Brivanib Alaninate in Treating Patients With Recurrent or Persistent Endometrial Cancer

DISEASE CHARACTERISTICS:

• Histologically confirmed endometrial carcinoma, including any of the following epithelial cell types:

  • Endometrioid adenocarcinoma
  • Serous adenocarcinoma
  • Undifferentiated carcinoma
  • Clear cell adenocarcinoma
  • Mixed epithelial carcinoma
  • Adenocarcinoma not otherwise specified
  • Mucinous adenocarcinoma
  • Squamous cell carcinoma
  • Transitional cell carcinoma
• Recurrent or persistent disease that is refractory to curative therapy or established treatments
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques (e.g., palpation, plain x-ray, CT scan, or MRI) or ≥ 10 mm by spiral CT scan

• Must have ≥ 1 target lesion to assess response as defined by RECIST criteria

  • Tumors within a previously irradiated field will be designated as "non-target" lesions unless there is documented disease progression or a biopsy is obtained to confirm persistence ≥ 90 days after completion of radiotherapy
• Must not be eligible for a higher priority GOG protocol, if one exists

• Must have received 1 prior chemotherapeutic regimen for management of endometrial carcinoma

  • Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer will be counted as a systemic chemotherapy regimen
  • One additional cytotoxic regimen for management of recurrent or persistent disease allowed
• No known brain metastases

PATIENT CHARACTERISTICS:

• GOG performance status (PS) 0-2 (for patients who have received 1 prior regimen) OR GOG PS 0-1 (for patients who have received 2 prior regimens)
• ANC ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Hemoglobin > 9 g/dL

• Creatinine ≤ 1.5 times upper limit of normal (ULN)

  • Urine protein: proteinuria must be ≤ 3+ by dipstick
  • Patients with urine protein > 3+ who undergo a 24 hour urine collection and demonstrate ≤ 3.5 g in 24 h allowed
• Bilirubin ≤ 1.5 times ULN
• AST/ALT ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN
• Albumin ≥ 2.5 g/dL
• PT/INR ≤ 1.5 times ULN
• Baseline serum potassium ≥ 3.5 mmol/L (potassium supplementation allowed)
• QTc ≤ 450 msec by ECG
• LVEF > 50%
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
• No pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
• No neuropathy (sensory and motor) > grade 1 (per CTCAE v3.0 criteria)
• No hyponatremia (i.e., sodium < 130 mEq/L)
• No active/known HIV, hepatitis B, or hepatitis C
• No gastrointestinal bleeding or any other hemorrhage/bleeding event ≥ grade 3 (per CTCAE v3.0 criteria) within the past 30 days
• No poor wound healing, non-healing ulcers, or bone fractures within the past 3 months

• No uncontrolled or significant cardiovascular disease, including any of the following:

  • Myocardial infarction within the past 12 months
  • Uncontrolled angina within the past 12 months
  • NYHA class III-IV congestive heart failure
  • Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or diastolic BP > 100 mm Hg, despite optimized antihypertensive therapy
  • History of stroke, transient ischemic attack, or other CNS ischemic event
  • Cardiac arrhythmias requiring antiarrhythmic therapy, except beta blockers or digoxin
  • Valvular heart disease ≥ grade 2 (per CTCAE v3.0 criteria)
• No active infection requiring antibiotics, except uncomplicated urinary tract infection
• No inability to swallow tablets or untreated malabsorption syndrome
• No serious uncontrolled medical disorder or active infection that would impair the ability of the patient to receive study therapy or whose control may be jeopardized by the complications of this therapy
• No other invasive malignancies within the past 3 years, except nonmelanoma skin cancer or other specific malignancies

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior surgery, radiotherapy, or chemotherapy
• At least 1 week since prior hormonal therapy directed at the malignant tumor
• At least 3 weeks since prior immunologic agents or other therapy directed at the malignant tumor
• No prior non-cytotoxic therapy for management of endometrial carcinoma, except hormonal therapy
• No prior brivanib alaninate or other anti-vascular, anti-PDGFR, or anti-FGFR therapy

• No prior radiotherapy to any portion of the abdominal cavity or pelvis, except for the treatment of endometrial carcinoma within the past 5 years

  • Prior radiotherapy for localized cancer of the breast, head and neck, or skin allowed provided it was completed > 3 years ago and the patient remains free of recurrent or metastatic disease

• No prior chemotherapy for any abdominal or pelvic tumor, except for the treatment of endometrial carcinoma within the past 5 years

  • Prior adjuvant chemotherapy for localized breast cancer allowed provided it was completed > 3 years ago and the patient remains free of recurrent or metastatic disease
• No prior cancer treatment that would contraindicate study therapy
• No concurrent chronic antiplatelet therapy (e.g., aspirin > 300 mg/day or clopidogrel ≥ 75 mg/day)

• No concurrent warfarin for prophylaxis or treatment of thrombosis allowed

  • Low-molecular weight heparin allowed
• Concurrent low molecular weight heparin allowed provided PT/INR ≤ 1.5