Ixabepilone in Treating Patients With Recurrent or Persistent Uterine Cancer

Study Overview
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Brief Summary
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This phase II trial is studying the side effects and how well ixabepilone works in treating patients with persistent or recurrent uterine cancer. Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells of by stopping them from dividing.

Detailed Description
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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.

Official Title
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A Phase II Evaluation of Ixabepilone (NSC #710428) in the Treatment of Recurrent or Persistent Carcinosarcoma of the Uterus

Conditions
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Recurrent Uterine Corpus Sarcoma, Uterine Carcinosarcoma

Intervention / Treatment
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* Drug: Ixabepilone
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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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

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (ixabepilone)<br>Patients receive ixabepilone IV over 3 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: Ixabepilone<br>* Given IV<br>* Other names: Ixempra;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumor Response | Proportion of participants with objective tumor response. Objective tumor response is defined as complete or partial tumor response as assessed by RECIST 1.1. | Every other cycle for first 6 months; then every 3 months thereafter until completion of study treatment; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease.1 cycle is 21 days | 
| Adverse Events (Grade 3 or Higher) During Treatment Period. | Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0 | During treatment and up to 30 days after stopping the study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is assessed by RECIST 1.1 | From study entry to disease progression, death or date of last contact, whichever occurs first, up to 5 years of follow-up. | 
| Overall Survival | Overall survival is defined as the duration of time from study entry to time of death or the date of last contact. | From study entry to death or last contact, up to 5 years of follow-up. |