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

NCT ID: NCT01220609

Last Updated: 2019-08-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2016-01-31

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.

Conditions

Recurrent Uterine Corpus Sarcoma; Uterine Corpus Leiomyosarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (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.

Group Type: EXPERIMENTAL

Ixabepilone

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Interventions

Ixabepilone

Given IV

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

BMS 247550; BMS-247550

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

NRG Oncology

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Linda Duska

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

Gynecologic Oncology Group of Arizona

Phoenix, Arizona, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Los Angeles County-USC Medical Center

Los Angeles, California, United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

University of Colorado Cancer Center - Anschutz Cancer Pavilion

Aurora, Colorado, United States

Hartford Hospital

Hartford, Connecticut, United States

Saint Francis Hospital and Medical Center

Hartford, Connecticut, United States

The Hospital of Central Connecticut

New Britain, Connecticut, United States

Florida Gynecologic Oncology

Fort Myers, Florida, United States

John B Amos Cancer Center

Columbus, Georgia, United States

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Sudarshan K Sharma MD Limted-Gynecologic Oncology

Hinsdale, Illinois, United States

Advocate Christ Medical Center

Oak Lawn, Illinois, United States

Cadence Cancer Center in Warrenville

Warrenville, Illinois, United States

Saint Vincent Oncology Center

Indianapolis, Indiana, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Greater Baltimore Medical Center

Baltimore, Maryland, United States

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, United States

Michigan Cancer Research Consortium Community Clinical Oncology Program

Ann Arbor, Michigan, United States

Oakwood Hospital and Medical Center

Dearborn, Michigan, United States

Henry Ford Hospital

Detroit, Michigan, United States

Saint John Hospital and Medical Center

Detroit, Michigan, United States

Hurley Medical Center

Flint, Michigan, United States

Genesys Regional Medical Center-West Flint Campus

Flint, Michigan, United States

Allegiance Health

Jackson, Michigan, United States

Borgess Medical Center

Kalamazoo, Michigan, United States

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Sparrow Hospital

Lansing, Michigan, United States

Saint Mary Mercy Hospital

Livonia, Michigan, United States

Saint Joseph Mercy Oakland

Pontiac, Michigan, United States

Saint Joseph Mercy Port Huron

Port Huron, Michigan, United States

Saint Mary's of Michigan

Saginaw, Michigan, United States

Saint John Macomb-Oakland Hospital

Warren, Michigan, United States

Singing River Hospital

Pascagoula, Mississippi, United States

Phelps County Regional Medical Center

Rolla, Missouri, United States

Saint John's Clinic-Rolla-Cancer and Hematology

Rolla, Missouri, United States

Mercy Hospital Springfield

Springfield, Missouri, United States

Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield

Springfield, Missouri, United States

CoxHealth South Hospital

Springfield, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Women's Cancer Center of Nevada

Las Vegas, Nevada, United States

Cooper Hospital University Medical Center

Camden, New Jersey, United States

Carolinas Medical Center

Charlotte, North Carolina, United States

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Summa Akron City Hospital/Cooper Cancer Center

Akron, Ohio, United States

Case Western Reserve University

Cleveland, Ohio, United States

Cleveland Clinic Cancer Center/Fairview Hospital

Cleveland, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Riverside Methodist Hospital

Columbus, Ohio, United States

Hillcrest Hospital Cancer Center

Mayfield Heights, Ohio, United States

Lake University Ireland Cancer Center

Mentor, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Tulsa Cancer Institute

Tulsa, Oklahoma, United States

Abington Memorial Hospital

Abington, Pennsylvania, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

Geisinger Medical Center-Cancer Center Hazleton

Hazleton, Pennsylvania, United States

Geisinger Medical Group

State College, Pennsylvania, United States

Geisinger Wyoming Valley

Wilkes-Barre, Pennsylvania, United States

Women and Infants Hospital

Providence, Rhode Island, United States

Greenville Health System Cancer Institute-Faris

Greenville, South Carolina, United States

Greenville Health System Cancer Institute-Eastside

Greenville, South Carolina, United States

Greenville Health System Cancer Institute-Spartanburg

Spartanburg, South Carolina, United States

Avera Cancer Institute

Sioux Falls, South Dakota, United States

University of Virginia

Charlottesville, Virginia, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

D N Greenwald Center

Mukwonago, Wisconsin, United States

Oconomowoc Memorial Hospital-ProHealth Care Inc

Oconomowoc, Wisconsin, United States

Waukesha Memorial Hospital - ProHealth Care

Waukesha, Wisconsin, United States

Countries

United States

References

Duska LR, Blessing JA, Rotmensch J, Mannel RS, Hanjani P, Rose PG, Dizon DS. A Phase II evaluation of ixabepilone (IND #59699, NSC #710428) in the treatment of recurrent or persistent leiomyosarcoma of the uterus: an NRG Oncology/Gynecologic Oncology Group Study. Gynecol Oncol. 2014 Oct;135(1):44-8. doi: 10.1016/j.ygyno.2014.07.101. Epub 2014 Aug 1.

Reference Type: DERIVED

PMID: 25091619 (View on PubMed)

Other Identifiers

NCI-2011-02656

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000686644

Identifier Type: -

Identifier Source: secondary_id

GOG-0131H

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA027469

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA180868

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02656

Identifier Type: -

Identifier Source: org_study_id