Ixabepilone in Treating Patients With Recurrent or Persistent Endometrial Cancer

Study Overview
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Brief Summary
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Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop tumor cells from dividing so they stop growing or die. This phase II trial is studying how well ixabepilone works in treating patients with recurrent or persistent endometrial cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the response rate in patients with recurrent or persistent endometrial adenocarcinoma treated with ixabepilone. II. Determine the nature and degree of toxicity of this drug in these patients. OUTLINE: This is a multicenter study. Patients receive ixabepilone IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 19-51 patients will be accrued for this study within 2.5 years.

Official Title
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A Phase II Evaluation of Ixabepilone (BMS-247550) [NCI-Supplied Agent, NSC #710428]) in the Treatment of Recurrent or Persistent Endometrial Carcinoma

Conditions
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Endometrial Adenocarcinoma, Recurrent Endometrial Carcinoma, Stage IV Endometrial Carcinoma

Intervention / Treatment
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* Drug: ixabepilone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed endometrial adenocarcinoma Recurrent or persistent disease Histologic confirmation of the original primary tumor is required Not amenable to management with any of the following: Surgery Radiotherapy Higher priority or standard chemotherapy Measurable disease At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques (e.g., palpation, plain x-ray, CT scan, or MRI) OR ≥ 10 mm by spiral CT scan At least 1 target lesion Tumors within a previously irradiated field are designated as non-target lesions Disease in an irradiated field as the only site of measurable disease is acceptable as a target lesion only if there has been clear progression of the lesion at least 90 days after completion of radiotherapy Received 1, and only 1, prior chemotherapy regimen (e.g., high-dose therapy, consolidation, or extended therapy administered after surgery or non-surgical assessment) for management of endometrial adenocarcinoma Ineligible for a higher priority Gynecologic Oncology Group (GOG) protocol (e.g., any active GOG phase III study for the same patient population) Performance status - GOG 0-2 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST (aspartate aminotransferase) ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN Creatinine ≤ 1.5 times ULN Sensory or motor neuropathy ≤ grade 1 Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active infection requiring antibiotics No other invasive malignancies within the past 5 years except non-melanoma skin cancer At least 3 weeks since prior biologic or immunologic agents directed at the malignant tumor One prior non-cytotoxic* (biologic or cytostatic) regimen for management of recurrent or persistent disease allowed See Disease Characteristics Prior paclitaxel or docetaxel allowed Recovered from prior chemotherapy No more than 1 prior cytotoxic chemotherapy regimen (either single or combination drug therapy) No prior ixabepilone At least 1 week since prior hormonal therapy directed at the malignant tumor Continuation of hormone replacement therapy allowed See Disease Characteristics Recovered from prior radiotherapy Recovered from prior surgery At least 3 weeks since other prior therapy directed at the malignant tumor No prior cancer treatment that contraindicates study therapy
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. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: ixabepilone<br>* Given IV<br>* Other names: Ixempra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response | RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate. | Every other cycle for first 6 months; then every six 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 | 
| Frequency and Severity of Observed Adverse Effects Associated With Protocol Therapy (CTCAE Version 3) |  | Every cycle until completion of study treatment up to 30 days after stopping study treatment (average length of data collection = 4 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. | 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. |