Recurrent Uterine Corpus Sarcoma, Uterine Carcinosarcoma
Conditions
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.
Interventions
DRUGIxabepilone
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
NRG Oncology
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumor Response | 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 | Proportion of participants with objective tumor response. Objective tumor response is defined as complete or partial tumor response as assessed by RECIST 1.1. |
| Adverse Events (Grade 3 or Higher) During Treatment Period. | During treatment and up to 30 days after stopping the study treatment | Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | From study entry to disease progression, death or date of last contact, whichever occurs first, up to 5 years of follow-up. | Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is assessed by RECIST 1.1 |
| Overall Survival | From study entry to death or last contact, up to 5 years of follow-up. | Overall survival is defined as the duration of time from study entry to time of death or the date of last contact. |
Countries
United States
Participant flow
Recruitment details
The study was activated on 9/7/2010 and closed to accrual on 8/26/2013 (suspended from 3/5/2012 to 9/30/2012).
Participants by arm
| Arm | Count |
|---|---|
| Ixabepilone Ixabepilone administered at 40 mg/m2 IV infusion over 3 hours on day 1 of a 21-day cycle until disease progression or adverse effects prohibit further treatment | 34 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible-Inadequate pathology | 1 |
| Overall Study | Ineligible-Second primary cancer site | 1 |
| Overall Study | Ineligible- Wrong cell type | 6 |
Baseline characteristics
| Characteristic | Ixabepilone |
|---|---|
| Age, Continuous | 66.9 years STANDARD_DEVIATION 7.7 |
| Age, Customized 20-29 years | 0 Participants |
| Age, Customized 30-39 years | 0 Participants |
| Age, Customized 40-49 years | 0 Participants |
| Age, Customized 50-59 years | 7 Participants |
| Age, Customized 60-69 years | 13 Participants |
| Age, Customized 70-79 years | 12 Participants |
| Age, Customized 80-89 years | 2 Participants |
| Histologic Type Carcinosarcoma-heterologus | 17 participants |
| Histologic Type Carcinosarcoma-homologous | 11 participants |
| Histologic Type Carcinosarcoma, MMT | 6 participants |
| International Federation of Gynecology and Obstetrics (FIGO) Stage - Recurrent/Persistent | 34 participants |
| Sex: Female, Male Female | 34 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 34 / 34 |
| serious Total, serious adverse events | 17 / 34 |
Outcome results
Primary
Adverse Events (Grade 3 or Higher) During Treatment Period.
Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0
Time frame: During treatment and up to 30 days after stopping the study treatment
Population: Eligible and Treated Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ixabepilone | Adverse Events (Grade 3 or Higher) During Treatment Period. | Leukopenia | 15 participants |
| Ixabepilone | Adverse Events (Grade 3 or Higher) During Treatment Period. | Musculoskelatal and connective tissue disorders | 1 participants |
| Ixabepilone | Adverse Events (Grade 3 or Higher) During Treatment Period. | Neoplasms benign, malignant and unspecified | 2 participants |
| Ixabepilone | Adverse Events (Grade 3 or Higher) During Treatment Period. | Peripheral sensory neuropathy | 1 participants |
| Ixabepilone | Adverse Events (Grade 3 or Higher) During Treatment Period. | Other nervous system disorders | 2 participants |
| Ixabepilone | Adverse Events (Grade 3 or Higher) During Treatment Period. | Respitory, thoracic and mediastinal disorders | 5 participants |
| Ixabepilone | Adverse Events (Grade 3 or Higher) During Treatment Period. | Vascular disorders | 8 participants |
| Ixabepilone | Adverse Events (Grade 3 or Higher) During Treatment Period. | Thrombocytopenia | 0 participants |
| Ixabepilone | Adverse Events (Grade 3 or Higher) During Treatment Period. | Neutropenia | 16 participants |
| Ixabepilone | Adverse Events (Grade 3 or Higher) During Treatment Period. | Anemia | 5 participants |
| Ixabepilone | Adverse Events (Grade 3 or Higher) During Treatment Period. | Other Investigations | 4 participants |
| Ixabepilone | Adverse Events (Grade 3 or Higher) During Treatment Period. | Other Blood/lymphatics | 2 participants |
| Ixabepilone | Adverse Events (Grade 3 or Higher) During Treatment Period. | Cardiac Disorders | 1 participants |
| Ixabepilone | Adverse Events (Grade 3 or Higher) During Treatment Period. | Gastrointestinal disorders | 6 participants |
| Ixabepilone | Adverse Events (Grade 3 or Higher) During Treatment Period. | General disorders and administration site conditio | 9 participants |
| Ixabepilone | Adverse Events (Grade 3 or Higher) During Treatment Period. | Infections and infestations | 3 participants |
| Ixabepilone | Adverse Events (Grade 3 or Higher) During Treatment Period. | Metabolism and nutrition disorders | 12 participants |
Primary
Objective Tumor Response
Proportion of participants with objective tumor response. Objective tumor response is defined as complete or partial tumor response as assessed by RECIST 1.1.
Time frame: 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
Population: Eligible and Treated Patients. Measure of dispersion is 95% One-sided confidence Interval
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ixabepilone | Objective Tumor Response | 11.8 percentage |
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.
Time frame: From study entry to death or last contact, up to 5 years of follow-up.
Population: Eligible and Treated Patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone | Overall Survival | 7.7 months |
Secondary
Progression-free Survival
Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is assessed by RECIST 1.1
Time frame: From study entry to disease progression, death or date of last contact, whichever occurs first, up to 5 years of follow-up.
Population: Eligible and Treated Patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ixabepilone | Progression-free Survival | 1.7 months |