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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01220609
Other study ID # NCI-2011-02656
Secondary ID NCI-2011-02656CD
Status Completed
Phase Phase 2
First received
Last updated
Start date November 2010
Est. completion date January 2016

Study information

Verified date August 2019
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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 information / eligibility

Status Completed
Enrollment 26
Est. completion date January 2016
Est. primary completion date July 2014
Accepts healthy volunteers No
Gender Female
Age group 18 Years and older
Eligibility 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

Study Design


Intervention

Drug:
Ixabepilone
Given IV
Other:
Laboratory Biomarker Analysis
Correlative studies

Locations

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

Sponsors (2)

Lead Sponsor Collaborator
National Cancer Institute (NCI) NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Tumor Response 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. Every other cycle for the first 6 months; then every 3 months thereafter; up to 5 years.
Primary 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 Progression-free Survival 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. From study entry to disease progression, death or date of last contact, whichever occurs first, up to 5 years of follow-up.
Secondary 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.
See also
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