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

Overview[ - collapse ][ - ]

Purpose 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.
ConditionEndometrial Cancer
InterventionDrug: Ixabepilone
Drug: Doxorubicin
Drug: Paclitaxel
PhasePhase 3
SponsorBristol-Myers Squibb
Responsible PartyBristol-Myers Squibb
ClinicalTrials.gov IdentifierNCT00883116
First ReceivedApril 16, 2009
Last UpdatedFebruary 12, 2014
Last verifiedFebruary 2014

Tracking Information[ + expand ][ + ]

First Received DateApril 16, 2009
Last Updated DateFebruary 12, 2014
Start DateAugust 2009
Estimated Primary Completion DateDecember 2013
Current Primary Outcome MeasuresOverall Survival (OS) [Time Frame: Date of randomization to date of death or last date censored to up to approximately 26 months] [Designated as safety issue: No]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.
Current Secondary Outcome Measures
  • 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] [Designated as safety issue: No]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 o1 or more measurable lesions.
  • Best Overall Response Rate [Time Frame: Date of randomization and every 6 weeks to end of treatment (9 cycles, or approximately Day 189)] [Designated as safety issue: No]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.
  • 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)] [Designated as safety issue: Yes]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.

Descriptive Information[ + expand ][ + ]

Brief TitleA Study of Ixabepilone as Second-line Therapy for Locally Advanced, Recurrent, or Metastatic Endometrial Cancer
Official TitleA 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
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.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionEndometrial Cancer
InterventionDrug: Ixabepilone
Other Names:
  • Ixempra
  • BMS-247550
Drug: Doxorubicin
Other Names:
  • Adriamycin PFS/RDF
  • Adriacin
  • Adriblastina
  • Adriablastine
  • Adrimedac
  • DOXO-CELL
  • Doxolem
  • Doxorubin
  • Farmiblastina
  • Rubex
Drug: Paclitaxel
Other Names:
  • Taxol
  • Anzatax
  • Asotax
  • Bristaxol Praxel
  • Taxol Konzentrat
  • F1-106
Study Arm (s)
  • 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
  • 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.

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment500
Estimated Completion DateDecember 2013
Estimated Primary Completion DateJune 2012
Eligibility Criteria
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
GenderFemale
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States, Argentina, Australia, Belgium, Brazil, Canada, Czech Republic, Denmark, France, Greece, Hungary, Italy, Mexico, Norway, Peru, Russian Federation, Spain, Sweden, United Kingdom

Administrative Information[ + expand ][ + ]

NCT Number NCT00883116
Other Study ID NumbersCA163-196
Has Data Monitoring CommitteeYes
Information Provided ByBristol-Myers Squibb
Study SponsorBristol-Myers Squibb
CollaboratorsNot Provided
Investigators Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Verification DateFebruary 2014

Locations[ + expand ][ + ]

University Of South Alabama
Mobile, Alabama, United States, 36604
Rocky Mountain Gynecologic Oncology
Englewood, Colorado, United States, 80113
Peter E. Schwartz, Md
New Haven, Connecticut, United States, 06510-3206
Hematology Oncology, P.C.
Stamford, Connecticut, United States, 06902
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
Georgia Health Science University
Augusta, Georgia, United States, 30912-3335
Sudarshan K. Sharma, Md
Hinsdale, Illinois, United States, 60521
Central Dupage Hospital Cancer Center
Warrenville, Illinois, United States, 60555
St. Vincent Hospital And Health Care Center, Inc.
Indianapolis, Indiana, United States, 46260
Hematology And Oncology Specialists, Llc
Marrero, Louisiana, United States, 70072
Women'S Health Specialists
Rockville, Maryland, United States, 20852
Sparrow Regional Cancer Center
Lansing, Michigan, United States, 48912
University Of Minnesota
Minneapolis, Minnesota, United States, 55455-0374
Saint Dominic's Gynecologic Oncology
Jackson, Mississippi, United States, 39216
Matthew A Powell, Md
Saint Louis, Missouri, United States, 63110
Blumenthal Cancer Center
Charlotte, North Carolina, United States, 28204
Duke University Medical Center
Durham, North Carolina, United States, 27710
Peggy And Charles Stephenson Oklahoma Cancer Center
Oklahoma City, Oklahoma, United States, 73104
Tulsa Cancer Institute
Tulsa, Oklahoma, United States, 74136
Pennsylvania Oncology Hematology Associates
Philadelphia, Pennsylvania, United States, 19106
Magee-Womens Hospital Of Upmc Laboratory
Pittsburgh, Pennsylvania, United States, 15213
Women & Infants Hospital Of Ri
Providence, Rhode Island, United States, 02908
Cancer Centers Of The Carolinas
Greenville, South Carolina, United States, 29615
Tennessee Gynecologic Oncology Group, Llc
Chattanooga, Tennessee, United States, 37403
University Of Virginia
Charlottesville, Virginia, United States, 22908
Local Institution
Rosario, Santa Fe, Argentina, S2000DSK
Local Institution
La Rioja, Argentina, 5300
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Salta, Argentina, A4406CLA
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Milton, Queensland, Australia, 4064
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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
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Calgary, Alberta, Canada, T2N 4N2
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Surrey, British Columbia, Canada, V3V 1Z2
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Vancouver, British Columbia, Canada, V5Z 4E6
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Halifax, Nova Scotia, Canada, B3H 1V7
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Toronto, Ontario, Canada, M5G 2M9
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Fleurimont, Quebec, Canada, J1H 5N4
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Montreal, Quebec, Canada, H2L 4M1
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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, Distrito Federal, Mexico, 07760
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Mexico City, Distrito Federal, Mexico, 06726
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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, LIMA 13
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Lima, Peru, Lima 11
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Lima, Peru, 34
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Ivanovo, Russian Federation, 153013
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Moscow, Russian Federation, 117997
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Moscow, Russian Federation, 115 478
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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
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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