Bevacizumab in Treating Patients With Recurrent or Persistent Endometrial Cancer

PRIMARY OBJECTIVES:

I. Assess the activity of bevacizumab, in terms of 6-month progression-free survival rate and
objective tumor response, in patients with recurrent or persistent endometrial cancer.

II. Determine the nature and degree of toxicity of bevacizumab in these patients.

SECONDARY OBJECTIVES:

I. Determine the duration of progression-free survival and overall survival of these
patients.

II. Determine the effects of prognostic factors, including performance status and
histological grade.

OUTLINE:

Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks
in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Inclusion Criteria:

- Recurrent or persistent endometrial carcinoma with histologic confirmation of the
original primary tumor

- Refractory to curative therapy or established treatments

- Measurable disease

- At least one non previously irradiated lesion that can be accurately measured in
≥ 1 dimension as ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

- Previously irradiated lesion allowed provided disease progression is
documented or a biopsy obtained to confirm persistent disease ≥ 90 days
after completion of prior radiotherapy

- Must have received 1 prior chemotherapy regimen for endometrial carcinoma

- May include high-dose therapy, consolidation, or extended therapy after surgical
or nonsurgical assessment

- Not eligible for a higher priority GOG protocol, if one exists

- No tumor involving major vessels

- No prior history or evidence of CNS disease, including primary brain tumor, seizures
not controlled with standard medical therapy, or any brain metastases

- GOG performance status (PS) 0-2 (if received 1 prior treatment regimen)

- GOG PS 0-1 (if received 2 prior treatment regimens)

- Absolute neutrophil count ≥ 1,000/mm³

- Platelet count ≥ 100,000/mm³

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

- Serum bilirubin ≤ 1.5 times ULN

- SGOT and alkaline phosphatase ≤ 2.5 times ULN

- Urine protein:creatinine ratio < 1.0

- INR < 1.5 (or in-range, usually between 2 and 3, if the patient is on a stable dose of
therapeutic warfarin)

- PTT < 1.5 times ULN

- No active infection requiring antibiotics

- No other invasive malignancy within the past 5 years except nonmelanoma skin cancer

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 6 months after
completion of study therapy

- No serious nonhealing wound or ulcer, including any of the following:

- History of abdominal fistula

- Gastrointestinal perforation

- Intra-abdominal abscess within the past 28 days

- No serious nonhealing bone fracture

- No active bleeding or pathologic conditions that carry high risk of bleeding,
including known bleeding disorder or coagulopathy

- No clinically significant cardiovascular disease, including any of the following:

- Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg or
diastolic BP > 90 mm Hg

- Myocardial infarction or unstable angina within the past 6 months

- New York Heart Association class II-IV congestive heart failure

- Serious cardiac arrhythmia requiring medication

- Ejection fraction < 50% and received prior anthracycline (including doxorubicin
and/or doxorubicin HCl liposomal)

- Grade 2 or greater peripheral vascular disease

- History of cerebrovascular accident, transient ischemic attack, or subarachnoid
hemorrhage within the past 6 months

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human or humanized antibodies

- No significant traumatic injury within the past 28 days

- See Disease Characteristics

- Recovered from recent surgery, radiotherapy, or chemotherapy

- Hormonal therapy directed at the malignant tumor must be discontinued ≥ 1 week prior
to registration

- Any other prior therapy directed at the malignant tumor, including immunologic agents,
must be discontinued ≥ 3 weeks prior to registration

- No prior chemotherapy or radiotherapy to any portion of the abdominal cavity or pelvis

- Prior chemotherapy or radiotherapy for localized cancer of the breast, head and
neck, or skin for which the patient remains free of recurrent or metastatic
disease is allowed provided it was completed ≥ 3 years prior to study

- No prior cancer treatment that contraindicates study therapy

- No prior bevacizumab or other vascular endothelial growth factor (VEGF)
pathway-targeted therapy

- One additional prior cytotoxic regimen for recurrent or persistent endometrial cancer
allowed, including 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

- No prior noncytotoxic chemotherapy for recurrent or persistent disease

- More than 28 days since major surgical procedure or open biopsy

- More than 7 days since minor surgical procedures, fine needle aspirates, or core
biopsies

- No concurrent major surgical procedure

- No concurrent prophylactic filgrastim (G-CSF) or thrombopoietic agents

- No concurrent amifostine or other protective reagents