Brivanib Alaninate in Treating Patients With Recurrent or Persistent Endometrial Cancer
Condition: Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma
MeSH terms: Carcinoma; Adenocarcinoma; Carcinoma, Transitional Cell; Cystadenocarcinoma, Serous; Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Cystadenocarcinoma; Recurrence
Intervention: Brivanib Alaninate; Laboratory Biomarker Analysis
Intervention description: Given PO; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well brivanib alaninate works in treating patients with
      endometrial cancer that has come back (recurred) or is persistent. Brivanib alaninate 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 recurrent or persistent endometrial carcinoma, which is refractory
             to curative therapy or established treatments; histologic confirmation of the original
             primary tumor is required

               -  Patients with the following histologic epithelial cell types are eligible:
                  endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma,
                  clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not
                  otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell, and
                  transitional cell carcinoma

          -  All patients must have measurable disease; measurable disease is defined as at least
             one lesion that can be accurately measured in at least one dimension (longest
             dimension to be recorded); each lesion must be >= 20 mm when measured by conventional
             techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic
             resonance imaging (MRI), or >= 10 mm when measured by spiral CT

          -  Patients must have at least one ?target lesion? to be used to assess response on this
             protocol as defined by Response Evaluation Criteria in Solid Tumors (RECIST); 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 who have received one prior regimen must have a GOG performance status of 0,
             1, or 2; patients who have received two prior regimens must have a GOG performance
             status of 0 or 1

          -  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 immunologic agents,
             must be discontinued at least three weeks prior to registration

          -  Patients must have had one 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

          -  Patients are allowed to receive, but are not required to receive, one additional
             cytotoxic regimen for management of recurrent or persistent endometrial 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
                  endometrial disease, as defined above; however, patients are encouraged to enroll
                  on second-line non-cytotoxic studies prior to receiving additional cytotoxic
                  therapy

          -  Patients must NOT have received any non-cytotoxic therapy for management of
             endometrial cancer with the exception of hormonal therapy

          -  Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl, equivalent to
             Common Terminology Criteria (CTCAE v3.0) grade 1

          -  Platelets greater than or equal to 100,000/mcl

          -  Hemoglobin > 9 g/dl

          -  Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), CTCAE
             v3.0 grade 1

          -  Urinalysis needs to be assessed at baseline and proteinuria must be less than or equal
             to 3+ by dipstick (CTCAE v3.0 grade 2 or less); if the urine dipstick is > 3+, a
             24-hour protein level can be done, as clinically indicated by the investigator; the
             24-hour protein level must be less than or equal to 3.5 g/24 hours (CTCAE v3.0 grade 2
             or less)

          -  Bilirubin less than or equal to 1.5 x ULN (CTCAE v3.0 grade 1)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) less
             than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)

          -  Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)

          -  Albumin greater than or equal to 2.5 g/dl

          -  Neuropathy (sensory and motor) less than or equal to CTCAE v3.0 grade 1

          -  Prothrombin time (PT) such that international normalized ratio (INR) is < 1.5 x ULN;
             patients on therapeutic warfarin are excluded from trial, anticoagulation with low
             molecular weight heparin is allowed

          -  Patients must have signed an approved informed consent and authorization permitting
             release of personal health information

          -  Patients must meet pre-entry requirements

          -  Patients of childbearing potential must have a negative serum pregnancy test performed
             48 hours prior to study entry and be practicing an effective form of contraception
             during the study and for at least 3 months after receiving the final treatment of
             brivanib

          -  All patients must have a baseline electrocardiogram completed prior to study entry;
             baseline electrocardiogram (ECG) should be repeated if corrected QT interval (QTc) is
             found to be > 450 msec; QTc must NOT be > 450 msec on both ECGs performed during the
             same visit

        Exclusion Criteria:

          -  Patients who have had prior therapy with brivanib or anti-vascular, anti-PDGFR
             (platelet-derived growth factor receptor) or anti-FGFR (fibroblast growth factor
             receptor) therapy

          -  Patients with a history of other invasive malignancies, with the exception of
             non-melanoma skin cancer and other specific malignancies as noted below, are excluded
             if there is any evidence of the 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 endometrial cancer 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 endometrial cancer 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 that are on required chronic anti-platelet therapy (aspirin > 300 mg/day, or
             clopidogrel greater than or equal to 75 mg/day)

          -  Patients with gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE
             grade >= 3 within 30 days prior to study entry

          -  Patients with a history of poor wound healing, non healing ulcers or bone fractures
             within the last 3 months

          -  Patients with uncontrolled or significant cardiovascular disease including:

               -  Myocardial infarction within 12 months

               -  Uncontrolled angina within 12 months

               -  Class III-IV New York Heart Association (NYHA) congestive heart failure

               -  Uncontrolled hypertension (systolic blood pressure [BP] > 150 or diastolic BP >
                  100 mmHg for 24 hours) despite optimized anti-hypertensive therapy; BP must be
                  below 150/100 mmHg at screening; subjects with a history of hypertension who are
                  receiving treatment with calcium channel blockers that are cytochrome P450 family
                  3, subfamily A, polypeptide 4 (CYP3A4) inhibitors should be changed to an
                  alternative antihypertensive medication before study entry

               -  History of stroke, transient ischemic attack (TIA), or other central nervous
                  system (CNS) ischemic event

               -  Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or
                  digoxin

               -  Patients must have pre-therapy left ventricle ejection fraction (LVEF) testing
                  and have an ejection fraction > 50%

               -  Patients with valvular heart disease >= CTCAE grade2

          -  Patients with a serious uncontrolled medical disorder or active infection which would
             impair the ability of the subject to receive protocol therapy or whose control may be
             jeopardized by the complications of this therapy

          -  Pre-existing thyroid abnormality with thyroid function that can not be maintained in
             the normal range with medication

          -  Patients with hyponatremia (sodium < 130 mEq/L)

          -  Patients with active/known human immunodeficiency virus (HIV), hepatitis B, or
             hepatitis C

          -  Patients with known brain metastases

          -  Patients who are pregnant or nursing

          -  Patients with inability to swallow tablets or untreated malabsorption syndrome

          -  Baseline serum potassium < 3.5 mmol/L (potassium supplementation may be given to
             restore the serum potassium above this level prior to entry study)

          -  Patients on therapeutic warfarin anticoagulation will be excluded; patients converted
             to anticoagulation with a heparin compound will be allowed provided the patient?s PT
             is such that international normalized ratio (INR) is =< 1.5 x ULN