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

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.

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