A Study of Ixabepilone as Second-line Therapy for Locally Advanced, Recurrent, or Metastatic Endometrial Cancer
Condition: Endometrial Cancer
MeSH terms: Endometrial Neoplasms
Intervention: Ixabepilone; Doxorubicin; Paclitaxel
Intervention MeSH terms: Paclitaxel; Doxorubicin; Albumin-Bound Paclitaxel
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 551.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

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