VEGF Trap in Treating Patients With Recurrent or Persistent Endometrial Cancer

PRIMARY OBJECTIVES:

I. Assess the activity of VEGF Trap in patients with recurrent or persistent endometrial
cancer, in terms of the frequency of patients who have progression-free survival for at least
6 months after initiating therapy or have objective tumor response.

II. Determine the toxicity of this drug in these patients.

SECONDARY OBJECTIVES:

I. Determine the duration of progression-free survival and overall survival of patients
treated with this drug.

OUTLINE:

Patients receive VEGF Trap IV over 1 hour on days 1 and 15. Treatment repeats 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, meeting both of the following
criteria:

- Recurrent or persistent disease

- Refractory to curative therapy or established treatments

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques OR ≥ 10 mm by spiral CT scan

- Tumors within a previously irradiated field are designated as nontarget lesions
unless progression is documented or a biopsy is obtained to confirm persistence
at least 90 days after completion of radiotherapy

- Must have received one prior chemotherapeutic regimen for management of endometrial
carcinoma (initial treatment may include high-dose therapy, consolidation therapy, or
extended therapy administered after surgical or non-surgical assessment)

- Not a candidate for a higher priority GOG protocol

- No history or evidence of primary brain tumor or brain metastases

- GOG performance status (PS) 0-2 (patients who received 1 prior regimen) OR GOG PS 0-1
(patients who received 2 prior regimens)

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Urine protein:creatinine ratio < 1.0 OR urine protein < 1.0 g by 24-hour urine
collection

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

- Bilirubin ≤ 1.5 times ULN

- SGOT ≤ 2.5 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN

- PT/PTT/INR ≤ 1.5 times ULN

- In-range INR (between 2 and 3) allowed if patient is on a stable dose of
therapeutic warfarin

- QTc < 500 msec

- No evidence of serious ventricular arrhythmia

- Ventricular tachycardia or ventricular fibrillation must be < 3 beats in a row

- LVEF normal

- Ejection fraction ≥ 50% (for patients who received prior anthracycline, including
doxorubicin hydrochloride and/or doxorubicin hydrochloride liposome)

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

- Uncontrolled hypertension, defined as systolic blood pressure (BP) > 140 mm Hg or
diastolic BP > 90 mm Hg

- Myocardial infarction or unstable angina within the past 6 months

- NYHA class II-IV congestive heart failure

- Serious cardiac arrhythmia requiring medication

- Peripheral vascular disease ≥ grade 2

- Cerebrovascular accident (i.e., CVA or stroke), transient ischemic attack, or
subarachnoid hemorrhage within the past 6 months

- Not pregnant or nursing

- Negative pregnancy test

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

- No HIV positivity

- No neuropathy (sensory and motor) > grade 1

- No active infection requiring antibiotics

- No other invasive malignancies or any evidence of other cancer within the past 5 years
except for nonmelanoma skin cancer

- No serious nonhealing wound, ulcer, or bone fracture

- No history of abdominal fistula or gastrointestinal perforation

- No history or evidence of seizures not controlled with standard medical therapy

- No intra-abdominal abscess within the past 28 days

- No active bleeding or pathologic conditions that carry a high risk of bleeding (e.g.,
bleeding disorder, coagulopathy, or tumor involving major vessels)

- 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

- No concurrent combination antiretroviral therapy for HIV-positive patients

- Recovered from prior surgery

- More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
or radiotherapy and recovered

- At least 1 week since prior hormonal therapy

- Concurrent hormone replacement therapy allowed

- At least 3 weeks since any other prior therapy, including immunologic agents

- One additional prior cytotoxic regimen for management of recurrent or persistent
endometrial cancer allowed

- 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

- More than 28 days since prior major surgery or open biopsy

- More than 7 days since prior minor surgery, fine needle aspirates, or core biopsies

- No prior cancer treatment that would preclude study compliance

- No prior noncytotoxic chemotherapy for management of recurrent or persistent
endometrial disease

- No prior VEGF Trap or other VEGF pathway-targeted therapy

- More than 5 years since prior radiotherapy to any portion of the abdominal cavity or
pelvis except for the treatment of endometrial cancer

- More than 3 years since prior radiotherapy for localized cancer of the breast,
head and neck, or skin

- Patient must remain free of recurrent or metastatic disease

- More than 5 years since prior chemotherapy for any abdominal or pelvic tumor except
for the treatment of endometrial cancer

- More than 3 years since prior adjuvant chemotherapy for localized breast cancer

- Patient must remain free of recurrent or metastatic disease

- Concurrent low-molecular weight heparin allowed for the prevention or treatment of
venous thromboembolic disease if condition is considered clinically stable with
treatment

- No other concurrent investigational agents

- No concurrent major surgery