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

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

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.

Study Overview

• Status: Terminated
• Conditions: Endometrial Cancer
• Intervention / Treatment: Drug: Doxorubicin; Drug: Ixabepilone; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 551
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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: BMS-247550; Ixempra
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: Adriacin; Adriblastina; Adrimedac; DOXO-CELL; Doxolem; Doxorubin; Farmiblastina; Rubex; Adriamycin PFS/RDF; Adriablastine; Drug: Paclitaxel; Other Names: Taxol; Anzatax; Asotax; Taxol Konzentrat; Bristaxol Praxel; F1-106

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	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.	Date of randomization to date of death or last date censored to up to approximately 26 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	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.	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
Best Overall Response Rate	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.	Date of randomization and every 6 weeks to end of treatment (9 cycles, or approximately Day 189)
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	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.	From Day 1 (first dose) to 30 days past last dose (up to Day 219); 9 cycles, or 189 days + 30 days

Collaborators and Investigators

• Sponsor: R-Pharm

Publications and helpful links

General Publications

• McMeekin S, Dizon D, Barter J, Scambia G, Manzyuk L, Lisyanskaya A, Oaknin A, Ringuette S, Mukhopadhyay P, Rosenberg J, Vergote I. Phase III randomized trial of second-line ixabepilone versus paclitaxel or doxorubicin in women with advanced endometrial cancer. Gynecol Oncol. 2015 Jul;138(1):18-23. doi: 10.1016/j.ygyno.2015.04.026. Epub 2015 Apr 26.

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: April 16, 2009
• First Submitted That Met QC Criteria: April 16, 2009
• First Posted (Estimate): April 17, 2009

Study Record Updates

• Last Update Posted (Actual): March 9, 2017
• Last Update Submitted That Met QC Criteria: January 27, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Paclitaxel; Albumin-Bound Paclitaxel; Doxorubicin
• Other Study ID Numbers: CA163-196; 2008-007167-16