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A Phase II Evaluation of Brivanib (BMS582664), an Oral, Multitargeted Growth Factor Tyrosine Kinase Inhibitor in the Treatment of Recurrent or Persistent Endometrial Carcinoma

Phase 2
18 Years
Open (Enrolling)
Endometrial Cancer

Thank you

Trial Information

A Phase II Evaluation of Brivanib (BMS582664), an Oral, Multitargeted Growth Factor Tyrosine Kinase Inhibitor in the Treatment of Recurrent or Persistent Endometrial Carcinoma



- To assess the activity of brivanib alaninate, in terms of 6-month progression-free
survival (PFS) and objective tumor response, in patients with recurrent or persistent
endometrial carcinoma.


- To determine the duration of PFS and overall survival of these patients.

- To determine the nature and degree of toxicity of brivanib alaninate in these patients
as assessed by CTCAE v3.0.

OUTLINE: This is a multicenter study.

Patients receive oral brivanib alaninate once daily on days 1-28. Courses repeat every 28
days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and
then every 6 months for 3 years.

Inclusion Criteria


- 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

- 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

- 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


- 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

- 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

- Valvular heart disease ≥ grade 2 (per CTCAE v3.0 criteria)

- No active infection requiring antibiotics, except uncomplicated urinary tract

- 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


- 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

- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Frequency of patients with progression-free survival (PFS) for ≥ 6 months or objective tumor response

Safety Issue:


Principal Investigator

Matthew A. Powell, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Washington University Siteman Cancer Center


United States: Federal Government

Study ID:




Start Date:

August 2009

Completion Date:

Related Keywords:

  • Endometrial Cancer
  • recurrent endometrial carcinoma
  • endometrial adenocarcinoma
  • endometrial clear cell carcinoma
  • Endometrial Neoplasms
  • Sarcoma, Endometrial Stromal
  • Adenoma



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