Clinical trial NCT01168232: Ixabepilone in Treating Patients With Recurrent or Persistent Uterine Cancer
Official title: A Phase II Evaluation of Ixabepilone (NSC #710428) in the Treatment of Recurrent or Persistent Carcinosarcoma of the Uterus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Uterine Corpus Sarcoma
Uterine Carcinosarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: NRG Oncology
First posted: 2010-07-23
Enrollment: 42
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial is studying the side effects and how well ixabepilone works in treating patients with persistent or recurrent uterine cancer. Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells of by stopping them from dividing.

Detailed description: PRIMARY OBJECTIVES:

I. To determine the response rate of ixabepilone in patients with persistent or recurrent carcinosarcoma of the uterus.

II. To determine the nature and degree of toxicity of ixabepilone in this cohort of patients.

SECONDARY OBJECTIVES:

I. To determine the duration of progression-free survival and overall survival.

TERTIARY OBJECTIVES:

I. To examine the expression of class III beta-tubulin in carcinosarcoma of the uterus.

II. To explore the association between class III beta-tubulin expression in carcinosarcoma of the uterus and response, progression-free and overall survival.

OUTLINE:

Patients receive ixabepilone IV over 3 hours on day 1. Treatment repeats 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.

Eligibility criteria: Inclusion Criteria:

* Patients must have histologically confirmed uterine carcinosarcoma which is persistent or recurrent with documented disease progression after appropriate local therapy; acceptable histologic type is defined as carcinosarcoma (malignant mixed muellerian tumor), homologous or heterologous type
* All patients must have measurable disease; measurable disease is defined by Response Evaluation Criteria In Solid Tumors (RECIST) (version 1.1); measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be \>= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or \>= 20 mm when measured by chest x-ray; lymph nodes must be \>= 15 mm in short axis when measured by CT or MRI
* Patients must have at least one ?target lesion? to be used to assess response on this protocol as defined by RECIST version 1.1; 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 at least 90 days following completion of radiation therapy
* Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG Phase III or Rare Tumor protocol for the same patient population
* Patients must have a GOG Performance Status of 0, 1, or 2
* Recovery from effects of recent surgery, radiotherapy, or chemotherapy

  * Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection \[UTI\])
  * Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration
  * Any other prior therapy directed at the malignant tumor, including biological and immunologic agents, must be discontinued at least three weeks prior to registration
* Patients must have had one prior chemotherapeutic regimen for management of carcinosarcoma; initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen
* Patients who have NOT received prior therapy with a taxane (such as paclitaxel or docetaxel) MUST receive a second regimen that includes a taxane
* Patients must have NOT received any additional cytotoxic chemotherapy except as noted above
* Patients are allowed to receive, but are not required to receive, one additional non-cytotoxic regimen for management of recurrent or persistent disease according to the following definition:

  * Non-cytotoxic (biologic or cytostatic) agents include (but are not limited to) monoclonal antibodies, cytokines, and small-molecule inhibitors of signal transduction
* Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl
* Platelets greater than or equal to 100,000/mcl
* Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)
* Bilirubin less than or equal to 1.5 x ULN
* Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) less than or equal to 3 x ULN
* Alkaline phosphatase less than or equal to 2.5 x ULN
* Patients must have signed an approved informed consent and authorization permitting release of personal health information

Exclusion Criteria:

* Neuropathy (sensory and motor) less than or equal to grade 1
* Patients who have met the pre-entry requirements
* Patients of childbearing potential must have a negative serum pregnancy test 72 hours prior to the study entry and be practicing an effective form of contraception
* Patients who have received prior therapy with Ixabepilone
* Patients with a known history of severe (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]4.0) grade 3 or 4 hypersensitivity reaction to agents containing Cremophor? EL or its derivatives (eg, polyoxyethylated castor oil)
* Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, and other specific malignancies, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
* Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of uterine carcinosarcoma within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
* Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of uterine carcinosarcoma within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
* Patients who are pregnant or nursing

Primary outcomes:
measure: Objective Tumor Response
timeFrame: Every other cycle for first 6 months; then every 3 months thereafter until completion of study treatment; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease.1 cycle is 21 days
measure: Adverse Events (Grade 3 or Higher) During Treatment Period.
timeFrame: During treatment and up to 30 days after stopping the study treatment
Secondary outcomes:
measure: Progression-free Survival
timeFrame: From study entry to disease progression, death or date of last contact, whichever occurs first, up to 5 years of follow-up.
measure: Overall Survival
timeFrame: From study entry to death or last contact, up to 5 years of follow-up.
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Concord
country: United States
facility: John Muir Medical Center-Concord Campus
state: California
city: Walnut Creek
country: United States
facility: John Muir Medical Center-Walnut Creek
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Hartford
country: United States
facility: Smilow Cancer Hospital Care Center at Saint Francis
state: Connecticut
city: New Britain
country: United States
facility: The Hospital of Central Connecticut
state: Connecticut
city: Orlando
country: United States
facility: Florida Hospital Orlando
state: Florida
city: Savannah
country: United States
facility: Memorial University Medical Center
state: Georgia
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center-Boise
state: Idaho
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Hinsdale
country: United States
facility: Sudarshan K Sharma MD Limted-Gynecologic Oncology
state: Illinois
city: Mount Vernon
country: United States
facility: Good Samaritan Regional Health Center
state: Illinois
city: Warrenville
country: United States
facility: Northwestern Medicine Cancer Center Warrenville
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University/Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Saint Vincent Hospital and Health Care Center
state: Indiana
city: Clive
country: United States
facility: Medical Oncology and Hematology Associates-West Des Moines
state: Iowa
city: Clive
country: United States
facility: Mercy Cancer Center-West Lakes
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Iowa-Wide Oncology Research Coalition NCORP
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates-Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates-Laurel
state: Iowa
city: Des Moines
country: United States
facility: Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Iowa Lutheran Hospital
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa/Holden Comprehensive Cancer Center
state: Iowa
city: West Des Moines
country: United States
facility: Methodist West Hospital
state: Iowa
city: West Des Moines
country: United States
facility: Mercy Medical Center-West Lakes
state: Iowa
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Ann Arbor
country: United States
facility: Michigan Cancer Research Consortium NCORP
state: Michigan
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Hospital
state: Michigan
city: Dearborn
country: United States
facility: Beaumont Hospital-Dearborn
state: Michigan
city: Detroit
country: United States
facility: Saint John Hospital and Medical Center
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Flint
country: United States
facility: Genesys Regional Medical Center-West Flint Campus
state: Michigan
city: Grand Blanc
country: United States
facility: Genesys Regional Medical Center
state: Michigan
city: Jackson
country: United States
facility: Allegiance Health
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Lansing
country: United States
facility: Sparrow Hospital
state: Michigan
city: Livonia
country: United States
facility: Saint Mary Mercy Hospital
state: Michigan
city: Pontiac
country: United States
facility: Saint Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Lake Huron Medical Center
state: Michigan
city: Saginaw
country: United States
facility: Saint Mary's of Michigan
state: Michigan
city: Warren
country: United States
facility: Saint John Macomb-Oakland Hospital
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Joplin
country: United States
facility: Mercy Hospital Joplin
state: Missouri
city: Rolla
country: United States
facility: Mercy Clinic-Rolla-Cancer and Hematology
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis Cancer and Breast Institute-South City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Springfield
country: United States
facility: Cancer Research for the Ozarks NCORP
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Springfield
country: United States
facility: CoxHealth South Hospital
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Las Vegas
country: United States
facility: Women's Cancer Center of Nevada
state: Nevada
city: Camden
country: United States
facility: Cooper Hospital University Medical Center
state: New Jersey
city: Brooklyn
country: United States
facility: State University of New York Downstate Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center/Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Akron
country: United States
facility: Summa Akron City Hospital/Cooper Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Cancer Center/Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Mayfield Heights
country: United States
facility: Hillcrest Hospital Cancer Center
state: Ohio
city: Mentor
country: United States
facility: Lake University Ireland Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists and Research Institute-Tulsa
state: Oklahoma
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
city: La Crosse
country: United States
facility: Gundersen Lutheran Medical Center
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: NRG Oncology
name: Carolyn McCourt
role: PRINCIPAL_INVESTIGATOR
References: