Bevacizumab 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 how well bevacizumab works in treating patients with recurrent or persistent endometrial cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor.

Detailed Description
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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.

Official Title
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A Phase II Evaluation of Bevacizumab (NCI-Supplied Agent: NSC# 704865, IND # 7921) in the Treatment of Recurrent or Persistent Endometrial Carcinoma

Conditions
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Recurrent Endometrial Carcinoma

Intervention / Treatment
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* Biological: bevacizumab
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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

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 (bevacizumab)<br>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. | Biological: bevacizumab<br>* Given IV<br>* Other names: rhuMAb VEGF;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival Greater Than 6 Months | Disease Progression is at least a 20% increase in the sum of longest dimension (LD) of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. | 6 months | 
| Best Tumor Response | Response is measured according to Response Evaluation Criteria in Solid Tumors Criteria (RECIST v 1.0): Complete Response (CR) is disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial Response (PR) is 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. Disease Progression is at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Stable Disease is any condition not meeting the above criteria. Indeterminate is defined as having no repeat tumor assessments following initiation of study therapy for reasons unrelated to symptoms or signs of disease. | study entry through completion | 
| Number of Patients With Toxicity of Bevacizumab as Assessed by CTCAE v3.0 in This Cohort of Patients. |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 for the first 6 months; then every 4 cycles until progression or death, up to 5 years. | 
| 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. | 
| Initial Performance Status | Performance Status 0 = Fully active, able to carry on all pre-disease performance without restriction Performance Status 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature, e.g., light housework, office work Performance Status 2 = Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours. | Baseline | 
| Histologic Grade | G1 - Highly differentiated adenomatous carcinoma. G2 - Differentiated adenomatous carcinoma with partly solid areas. G3 - Predominantly solid or entirely undifferentiated carcinoma. | Baseline |