Clinical trial NCT00883116: A Study of Ixabepilone as Second-line Therapy for Locally Advanced, Recurrent, or Metastatic Endometrial Cancer
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Endometrial Cancer
Lead sponsor: R-Pharm
Sponsor class: INDUSTRY
First posted: 2009-04-17
Enrollment: 551
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Date of randomization to date of death or last date censored to up to approximately 26 months
Secondary outcomes:
measure: Progression-free Survival
timeFrame: 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
measure: Best Overall Response Rate
timeFrame: Date of randomization and every 6 weeks to end of treatment (9 cycles, or approximately Day 189)
measure: 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
timeFrame: From Day 1 (first dose) to 30 days past last dose (up to Day 219); 9 cycles, or 189 days + 30 days
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University Of South Alabama
state: Alabama
city: Englewood
country: United States
facility: Rocky Mountain Gynecologic Oncology
state: Colorado
city: New Haven
country: United States
facility: Peter E. Schwartz, Md
state: Connecticut
city: Stamford
country: United States
facility: Hematology Oncology, P.C.
state: Connecticut
city: Hollywood
country: United States
facility: Gynecologic Oncology Assoc.,Inc
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Health Care System
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Augusta
country: United States
facility: Georgia Health Science University
state: Georgia
city: Hinsdale
country: United States
facility: Sudarshan K. Sharma, Md
state: Illinois
city: Warrenville
country: United States
facility: Central Dupage Hospital Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Hospital And Health Care Center, Inc.
state: Indiana
city: Marrero
country: United States
facility: Hematology And Oncology Specialists, Llc
state: Louisiana
city: Rockville
country: United States
facility: Women'S Health Specialists
state: Maryland
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: University Of Minnesota
state: Minnesota
city: Jackson
country: United States
facility: Saint Dominic's Gynecologic Oncology
state: Mississippi
city: Saint Louis
country: United States
facility: Matthew A Powell, Md
state: Missouri
city: Charlotte
country: United States
facility: Blumenthal Cancer Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Oklahoma City
country: United States
facility: Peggy And Charles Stephenson Oklahoma Cancer Center
state: Oklahoma
city: Tulsa
country: United States
facility: Tulsa Cancer Institute
state: Oklahoma
city: Philadelphia
country: United States
facility: Pennsylvania Oncology Hematology Associates
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital Of Upmc Laboratory
state: Pennsylvania
city: Providence
country: United States
facility: Women & Infants Hospital Of Ri
state: Rhode Island
city: Greenville
country: United States
facility: Cancer Centers Of The Carolinas
state: South Carolina
city: Chattanooga
country: United States
facility: Tennessee Gynecologic Oncology Group, Llc
state: Tennessee
city: Charlottesville
country: United States
facility: University Of Virginia
state: Virginia
city: Rosario
country: Argentina
facility: Local Institution
state: Santa Fe
city: La Rioja
country: Argentina
facility: Local Institution
city: Salta
country: Argentina
facility: Local Institution
city: Milton
country: Australia
facility: Local Institution
state: Queensland
city: East Bentleigh
country: Australia
facility: Local Institution
state: Victoria
city: Gent
country: Belgium
facility: Local Institution
city: Leuven
country: Belgium
facility: Local Institution
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Jau
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Calgary
country: Canada
facility: Local Institution
state: Alberta
city: Surrey
country: Canada
facility: Local Institution
state: British Columbia
city: Vancouver
country: Canada
facility: Local Institution
state: British Columbia
city: Halifax
country: Canada
facility: Local Institution
state: Nova Scotia
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Fleurimont
country: Canada
facility: Local Institution
state: Quebec
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Brno
country: Czech Republic
facility: Local Institution
city: Hradec Kralove
country: Czech Republic
facility: Local Institution
city: Copenhagen
country: Denmark
facility: Local Institution
city: Herlev
country: Denmark
facility: Local Institution
city: Odense C
country: Denmark
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Poitiers
country: France
facility: Local Institution
city: Saint Herblain Cedex
country: France
facility: Local Institution
city: Villejuif Cedex
country: France
facility: Local Institution
city: Athens
country: Greece
facility: Local Institution
city: Budapest
country: Hungary
facility: Local Institution
city: Miskolc
country: Hungary
facility: Local Institution
city: Brescia
country: Italy
facility: Local Institution
city: Campobasso
country: Italy
facility: Local Institution
city: Meldola (fc)
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution
city: Monza
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Df
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Mexico City
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Mexico
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Monterrey
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Tlalpan
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Bergen
country: Norway
facility: Local Institution
city: Oslo
country: Norway
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Ivanovo
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Obninsk
country: Russian Federation
facility: Local Institution
city: St Pertersburg
country: Russian Federation
facility: Local Institution
city: St Petersburg
country: Russian Federation
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Valencia
country: Spain
facility: Local Institution
city: Goteborg
country: Sweden
facility: Local Institution
city: Linkoping
country: Sweden
facility: Local Institution
city: Stockholm
country: Sweden
facility: Local Institution
city: Umea
country: Sweden
facility: Local Institution
city: Uppsala
country: Sweden
facility: Local Institution
city: Bristol
country: United Kingdom
facility: Local Institution
state: Avon
city: Glasgow
country: United Kingdom
facility: Local Institution
state: Dumfries & Galloway
city: Nottingham
country: United Kingdom
facility: Local Institution
state: Nottinghamshire
city: Leeds
country: United Kingdom
facility: Local Institution
state: Yorkshire
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.