Please note that the ANZCTR website will be unavailable from 1pm until 2pm (AEST) on Wednesday 29th May for website maintenance. Please be sure to log out of the system in order to avoid any loss of data. Thank you and apologies for any inconvenience caused.

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00883116




Registration number
NCT00883116
Ethics application status
Date submitted
16/04/2009
Date registered
16/04/2009
Date last updated
27/01/2017

Titles & IDs
Public title
A Study of Ixabepilone as Second-line Therapy for Locally Advanced, Recurrent, or Metastatic Endometrial Cancer
Scientific 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
Secondary ID [1] 0 0
2008-007167-16
Secondary ID [2] 0 0
CA163-196
Universal Trial Number (UTN)
Trial acronym
IXAMPLE2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endometrial Cancer 0 0
Endometrial Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ixabepilone
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Ixabepilone
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Paclitaxel

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.

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.


Treatment: Drugs: Ixabepilone


Treatment: Drugs: Doxorubicin


Treatment: Drugs: Paclitaxel


Treatment: Drugs: Ixabepilone


Treatment: Drugs: Doxorubicin


Treatment: Drugs: Paclitaxel


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Date of randomization to date of death or last date censored to up to approximately 26 months
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
Date of randomization to date of death or last date censored to up to approximately 26 months
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Date of randomization and every 6 weeks to end of treatment (9 cycles, or approximately Day 189)
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
From Day 1 (first dose) to 30 days past last dose (up to Day 219); 9 cycles, or 189 days + 30 days
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Date of randomization and every 6 weeks to end of treatment (9 cycles, or approximately Day 189)
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
From Day 1 (first dose) to 30 days past last dose (up to Day 219); 9 cycles, or 189 days + 30 days

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Local Institution - Milton
Recruitment hospital [2] 0 0
Local Institution - East Bentleigh
Recruitment postcode(s) [1] 0 0
4064 - Milton
Recruitment postcode(s) [2] 0 0
3165 - East Bentleigh
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Mississippi
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Oklahoma
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
Rhode Island
Country [18] 0 0
United States of America
State/province [18] 0 0
South Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
Argentina
State/province [21] 0 0
Santa Fe
Country [22] 0 0
Argentina
State/province [22] 0 0
La Rioja
Country [23] 0 0
Argentina
State/province [23] 0 0
Salta
Country [24] 0 0
Belgium
State/province [24] 0 0
Gent
Country [25] 0 0
Belgium
State/province [25] 0 0
Leuven
Country [26] 0 0
Brazil
State/province [26] 0 0
Rio Grande Do Sul
Country [27] 0 0
Brazil
State/province [27] 0 0
Sao Paulo
Country [28] 0 0
Canada
State/province [28] 0 0
Alberta
Country [29] 0 0
Canada
State/province [29] 0 0
British Columbia
Country [30] 0 0
Canada
State/province [30] 0 0
Nova Scotia
Country [31] 0 0
Canada
State/province [31] 0 0
Ontario
Country [32] 0 0
Canada
State/province [32] 0 0
Quebec
Country [33] 0 0
Czech Republic
State/province [33] 0 0
Brno
Country [34] 0 0
Czech Republic
State/province [34] 0 0
Hradec Kralove
Country [35] 0 0
Denmark
State/province [35] 0 0
Copenhagen
Country [36] 0 0
Denmark
State/province [36] 0 0
Herlev
Country [37] 0 0
Denmark
State/province [37] 0 0
Odense C
Country [38] 0 0
France
State/province [38] 0 0
Paris
Country [39] 0 0
France
State/province [39] 0 0
Poitiers
Country [40] 0 0
France
State/province [40] 0 0
Saint Herblain Cedex
Country [41] 0 0
France
State/province [41] 0 0
Villejuif Cedex
Country [42] 0 0
Greece
State/province [42] 0 0
Athens
Country [43] 0 0
Hungary
State/province [43] 0 0
Budapest
Country [44] 0 0
Hungary
State/province [44] 0 0
Miskolc
Country [45] 0 0
Italy
State/province [45] 0 0
Brescia
Country [46] 0 0
Italy
State/province [46] 0 0
Campobasso
Country [47] 0 0
Italy
State/province [47] 0 0
Meldola (fc)
Country [48] 0 0
Italy
State/province [48] 0 0
Milano
Country [49] 0 0
Italy
State/province [49] 0 0
Monza
Country [50] 0 0
Italy
State/province [50] 0 0
Roma
Country [51] 0 0
Mexico
State/province [51] 0 0
Distrito Federal
Country [52] 0 0
Mexico
State/province [52] 0 0
Jalisco
Country [53] 0 0
Norway
State/province [53] 0 0
Bergen
Country [54] 0 0
Norway
State/province [54] 0 0
Oslo
Country [55] 0 0
Peru
State/province [55] 0 0
Lima
Country [56] 0 0
Russian Federation
State/province [56] 0 0
Ivanovo
Country [57] 0 0
Russian Federation
State/province [57] 0 0
Moscow
Country [58] 0 0
Russian Federation
State/province [58] 0 0
Obninsk
Country [59] 0 0
Russian Federation
State/province [59] 0 0
St Pertersburg
Country [60] 0 0
Russian Federation
State/province [60] 0 0
St Petersburg
Country [61] 0 0
Spain
State/province [61] 0 0
Barcelona
Country [62] 0 0
Spain
State/province [62] 0 0
Madrid
Country [63] 0 0
Spain
State/province [63] 0 0
Valencia
Country [64] 0 0
Sweden
State/province [64] 0 0
Goteborg
Country [65] 0 0
Sweden
State/province [65] 0 0
Linkoping
Country [66] 0 0
Sweden
State/province [66] 0 0
Stockholm
Country [67] 0 0
Sweden
State/province [67] 0 0
Umea
Country [68] 0 0
Sweden
State/province [68] 0 0
Uppsala
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Avon
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Dumfries & Galloway
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Nottinghamshire
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Yorkshire

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
R-Pharm
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00883116
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT00883116