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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Endometrial Cancer

Intervention / Treatment
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* Drug: Ixabepilone
* Drug: Doxorubicin
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ixabepilone, 40 mg/m^2, intravenously (IV)<br>Participants received ixabepilone, 40 mg/m^2, given IV over 3 hours every 21 days until unacceptable toxicity or disease progression | Drug: Ixabepilone<br> <br> * Other names: BMS-247550;|
| Active Comparator: Control chemotherapy (Paclitaxel or Doxorubicin)<br>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<br> <br> * Other names: Rubex;Drug: Paclitaxel<br> <br> * Other names: F1-106;|

What is the study measuring?
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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 |