Ixabepilone in Treating Patients With Recurrent or Persistent Uterine Cancer

Phase 2

Completed

Conditions: Recurrent Uterine Corpus Sarcoma
Uterine Carcinosarcoma

Interventions: Drug: Ixabepilone
Other: Laboratory Biomarker Analysis

Registration Number: NCT01168232

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 42

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (ixabepilone)	Ixabepilone	Patients receive ixabepilone IV over 3 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Treatment (ixabepilone)	Laboratory Biomarker Analysis	Patients receive ixabepilone IV over 3 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Adverse Events (Grade 3 or Higher) During Treatment Period.	During treatment and up to 30 days after stopping the study treatment	Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0
Objective Tumor Response	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	Proportion of participants with objective tumor response. Objective tumor response is defined as complete or partial tumor response as assessed by RECIST 1.1.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	From study entry to death or last contact, up to 5 years of follow-up.	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
Progression-free Survival	From study entry to disease progression, death or date of last contact, whichever occurs first, up to 5 years of follow-up.	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

Trial Locations

Locations (78): University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
John Muir Medical Center-Concord Campus
🇺🇸
Concord, California, United States
John Muir Medical Center-Walnut Creek
🇺🇸
Walnut Creek, California, United States
University of Colorado Hospital
🇺🇸
Aurora, Colorado, United States
Hartford Hospital
🇺🇸
Hartford, Connecticut, United States
Smilow Cancer Hospital Care Center at Saint Francis
🇺🇸
Hartford, Connecticut, United States
The Hospital of Central Connecticut
🇺🇸
New Britain, Connecticut, United States
Florida Hospital Orlando
🇺🇸
Orlando, Florida, United States
Memorial University Medical Center
🇺🇸
Savannah, Georgia, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸
Boise, Idaho, United States
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University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States