Pazopanib Hydrochloride in Treating Patients With Recurrent or Persistent Uterine Cancer

Inclusion Criteria:

* Patients must have histologically confirmed uterine carcinosarcoma which is persistent or recurrent; acceptable histological type is defined as carcinosarcoma (malignant mixed müllerian tumor), homologous or heterologous type
* 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 greater than or equal to 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI), or caliper measurement by clinical exam or greater than or equal to 20 mm when measured by chest x-ray
  * Lymph nodes must be greater than or equal to 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 protocol 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 (chemotherapy) directed at the malignant tumor, must be discontinued at least three weeks prior to registration
  * At least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: hysterectomy, resection of a lung nodule - minor: central venous access catheter placement)
* 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 are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease according to the following definition:

  * Cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa
  * Note: patients on this non-cytotoxic study are allowed to receive one additional cytotoxic chemotherapy regimen for management of recurrent or persistent disease, as defined above; however, due to the novel nature of biologic compounds, patients are encouraged to enroll on second-line non-cytotoxic studies prior to receiving additional cytotoxic therapy
  * Patients must have NOT received any non-cytotoxic chemotherapy for management of recurrent or persistent disease; prior hormonal therapy is permitted
* Absolute neutrophil count (ANC) greater than or equal to 1,500/mcL
* Platelets greater than or equal to 100,000/mcL
* Hemoglobin level greater than or equal to 9 g/dL
* Creatinine less than or equal to 1.5 x institutional upper limit of normal (ULN)
* Urine protein/creatinine ratio (UPCR) must be less than 1 (or urinary protein less than 1.0 g/24 hours)
* Bilirubin less than or equal to 1.5 x ULN (subjects with Gilbert syndrome and elevations of indirect bilirubin only are eligible)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x ULN
* Alkaline phosphatase less than or equal to 2.5 x ULN
* Subjects who have BOTH bilirubin greater than ULN and AST/ALT greater than ULN are not eligible

  * Specifically, if bilirubin is greater than 1 x ULN but less than or equal to 1.5 x ULN, THEN the AST and ALT must be less than or equal to ULN for patient to be eligible; if AST and/or ALT are greater than 1 x ULN but less than or equal to 2.5 x ULN, THEN the bilirubin must be less than or equal to ULN for patient to be eligible
* Prothrombin time (PT) such that international normalized ratio (INR) is less than or equal to 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) less than or equal to 1.5 x ULN
* Patients with a history of hypothyroidism/hyperthyroidism must have had stable well-controlled thyroid function for a minimum of 2 months as a condition for eligibility and that all other patients must have normal baseline thyroid function tests (thyroid stimulating hormone \[TSH\], triiodothyronine \[T\]3, T4)
* Patients must have the ability to understand and sign an approved informed consent and authorization permitting release of personal health information
* Patients who have met the pre-entry requirements
* Patients must be capable of taking and absorbing oral medications; a patient must be clear of the following:

  * Any lesion, whether induced by tumor, radiation or other conditions, which makes it difficult to swallow tablets
  * Prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel
  * Active peptic ulcer disease
  * Malabsorption syndrome
* Patients must be capable of taking and absorbing oral medications
* A patient must be clear of the following:

  * Any lesion, whether induced by tumor, radiation, or other conditions, which makes it difficult to swallow tablets
  * Prior surgical procedures affecting absorption including, but not limited to, major resection of stomach or small bowel
  * Active peptic ulcer disease
  * Malabsorption syndrome
* Any concomitant medications that are associated with a risk of corrected QC (QTc) prolongation and/or Torsades de pointes should be discontinued or replaced with drugs that do not carry these risks, if possible; patients who must take medication with a risk of possible risk of Torsades de pointes should be watched carefully for symptoms of QTc prolongation, such as syncope

  * Patients with personal or family history of congenital long QTc syndrome are NOT eligible
* Strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are prohibited; grapefruit juice is also an inhibitor of CYP450 and should not be taken with pazopanib; CYP3A4 Inducers: strong inducers of CYP3A4 are prohibited; cytochrome P450 (CYP) substrates: concomitant use of agents with narrow therapeutic windows that are metabolized by CYP3A4, cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6), or cytochrome P450, family 2, subfamily C, poly peptide 8 (CYP2C8) is not recommended
* Patients of childbearing potential must have a negative pregnancy test prior to the study treatment and agree to be practicing an effective form of contraception throughout study treatment; pregnant women are excluded from this study

Exclusion Criteria:

* Patients who have had prior therapy with pazopanib
* Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, 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 with clinically significant cardiovascular disease; this includes:

  * Patients must have blood pressure (BP) no greater than 140 mmHg (systolic) and 90 mmHg (diastolic) for eligibility
  * Myocardial infarction or unstable angina within 6 months of the first date of pazopanib therapy
  * New York Heart Association (NYHA) class II or greater congestive heart failure
  * History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications; this does not include asymptomatic, atrial fibrillation with controlled ventricular rate
  * Women who have received prior anthracycline (e.g., doxorubicin and/or liposomal doxorubicin) and who have an ejection fraction less than the institutional lower limit of normal will be excluded from the study; patients with a prior life time exposure to doxorubicin (or liposomal doxorubicin) of greater than 300 mg/m\^2 are NOT eligible
  * CTCAE grade 2 or greater peripheral vascular disease
  * History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of pazopanib therapy
  * Women with a baseline QTc \>= 480 milliseconds
  * History of cardiac angioplasty or stenting within 6 months prior to registration; history of coronary artery bypass graft surgery within 6 months prior to registration
  * A patient with arterial thrombosis within 6 months prior to enrollment
* Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy or any brain metastases
* Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
* Patients with serious, non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to the first date of pazopanib therapy; patients with underlying lesions that caused the fistula or perforation in the past that have not been corrected
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib
* Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible
* Patients who are nursing; patients who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug
* Patients with any condition that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation, including:

  * Active peptic ulcer disease
  * Known gastrointestinal intraluminal metastatic lesions (gastrointestinal serosa metastatic lesion are permitted)
  * Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease)
* History of hemoptysis in excess of 2.5 mL (1/2 teaspoon) within 8 weeks prior to first dose of pazopanib
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements