VEGF Trap in Treating Patients With Recurrent or Persistent Endometrial Cancer

Study Overview
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Brief Summary
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This phase II trial is studying the side effects and how well VEGF Trap works in treating patients with recurrent or persistent endometrial cancer. VEGF Trap may stop the growth of endometrial cancer by blocking blood flow to the tumor and by carrying tumor-killing substances directly to endometrial cancer cells.

Detailed Description
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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.

Official Title
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A Phase II Evaluation of VEGF-Trap (AFLIBERCEPT, NSC #724770, NCI-Supplied Agent) in the Treatment of Recurrent or Persistent Endometrial Carcinoma

Conditions
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Recurrent Endometrial Carcinoma

Intervention / Treatment
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* Biological: ziv-aflibercept


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (aflibercept)<br>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. | Biological: ziv-aflibercept<br> <br> * Other names: Zaltrap;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 Month Progression-free Survival | Number of participants who survived progression-free for more than 6 months. | At 6 monthsEvery other cycle during treatment for the first 6 months. | 
| Objective Tumor Response (RECIST 1.0) | RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate. | Every other cycle during treatment for the first 6 months, then every 3 months thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease; up to 5 years. | 
| Number of Participants With Incidence of Adverse Events at Least Possibly Related to Study Agent as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Adverse events at least possibly related to the study agent. | Assessed every cycle while on treatment, 30 days after the last cycle of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Progression-free Survival | Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. | Every other cycle during treatment for the first 6 months, then every 3 months thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease; up to 5 years. | 
| Duration of Overall Survival | Overall survival is defined as the duration of time from study entry to time of death or the date of last contact. | Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years. |