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

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

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Uterine Corpus Sarcoma; Uterine Corpus Leiomyosarcoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Ixabepilone

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Gynecologic Oncology Group of Arizona
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • Los Angeles County-USC Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center - Anschutz Cancer Pavilion
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • Hartford, Connecticut, United States, 06105
      • Saint Francis Hospital and Medical Center
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
  • Florida
    • Fort Myers, Florida, United States, 33905
      • Florida Gynecologic Oncology
  • Georgia
    • Columbus, Georgia, United States, 31904
      • John B Amos Cancer Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Hinsdale, Illinois, United States, 60521
      • Sudarshan K Sharma MD Limted-Gynecologic Oncology
    • Oak Lawn, Illinois, United States, 60453-2699
      • Advocate Christ Medical Center
    • Warrenville, Illinois, United States, 60555
      • Cadence Cancer Center in Warrenville
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Saint Vincent Oncology Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium Community Clinical Oncology Program
    • Dearborn, Michigan, United States, 48124
      • Oakwood Hospital and Medical Center
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • Flint, Michigan, United States, 48502
      • Hurley Medical Center
    • Flint, Michigan, United States, 48532
      • Genesys Regional Medical Center-West Flint Campus
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
    • Livonia, Michigan, United States, 48154
      • Saint Mary Mercy Hospital
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Saint Joseph Mercy Port Huron
    • Saginaw, Michigan, United States, 48601
      • Saint Mary's of Michigan
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
  • Mississippi
    • Pascagoula, Mississippi, United States, 39581
      • Singing River Hospital
  • Missouri
    • Rolla, Missouri, United States, 65401
      • Phelps County Regional Medical Center
    • Rolla, Missouri, United States, 65401
      • Saint John's Clinic-Rolla-Cancer and Hematology
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
    • Springfield, Missouri, United States, 65804
      • Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Women's Cancer Center of Nevada
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Akron City Hospital/Cooper Cancer Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Mentor, Ohio, United States, 44060
      • Lake University Ireland Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Tulsa, Oklahoma, United States, 74146
      • Tulsa Cancer Institute
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Hazleton, Pennsylvania, United States, 18201
      • Geisinger Medical Center-Cancer Center Hazleton
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Faris
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System Cancer Institute-Eastside
    • Spartanburg, South Carolina, United States, 29307
      • Greenville Health System Cancer Institute-Spartanburg
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Mukwonago, Wisconsin, United States, 53149
      • D N Greenwald Center
    • Oconomowoc, Wisconsin, United States, 53066-3896
      • Oconomowoc Memorial Hospital-ProHealth Care Inc
    • Waukesha, Wisconsin, United States, 53188
      • Waukesha Memorial Hospital - ProHealth Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Ixabepilone; Given IV; Other Names: BMS-247550; BMS 247550

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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

Outcome Measure	Measure Description	Time Frame
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.
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.

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: NRG Oncology
• Investigators: Principal Investigator: Linda Duska, NRG Oncology

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: October 12, 2010
• First Submitted That Met QC Criteria: October 12, 2010
• First Posted (Estimate): October 14, 2010

Study Record Updates

• Last Update Posted (Actual): August 8, 2019
• Last Update Submitted That Met QC Criteria: August 6, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Sarcoma; Neoplasms, Muscle Tissue; Recurrence; Leiomyosarcoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Epothilones
• Other Study ID Numbers: NCI-2011-02656 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180868 (U.S. NIH Grant/Contract); U10CA027469 (U.S. NIH Grant/Contract); CDR0000686644; GOG-0131H (Other Identifier: CTEP)