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