Sunitinib Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer
Condition: Endometrial Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IVA Uterine Corpus Cancer AJCC v7; Stage IVB Uterine Corpus Cancer AJCC v7; Uterine Carcinosarcoma; Uterine Corpus Carcinosarcoma
MeSH terms: Carcinoma; Adenocarcinoma; Cystadenocarcinoma, Serous; Carcinoma, Endometrioid; Carcinosarcoma; Mixed Tumor, Mullerian; Recurrence
Intervention: Sunitinib Malate
Intervention description: Given PO
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well sunitinib malate works in treating patients with
      endometrial cancer that has come back after a period of improvement (recurrent) or has spread
      to other places in the body (metastatic). Sunitinib may stop the growth of tumor cells by
      blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed endometrial cancer;
             adenocarcinoma (endometrioid and serous/papillary serous) and carcinosarcoma (ie.
             malignant mixed Mullerian tumor [MMMT]) of the uterus will be investigated; patients
             with other histologies (eg. squamous cell carcinoma or leiomyosarcoma) are excluded

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as >=
             20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT)
             scan; indicator lesions must not have been previously treated with surgery,
             radiotherapy, or radiofrequency ablation

          -  Previously treated patients must have evidence of progressive disease, either
             clinically or radiographically, as assessed by the investigator

          -  Eligible patients may have received no more than one prior cytotoxic chemotherapy
             regimen for recurrent, locally-advanced, or metastatic disease; if the prior
             chemotherapy was an anthracycline, they may have received no more than 6 cycles (or
             less than 450 mg/m^2 doxorubicin); patients must have completed any previous
             chemotherapy a minimum of 4 weeks (or 6 weeks if the regimen contained carmustine
             [BCNU] or mitomycin) prior to study registration; prior investigational treatment is
             permissible (as long as such treatment completed 4 weeks prior to registration)

          -  Life expectancy of greater than 3 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60)

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count (ANC) >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Hemoglobin >= 100 g/dL

          -  Serum calcium =< 12.0 mg/dL (=< 3.0 mmol/L)

          -  Total serum bilirubin within normal institutional limits

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X
             institutional upper limit of normal

          -  Creatinine within normal institutional limits OR creatinine clearance >= 60
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

          -  Serum lipase =< 1.5 x institutional upper limit of normal

          -  Serum amylase =< 1.5 x institutional upper limit of normal

          -  Thyroid stimulating hormone (TSH)/T3/T4 within normal institutional limits

          -  Magnesium >= 0.5 mmol/L

          -  Patients must have corrected QT interval (QTc) < 500 msec

          -  The following group of patients are eligible provided they have normal baseline
             cardiac function (as determined by estimate of left ventricular ejection fraction
             [LVEF] on echocardiogram or multi-gated acquisition scan [MUGA]):

               -  Those with a history of congestive heart failure, provided they are no greater
                  than New York Heart Association (NYHA) class I and on treatment at baseline

               -  Those with prior anthracycline exposure

               -  Those who have received prior central thoracic radiation that included the heart
                  in the radiotherapy port

          -  Women of childbearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation; all women of childbearing potential must have a
             negative pregnancy test prior to receiving sunitinib; should a woman become pregnant
             or suspect she is pregnant while participating in this study, she should inform her
             treating physician immediately

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier; at
             least 4 weeks must have elapsed since any major surgery

          -  Patients may not be receiving any other investigational agents

          -  Patients who have received prior treatment with any other antiangiogenic agent (e.g.,
             bevacizumab, sorafenib, pazopanib, AZD2171, PTK787, vascular endothelial growth factor
             [VEGF] Trap, etc.) are ineligible

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to sunitinib

          -  Patients who have a history of serious ventricular arrhythmias (ventricular
             tachycardia [VT] or ventricular fibrillation [VF] equal to or greater than 3 beats in
             a row), QTc prolongation (defined as a QTc interval equal to or greater than 500 msec)
             or other significant electrocardiogram (ECG) abnormalities are excluded

          -  Patients with poorly controlled hypertension (systolic blood pressure of 140 mmHg or
             higher or diastolic blood pressure of 90 mmHg or higher) are ineligible

          -  Patients who require use of therapeutic doses of coumarin-derivative anticoagulants
             such as warfarin are excluded, although doses of up to 2 mg daily are permitted for
             prophylaxis of thrombosis; Note: Low molecular weight heparin is permitted provided
             the patient's prothrombin time (PT) international normalized ratio (INR) is =< 1.5

          -  Patients with any condition (e.g., gastrointestinal tract disease resulting in an
             inability to take oral medication or a requirement for intravenous [IV] alimentation,
             prior surgical procedures affecting absorption, or active peptic ulcer disease) that
             impairs their ability to swallow and retain sunitinib tablets are excluded

          -  Patients with any of the following conditions are excluded:

               -  Serious or non-healing wound, ulcer, or bone fracture

               -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
                  abscess within 28 days of treatment

               -  Any history of cerebrovascular accident (CVA) or transient ischemic attack within
                  12 months prior to study entry

               -  History of myocardial infarction, cardiac arrhythmia, stable/unstable angina,
                  symptomatic congestive heart failure, or coronary/peripheral artery bypass graft
                  or stenting within 12 months prior to study entry

               -  History of pulmonary embolism within the past 12 months

               -  Class III or IV heart failure as defined by the NYHA functional classification
                  system

               -  Pre-existing adrenal insufficiency (primary or secondary)

          -  The eligibility of patients taking medications that are potent inducers or inhibitors
             of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) will be determined
             following a review of their case by the Principal Investigator; every effort should be
             made to switch patients taking such agents or substances to other medications,
             particularly patients who are taking enzyme-inducing anticonvulsant agents

          -  Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid
             function in the normal range with medication are ineligible

          -  Patients with known brain metastases should be excluded

          -  Patients with uncontrolled intercurrent illness including, but not limited to, ongoing
             or active infections or psychiatric illness/social situations that would limit
             compliance with study requirements are ineligible

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with sunitinib malate

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible