 mg/m^2, given IV over 3 hours every 21 days until unacceptable toxicity or disease progression
Drug: Ixabepilone
Other Names:
  • Ixempra
  • BMS-247550

Active Comparator: Control chemotherapy (Paclitaxel or Doxorubicin)
Participants received either paclitaxel, 175 mg/m^2 given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity or doxorubicin, 60 mg/m^2 given IV per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m^2.
Drug: Doxorubicin
Other Names:
  • Adriamycin PFS/RDF
  • Adriacin
  • Adriblastina
  • Adriablastine
  • Adrimedac
  • Doxolem
  • Doxorubin
  • Farmiblastina
  • Rubex

Drug: Paclitaxel
Other Names:
  • Taxol
  • Anzatax
  • Asotax
  • Bristaxol Praxel
  • Taxol Konzentrat
  • F1-106

Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Date of randomization to date of death or last date censored to up to approximately 26 months ]
    Survival was defined as the time from the date of randomization until the date of death. If the patient did not die, OS was censored on the last date he or she was known to be alive.

Secondary Outcome Measures :
  1. Progression-free Survival [ Time Frame: Date of randomization to date of disease progression or death (or date of last tumor assessment for those who did not die or progress) up to approximately 22 months ]
    Progression-free survival was defined as the time from randomization to the date of documented disease progression. Patients who died without a reported prior progression were considered to have progressed on the date of their death. Those who did not progress or die were censored on the date of their last tumor assessment. Participants who did not have any on-study tumor assessments were censored on the date they were randomized. Measurable disease was present if the patient had 1 or more measurable lesions.

  2. Best Overall Response Rate [ Time Frame: Date of randomization and every 6 weeks to end of treatment (9 cycles, or approximately Day 189) ]
    Best overall response rate was defined as the number of participants whose best response was either partial response (PR) or complete response (CR) divided by the number of participants in the treatment group. Overall tumor response was based on an integration of the evaluation of target, nontarget, and new lesions. CR=Disappearance of all clinical and radiologic evidence of target lesions. PR=At least 30% reduction in the sum of diameters of all target lesions; taking as reference the baseline study measurement. Changes in tumor measurements need not be confirmed by repeat measurements performed after the criteria for response were first met.

  3. Number of Participants With a Serious Adverse Event (SAE), an SAE Related to Study Drug, Death as Outcome, a Peripheral Neuropathy Adverse Event (AE), a Grade 3 or Higher AE, and an AE Related to Study Drug [ Time Frame: From Day 1 (first dose) to 30 days past last dose (up to Day 219); 9 cycles, or 189 days + 30 days ]
    AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related to study drug=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Key Inclusion Criteria

  • Women aged 18 years and older
  • Histologic or cytologic diagnosis of endometrial carcinoma
  • Evidence that the cancer is advanced, recurrent, or metastatic and not curable by local measures, such as surgery or radiation.
  • Karnofsky performance status >=70
  • Measurable or nonmeasurable disease that has progressed since last treatment.

    • If only disease is confined to a solitary lesion, its neoplastic nature must be confirmed by histology or cytology.
    • Disease in a previously irradiated field is acceptable as the only site of measurable disease only if there has been clear progression since completion of radiotherapy.
  • All therapy directed at endometrial cancer must be discontinued 21 days prior to start of treatment, except for hormonal therapy which must be discontinued at least 1 week prior to start of study treatment. Concurrent administration of hormone replacement therapy is allowed.
  • Prior therapy: Participants must have failed 1 prior platinum-based chemotherapeutic regimen for endometrial cancer. May have received 2 prior chemotherapy regimens if 1 regimen was given for stage I or II disease. May have received any number of prior non-cytotoxic regimens such as monoclonal antibodies, cytokines, signal transduction inhibitors, or hormonal therapy. Previous radiation therapy is allowed.

Key Exclusion Criteria

  • Carcinosarcoma (malignant mixed mullerian tumor)
  • Endometrial leiomyosarcoma and endometrial stromal sarcomas
  • Participants who received no prior chemotherapy for endometrial cancer or ≥2 prior chemotherapy regimens (exceptions defined in protocol)
  • Known brain metastases
  • Receipt of prior ixabepilone therapy
  • Concurrent active infection requiring antibiotics or other therapy
  • Concurrent unstable disease or other debilitating illness, such as congestive heart failure, unstable angina, myocardial infarction, or other cardiac disease that could jeopardize participation, within the last 6 months
  • For participants whose prior therapy did not include an anthracycline and therefore may be randomized to doxorubicin, left ventricular ejection fraction <50% as measured by multigated radionuclide angiography or echocardiography
  • History of malignancy, except nonmelanoma skin cancer, carcinoma in situ of the cervix, or carcinoma in situ of the breast, within the last 5 years that has not been treated with chemotherapy
  • Known human immunodeficiency viral infection
  • Psychiatric disorders or other conditions rendering the participant incapable of complying with protocol requirements
  • Absolute neutrophil count <1500/mm^3
  • Platelets <100,000/mm^3
  • Hemoglobin <9 g/dL
  • Total bilirubin >1.5*upper limit of normal (ULN), except for those with Gilbert's disease
  • Aspartate aminotransferase or alanine aminotransferase >2.5*ULN
  • Serum creatinine >1.5*ULN
  • Grade ≥2 neuropathy (sensory or motor)
  • No concurrent therapy (chemotherapy, hormonal, or investigational) directed at endometrial cancer during the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00883116

  Hide Study Locations
United States, Alabama
University Of South Alabama
Mobile, Alabama, United States, 36604
United States, Colorado
Rocky Mountain Gynecologic Oncology
Englewood, Colorado, United States, 80113
United States, Connecticut
Peter E. Schwartz, Md
New Haven, Connecticut, United States, 06510-3206
Hematology Oncology, P.C.
Stamford, Connecticut, United States, 06902
United States, Florida
Gynecologic Oncology Assoc.,Inc
Hollywood, Florida, United States, 33021
Florida Hospital Cancer Institute
Orlando, Florida, United States, 32804
Sarasota Memorial Health Care System
Sarasota, Florida, United States, 34239
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Georgia Health Science University
Augusta, Georgia, United States, 30912-3335
United States, Illinois
Sudarshan K. Sharma, Md
Hinsdale, Illinois, United States, 60521
Central Dupage Hospital Cancer Center
Warrenville, Illinois, United States, 60555
United States, Indiana
St. Vincent Hospital And Health Care Center, Inc.
Indianapolis, Indiana, United States, 46260
United States, Louisiana
Hematology And Oncology Specialists, Llc
Marrero, Louisiana, United States, 70072
United States, Maryland
Women'S Health Specialists
Rockville, Maryland, United States, 20852
United States, Michigan
Sparrow Regional Cancer Center
Lansing, Michigan, United States, 48912
United States, Minnesota
University Of Minnesota
Minneapolis, Minnesota, United States, 55455-0374
United States, Mississippi
Saint Dominic's Gynecologic Oncology
Jackson, Mississippi, United States, 39216
United States, Missouri
Matthew A Powell, Md
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Blumenthal Cancer Center
Charlotte, North Carolina, United States, 28204
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Oklahoma
Peggy And Charles Stephenson Oklahoma Cancer Center
Oklahoma City, Oklahoma, United States, 73104
Tulsa Cancer Institute
Tulsa, Oklahoma, United States, 74136
United States, Pennsylvania
Pennsylvania Oncology Hematology Associates
Philadelphia, Pennsylvania, United States, 19106
Magee-Womens Hospital Of Upmc Laboratory
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Women & Infants Hospital Of Ri
Providence, Rhode Island, United States, 02908
United States, South Carolina
Cancer Centers Of The Carolinas
Greenville, South Carolina, United States, 29615
United States, Tennessee
Tennessee Gynecologic Oncology Group, Llc
Chattanooga, Tennessee, United States, 37403
United States, Virginia
University Of Virginia
Charlottesville, Virginia, United States, 22908
Local Institution
Rosario, Santa Fe, Argentina, S2000DSK
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La Rioja, Argentina, 5300
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Salta, Argentina, A4406CLA
Australia, Queensland
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Milton, Queensland, Australia, 4064
Australia, Victoria
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East Bentleigh, Victoria, Australia, 3165
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Gent, Belgium, 9000
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Leuven, Belgium, B-3000
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Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
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Barretos, Sao Paulo, Brazil, 14784-400
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Jau, Sao Paulo, Brazil, 17210-120
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Sao Paulo, Brazil, 01246-000
Canada, Alberta
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Calgary, Alberta, Canada, T2N 4N2
Canada, British Columbia
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Surrey, British Columbia, Canada, V3V 1Z2
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Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Nova Scotia
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Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
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Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
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Fleurimont, Quebec, Canada, J1H 5N4
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Montreal, Quebec, Canada, H2L 4M1
Czech Republic
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Brno, Czech Republic, 656 53
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Hradec Kralove, Czech Republic, 500 05
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Copenhagen, Denmark, 2100
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Herlev, Denmark, 2730
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Odense C, Denmark, 5000
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Paris, France, 75004
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Poitiers, France, 86000
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Saint Herblain Cedex, France, 44805
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Villejuif Cedex, France, 94800
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Athens, Greece, 11528
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Budapest, Hungary, 1122
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Miskolc, Hungary, H-3526
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Brescia, Italy, 25123
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Campobasso, Italy, 86100
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Meldola (fc), Italy, 47014
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Milano, Italy, 20141
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Monza, Italy, 20052
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Roma, Italy, 00168
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Df, Distrito Federal, Mexico, 06720
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Mexico City, Distrito Federal, Mexico, 06726
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Mexico, Distrito Federal, Mexico, 07760
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Monterrey, Distrito Federal, Mexico, 64320
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Tlalpan, Distrito Federal, Mexico, 14080
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Guadalajara, Jalisco, Mexico, 44340
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Bergen, Norway, 5021
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Oslo, Norway, 0310
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Lima, Peru, 34
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Lima, Peru, Lima 11
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Lima, Peru, LIMA 13
Russian Federation
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Ivanovo, Russian Federation, 153013
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Moscow, Russian Federation, 115 478
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Moscow, Russian Federation, 117997
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Obninsk, Russian Federation, 249036
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St Pertersburg, Russian Federation, 198255
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St Petersburg, Russian Federation, 197758
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Barcelona, Spain, 08035
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Madrid, Spain, 28040
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Valencia, Spain, 46009
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Goteborg, Sweden, 413 45
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Linkoping, Sweden, 581 85
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Stockholm, Sweden, 171 76
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Umea, Sweden, 901 85
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Uppsala, Sweden, 751 85
United Kingdom
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Bristol, Avon, United Kingdom, BS2 8ED
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Glasgow, Dumfries & Galloway, United Kingdom, G12 0YN
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Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
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Leeds, Yorkshire, United Kingdom, LS9 7TF
Sponsors and Collaborators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: R-Pharm Identifier: NCT00883116     History of Changes
Other Study ID Numbers: CA163-196
First Posted: April 17, 2009    Key Record Dates
Results First Posted: March 14, 2014
Last Update Posted: March 9, 2017
Last Verified: January 2017

Additional relevant MeSH terms:
Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Liposomal doxorubicin
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors