Ixabepilone in Treating Patients With Recurrent or Persistent Uterine Cancer

PRIMARY OBJECTIVES:

I. To determine the response rate of ixabepilone in patients with persistent or recurrent
carcinosarcoma of the uterus.

II. To determine the nature and degree of toxicity of ixabepilone in this cohort of patients.

SECONDARY OBJECTIVES:

I. To determine the duration of progression-free survival and overall survival.

TERTIARY OBJECTIVES:

I. To examine the expression of class III beta-tubulin in carcinosarcoma of the uterus.

II. To explore the association between class III beta-tubulin expression in carcinosarcoma of
the uterus and response, progression-free and overall survival.

OUTLINE:

Patients receive ixabepilone IV over 3 hours on day 1. Treatment repeats every 21 days in the
absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.

Inclusion Criteria:

- Patients must have histologically confirmed uterine carcinosarcoma which is persistent
or recurrent with documented disease progression after appropriate local therapy;
acceptable histologic type is defined as carcinosarcoma (malignant mixed muellerian
tumor), homologous or heterologous type

- All patients must have measurable disease; measurable disease is defined by Response
Evaluation Criteria In Solid Tumors (RECIST) (version 1.1); measurable disease is
defined as at least one lesion that can be accurately measured in at least one
dimension (longest diameter to be recorded); each lesion must be >= 10 mm when
measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper
measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes
must be >= 15 mm in short axis when measured by CT or MRI

- Patients must have at least one ?target lesion? to be used to assess response on this
protocol as defined by RECIST version 1.1; tumors within a previously irradiated field
will be designated as ?non-target? lesions unless progression is documented or a
biopsy is obtained to confirm persistence at least 90 days following completion of
radiation therapy

- Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG)
protocol, if one exists; in general, this would refer to any active GOG Phase III or
Rare Tumor protocol for the same patient population

- Patients must have a GOG Performance Status of 0, 1, or 2

- Recovery from effects of recent surgery, radiotherapy, or chemotherapy

- Patients should be free of active infection requiring antibiotics (with the
exception of uncomplicated urinary tract infection [UTI])

- Any hormonal therapy directed at the malignant tumor must be discontinued at
least one week prior to registration

- Any other prior therapy directed at the malignant tumor, including biological and
immunologic agents, must be discontinued at least three weeks prior to
registration

- Patients must have had one prior chemotherapeutic regimen for management of
carcinosarcoma; initial treatment may include chemotherapy, chemotherapy and radiation
therapy, and/or consolidation/maintenance therapy; chemotherapy administered in
conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic
chemotherapy regimen

- Patients who have NOT received prior therapy with a taxane (such as paclitaxel or
docetaxel) MUST receive a second regimen that includes a taxane

- Patients must have NOT received any additional cytotoxic chemotherapy except as noted
above

- Patients are allowed to receive, but are not required to receive, one additional
non-cytotoxic regimen for management of recurrent or persistent disease according to
the following definition:

- Non-cytotoxic (biologic or cytostatic) agents include (but are not limited to)
monoclonal antibodies, cytokines, and small-molecule inhibitors of signal
transduction

- Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl

- Platelets greater than or equal to 100,000/mcl

- Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)

- Bilirubin less than or equal to 1.5 x ULN

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) less
than or equal to 3 x ULN

- Alkaline phosphatase less than or equal to 2.5 x ULN

- Patients must have signed an approved informed consent and authorization permitting
release of personal health information

Exclusion Criteria:

- Neuropathy (sensory and motor) less than or equal to grade 1

- Patients who have met the pre-entry requirements

- Patients of childbearing potential must have a negative serum pregnancy test 72 hours
prior to the study entry and be practicing an effective form of contraception

- Patients who have received prior therapy with Ixabepilone

- Patients with a known history of severe (Common Terminology Criteria for Adverse
Events [CTCAE] version [v]4.0) grade 3 or 4 hypersensitivity reaction to agents
containing Cremophor? EL or its derivatives (eg, polyoxyethylated castor oil)

- Patients with other invasive malignancies, with the exception of non-melanoma skin
cancer, and other specific malignancies, are excluded if there is any evidence of
other malignancy being present within the last three years; patients are also excluded
if their previous cancer treatment contraindicates this protocol therapy

- Patients who have received prior radiotherapy to any portion of the abdominal cavity
or pelvis OTHER THAN for the treatment of uterine carcinosarcoma within the last three
years are excluded; prior radiation for localized cancer of the breast, head and neck,
or skin is permitted, provided that it was completed more than three years prior to
registration, and the patient remains free of recurrent or metastatic disease

- Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER
THAN for the treatment of uterine carcinosarcoma within the last three years are
excluded; patients may have received prior adjuvant chemotherapy for localized breast
cancer, provided that it was completed more than three years prior to registration,
and that the patient remains free of recurrent or metastatic disease

- Patients who are pregnant or nursing