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

Endometrial Cancer Clinical Trial

— IXAMPLE2  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00883116
• Other study ID #: CA163-196
• Secondary ID: 2008-007167-16
• Status: Terminated
• Phase: Phase 3
• First received: April 16, 2009
• Last updated: June 16, 2015
• Start date: August 2009
• Est. completion date: December 2013

Study information

• Verified date: June 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaAustralia: Department of Health and Ageing Therapeutic Goods AdministrationBelgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentBrazil: National Health Surveillance AgencyCanada: Health CanadaCzech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Greece: Ethics CommitteeHungary: National Institute of PharmacyItaly: Ministry of HealthKorea: Food and Drug AdministrationMexico: Federal Commission for Sanitary Risks ProtectionNorway: Directorate of HealthPeru: General Directorate of Pharmaceuticals, Devices, and DrugsPoland: Ministry of HealthRussia: Ministry of Health of the Russian FederationSpain: Spanish Agency of MedicinesSweden: Medical Products AgencyTaiwan: National Bureau of Controlled DrugsUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 500
• Est. completion date: December 2013
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

Drug:
• Ixabepilone

• Doxorubicin

• Paclitaxel

Locations

Country	Name	City	State
Argentina	Local Institution	La Rioja
Argentina	Local Institution	Rosario	Santa Fe
Argentina	Local Institution	Salta
Australia	Local Institution	East Bentleigh	Victoria
Australia	Local Institution	Milton	Queensland
Belgium	Local Institution	Gent
Belgium	Local Institution	Leuven
Brazil	Local Institution	Barretos	Sao Paulo
Brazil	Local Institution	Jau	Sao Paulo
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Sao Paulo
Canada	Local Institution	Calgary	Alberta
Canada	Local Institution	Fleurimont	Quebec
Canada	Local Institution	Halifax	Nova Scotia
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Surrey	British Columbia
Canada	Local Institution	Toronto	Ontario
Canada	Local Institution	Vancouver	British Columbia
Czech Republic	Local Institution	Brno
Czech Republic	Local Institution	Hradec Kralove
Denmark	Local Institution	Copenhagen
Denmark	Local Institution	Herlev
Denmark	Local Institution	Odense C
France	Local Institution	Paris
France	Local Institution	Poitiers
France	Local Institution	Saint Herblain Cedex
France	Local Institution	Villejuif Cedex
Greece	Local Institution	Athens
Hungary	Local Institution	Budapest
Hungary	Local Institution	Miskolc
Italy	Local Institution	Brescia
Italy	Local Institution	Campobasso
Italy	Local Institution	Meldola (fc)
Italy	Local Institution	Milano
Italy	Local Institution	Monza
Italy	Local Institution	Roma
Mexico	Local Institution	Df	Distrito Federal
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Mexico	Distrito Federal
Mexico	Local Institution	Mexico City	Distrito Federal
Mexico	Local Institution	Monterrey	Distrito Federal
Mexico	Local Institution	Tlalpan	Distrito Federal
Norway	Local Institution	Bergen
Norway	Local Institution	Oslo
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Russian Federation	Local Institution	Ivanovo
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Obninsk
Russian Federation	Local Institution	St Pertersburg
Russian Federation	Local Institution	St Petersburg
Spain	Local Institution	Barcelona
Spain	Local Institution	Madrid
Spain	Local Institution	Valencia
Sweden	Local Institution	Goteborg
Sweden	Local Institution	Linkoping
Sweden	Local Institution	Stockholm
Sweden	Local Institution	Umea
Sweden	Local Institution	Uppsala
United Kingdom	Local Institution	Bristol	Avon
United Kingdom	Local Institution	Glasgow	Dumfries & Galloway
United Kingdom	Local Institution	Leeds	Yorkshire
United Kingdom	Local Institution	Nottingham	Nottinghamshire
United States	Georgia Health Science University	Augusta	Georgia
United States	Blumenthal Cancer Center	Charlotte	North Carolina
United States	University Of Virginia	Charlottesville	Virginia
United States	Tennessee Gynecologic Oncology Group, Llc	Chattanooga	Tennessee
United States	Duke University Medical Center	Durham	North Carolina
United States	Rocky Mountain Gynecologic Oncology	Englewood	Colorado
United States	Cancer Centers Of The Carolinas	Greenville	South Carolina
United States	Sudarshan K. Sharma, Md	Hinsdale	Illinois
United States	Gynecologic Oncology Assoc.,Inc	Hollywood	Florida
United States	St. Vincent Hospital And Health Care Center, Inc.	Indianapolis	Indiana
United States	Saint Dominic's Gynecologic Oncology	Jackson	Mississippi
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Hematology And Oncology Specialists, Llc	Marrero	Louisiana
United States	University Of Minnesota	Minneapolis	Minnesota
United States	University Of South Alabama	Mobile	Alabama
United States	Peter E. Schwartz, Md	New Haven	Connecticut
United States	Peggy And Charles Stephenson Oklahoma Cancer Center	Oklahoma City	Oklahoma
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	Pennsylvania Oncology Hematology Associates	Philadelphia	Pennsylvania
United States	Magee-Womens Hospital Of Upmc Laboratory	Pittsburgh	Pennsylvania
United States	Women & Infants Hospital Of Ri	Providence	Rhode Island
United States	Women'S Health Specialists	Rockville	Maryland
United States	Matthew A Powell, Md	Saint Louis	Missouri
United States	Sarasota Memorial Health Care System	Sarasota	Florida
United States	Hematology Oncology, P.C.	Stamford	Connecticut
United States	H. Lee Moffitt Cancer Center	Tampa	Florida
United States	Tulsa Cancer Institute	Tulsa	Oklahoma
United States	Central Dupage Hospital Cancer Center	Warrenville	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Czech Republic,  Denmark,  France,  Greece,  Hungary,  Italy,  Mexico,  Norway,  Peru,  Russian Federation,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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)	No
Secondary	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)	Yes

External Links

•   BMS clinical trial educational resource
•   BMS Clinical Trial Information
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form