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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01220609
First received: October 12, 2010
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Recurrent Uterine Sarcoma
Uterine Leiomyosarcoma
Other: diagnostic laboratory biomarker analysis
Drug: ixabepilone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Evaluation of Ixabepilone (NSC #710428) in the Treatment of Recurrent or Persistent Leiomyosarcoma of the Uterus

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Frequency and duration of objective response (complete or partial response) as measured by RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Frequency and severity of adverse events as assessed by NCI CTCAE v. 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 51
Study Start Date: November 2010
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: diagnostic laboratory biomarker analysis
Correlative studies
Drug: ixabepilone
Given IV
Other Names:
  • BMS-247550
  • epothilone B lactam
  • Ixempra

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: This is a multicenter study.

Patients receive ixabepilone IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Tumor tissue samples from prior surgery may be collected for beta-III tubulin expression analysis by IHC.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01220609

  Show 72 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Linda Duska Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01220609     History of Changes
Other Study ID Numbers: NCI-2011-02656, NCI-2011-02656, CDR0000686644, GOG-0131H, GOG-0131H, GOG-0131H, U10CA027469
Study First Received: October 12, 2010
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leiomyosarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neoplasms, Muscle Tissue
Sarcoma
Epothilones
Antimitotic Agents
Antineoplastic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 25, 2014