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

Recurrent Uterine Corpus Sarcoma Clinical Trial

Official title:

A Phase II Evaluation of Ixabepilone (NSC #710428) in the Treatment of Recurrent or Persistent Leiomyosarcoma of the Uterus

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
• 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
• 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

Related Conditions & MeSH terms

• Leiomyosarcoma
• Recurrent Uterine Corpus Sarcoma
• Uterine Corpus Leiomyosarcoma

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.