Ixabepilone in Treating Patients With Recurrent or Persistent Leiomyosarcoma of the Uterus Previously Treated With Chemotherapy

Phase 2

Completed

Conditions: Recurrent Uterine Corpus Sarcoma
Uterine Corpus Leiomyosarcoma

Interventions: Drug: Ixabepilone
Other: Laboratory Biomarker Analysis

Registration Number: NCT01220609

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 recurrent or persistent leiomyosarcoma of the uterus previously treated with chemotherapy. Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Detailed Description: PRIMARY OBJECTIVES:

I. To determine the response rate (complete and partial responses by RECIST 1.1) of ixabepilone in patients with recurrent or persistent leiomyosarcoma of the uterus who have failed one previous chemotherapy regimen.

II. To determine the nature and degree of toxicity of ixabepilone as assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4 in this cohort of patients.

SECONDARY OBJECTIVES:

I. To determine the duration of progression-free survival (PFS) and overall survival (OS).

II. To determine the level of beta-III tubulin expression measured by IHC in women with leiomyosarcoma.

III. To determine if beta-III tubulin expression as measured by IHC predicts response to ixabepilone in women with leiomyosarcoma.

OUTLINE:

Patients receive ixabepilone intravenously (IV) over 3 hours on day 1. Courses repeat 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: 26

Inclusion Criteria

Histologically confirmed uterine leiomyosarcoma
- Persistent or recurrent disease that is refractory to curative or established treatments
- Histologic confirmation of the original primary tumor is required
Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded)
- Each lesion must be ≥ 10 mm by CT scan, MRI, or caliper measurement by clinical exam OR ≥ 20 mm by chest x-ray
- Lymph nodes must be ≥ 15 mm in short axis by CT scan or MRI
Must have ≥ 1 "target lesion" to assess response
- 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 ≥ 90 days following completion of radiotherapy
Not eligible for a higher priority GOG protocol, if one exists
Must have had 1 prior cytotoxic regimen that included a taxane regimen for management of leiomyosarcoma
- Single-agent or multi-agent therapy allowed
- Patients who did not receive prior therapy with a taxane (e.g., docetaxel) must receive a second regimen that includes a taxane
No known brain metastases
GOG performance status 0-2
Life expectancy > 6 months
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Creatinine ≤ 1.5 times upper limit of normal (ULN)
Bilirubin ≤ 1.5 times ULN
AST ≤ 3 times ULN
Alkaline phosphatase ≤ 2.5 times ULN
Peripheral neuropathy (sensory or mother) ≤ grade 1
Negative pregnancy test
Not pregnant or nursing
Fertile patients must use effective contraception prior to and for the duration of study participation
Free of active infection requiring antibiotics
- Uncomplicated urinary tract infection allowed
No other invasive malignancy except non-melanoma skin cancer or curatively treated localized cancer of the breast, head and neck, or skin that was completed more than 3 years ago and the patient remains free of recurrence or metastatic disease
No history of a severe hypersensitivity reaction to agents containing Cremophor EL or its derivatives (e.g., polyoxyethylated castor oil)
No uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina
- Cardiac arrhythmia
- Psychiatric illness and/or social situations that would limit compliance with study requirements
No concurrent amifostine or other protective agents
Recovered from effects of recent surgery, radiotherapy, or chemotherapy
At least 1 week since prior hormonal therapy
- Hormonal therapy (cytotoxic or non-cytotoxic) not counted as prior regimen
At least 3 weeks since any other prior therapy directed to the malignant tumor, including immunologic agents
At least 4 weeks since prior radiation therapy
One prior non-cytotoxic (biologic or cytostatic) regimen, administered as part of the previous cytotoxic regimen or in addition to it, allowed
- Non-cytotoxic agents include, but are not limited to, the following:
  - Monoclonal antibodies
  - Cytokines
  - Small-molecule inhibitors of signal transduction
More than 3 years since radiotherapy for localized cancer of the breast, head and neck, or skin provided patient remains free of recurrence or metastatic disease
No prior ixabepilone
No prior chemotherapy for any abdominal or pelvic tumor other than for the treatment of uterine leiomyosarcoma within the past 3 years
Prior chemotherapy for localized breast cancer allowed provided it was completed more than 3 years ago and patient remains free of recurrent or metastatic disease
No other concurrent investigational agents
No concurrent strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine, voriconazole, or grapefruit juice) or CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifampicin, rifabutin, phenobarbital, or St. John wort)
No concurrent combination antiretroviral therapy for HIV-positive patients

Exclusion Criteria

Not provided

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. Courses repeat 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. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Tumor Response	Every other cycle for the first 6 months; then every 3 months thereafter; up to 5 years.	Complete and Partial Tumor Response by RECIST 1.1. RECIST 1.1 defines complete response as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm and the disappearance of all non-target lesions and normalization of tumor marker level. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. 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.
Frequency and Severity of Adverse Events as Assessed by NCI CTCAE v. 4.0	Every cycle until completion of study treatment up to 30 days after stopping study treatment

Secondary Outcome Measures

Name	Time	Method
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 (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression was based on RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.
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.

Trial Locations

Locations (72): John B Amos Cancer Center
🇺🇸
Columbus, Georgia, United States
Sudarshan K Sharma MD Limted-Gynecologic Oncology
🇺🇸
Hinsdale, Illinois, United States
Hillcrest Hospital Cancer Center
🇺🇸
Mayfield Heights, Ohio, United States
Geisinger Medical Center-Cancer Center Hazleton
🇺🇸
Hazleton, Pennsylvania, United States
Greenville Health System Cancer Institute-Faris
🇺🇸
Greenville, South Carolina, United States
Saint Joseph Mercy Oakland
🇺🇸
Pontiac, Michigan, United States
Tulsa Cancer Institute
🇺🇸
Tulsa, Oklahoma, United States
Singing River Hospital
🇺🇸
Pascagoula, Mississippi, United States
Carolinas Medical Center
🇺🇸
Charlotte, North Carolina, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Novant Health Presbyterian Medical Center
🇺🇸
Charlotte, North Carolina, United States
Saint John Macomb-Oakland Hospital
🇺🇸
Warren, Michigan, United States
Saint Joseph Mercy Port Huron
🇺🇸
Port Huron, Michigan, United States
Cooper Hospital University Medical Center
🇺🇸
Camden, New Jersey, United States
Avera Cancer Institute
🇺🇸
Sioux Falls, South Dakota, United States
Saint Mary's of Michigan
🇺🇸
Saginaw, Michigan, United States
Abington Memorial Hospital
🇺🇸
Abington, Pennsylvania, United States
Mercy Hospital Springfield
🇺🇸
Springfield, Missouri, United States
Summa Akron City Hospital/Cooper Cancer Center
🇺🇸
Akron, Ohio, United States
University of Virginia
🇺🇸
Charlottesville, Virginia, United States
Women and Infants Hospital
🇺🇸
Providence, Rhode Island, United States
Greenville Health System Cancer Institute-Spartanburg
🇺🇸
Spartanburg, South Carolina, United States
Greenville Health System Cancer Institute-Eastside
🇺🇸
Greenville, South Carolina, United States
University of Chicago Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Advocate Christ Medical Center
🇺🇸
Oak Lawn, Illinois, United States
Case Western Reserve University
🇺🇸
Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Geisinger Medical Group
🇺🇸
State College, Pennsylvania, United States
Greater Baltimore Medical Center
🇺🇸
Baltimore, Maryland, United States
Phelps County Regional Medical Center
🇺🇸
Rolla, Missouri, United States
Saint John's Clinic-Rolla-Cancer and Hematology
🇺🇸
Rolla, Missouri, United States
Cleveland Clinic Cancer Center/Fairview Hospital
🇺🇸
Cleveland, Ohio, United States
Riverside Methodist Hospital
🇺🇸
Columbus, Ohio, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Geisinger Wyoming Valley
🇺🇸
Wilkes-Barre, Pennsylvania, United States
Waukesha Memorial Hospital - ProHealth Care
🇺🇸
Waukesha, Wisconsin, United States
The Hospital of Central Connecticut
🇺🇸
New Britain, Connecticut, United States
Los Angeles County-USC Medical Center
🇺🇸
Los Angeles, California, United States
Women's Cancer Center of Nevada
🇺🇸
Las Vegas, Nevada, United States
Gynecologic Oncology Group of Arizona
🇺🇸
Phoenix, Arizona, United States
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
Saint John Hospital and Medical Center
🇺🇸
Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
CoxHealth South Hospital
🇺🇸
Springfield, Missouri, United States
USC / Norris Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Saint Francis Hospital and Medical Center
🇺🇸
Hartford, Connecticut, United States
Hartford Hospital
🇺🇸
Hartford, Connecticut, United States
Florida Gynecologic Oncology
🇺🇸
Fort Myers, Florida, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸
Boise, Idaho, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
Saint Vincent Oncology Center
🇺🇸
Indianapolis, Indiana, United States
Cadence Cancer Center in Warrenville
🇺🇸
Warrenville, Illinois, United States
University of Iowa Hospitals and Clinics
🇺🇸
Iowa City, Iowa, United States
Allegiance Health
🇺🇸
Jackson, Michigan, United States
Oakwood Hospital and Medical Center
🇺🇸
Dearborn, Michigan, United States
Bronson Methodist Hospital
🇺🇸
Kalamazoo, Michigan, United States
Sparrow Hospital
🇺🇸
Lansing, Michigan, United States
Hurley Medical Center
🇺🇸
Flint, Michigan, United States
Saint Mary Mercy Hospital
🇺🇸
Livonia, Michigan, United States
West Michigan Cancer Center
🇺🇸
Kalamazoo, Michigan, United States
Lake University Ireland Cancer Center
🇺🇸
Mentor, Ohio, United States
Oconomowoc Memorial Hospital-ProHealth Care Inc
🇺🇸
Oconomowoc, Wisconsin, United States
Borgess Medical Center
🇺🇸
Kalamazoo, Michigan, United States
Genesys Regional Medical Center-West Flint Campus
🇺🇸
Flint, Michigan, United States
D N Greenwald Center
🇺🇸
Mukwonago, Wisconsin, United States
Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield
🇺🇸
Springfield, Missouri, United States
Michigan Cancer Research Consortium Community Clinical Oncology Program
🇺🇸
Ann Arbor, Michigan, United States
University of Wisconsin Hospital and Clinics
🇺🇸
Madison, Wisconsin, United States
Saint Joseph Mercy Hospital
🇺🇸
Ann Arbor, Michigan, United States
Nebraska Methodist Hospital
🇺🇸
Omaha, Nebraska, United States
University of Colorado Cancer Center - Anschutz Cancer Pavilion
🇺🇸
Aurora, Colorado, United States