Bevacizumab in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer or Primary Peritoneal Cancer

Study Overview
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Brief Summary
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This phase II trial is to see if bevacizumab works in treating patients who have persistent or recurrent ovarian epithelial cancer or primary peritoneal cancer. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the 6-month progression-free survival of patients with persistent or recurrent ovarian epithelial or primary peritoneal cancer treated with bevacizumab. II. Determine the nature and degree of toxicity of this drug in these patients. III. Determine the progression-free and overall survival of patients treated with this drug. IV. Determine the frequency of clinical response in patients treated with this drug. V. Determine the effect of this drug on initial performance status, age, and mucinous or clear cell histology in these patients. VI. Correlate biological and imaging markers with 6-month progression-free survival of patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. 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 Bevacizumab (Anti-VEGF Humanized Monoclonal Antibody) (NSC #704865) in the Treatment of Persistent or Recurrent Epithelial Ovarian or Primary Peritoneal Carcinoma

Conditions
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Primary Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer, Stage IV Ovarian Epithelial Cancer

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: Histologically confirmed ovarian epithelial or primary peritoneal carcinoma Recurrent or persistent after initial standard surgery or chemotherapy Incurable with standard surgery, chemotherapy, or radiotherapy At least 1 unidimensionally measurable target lesion At least 20 mm by conventional techniques At least 10 mm by spiral CT scan Outside the area of prior radiotherapy Accessible to guided core needle biopsy Received 1 prior platinum-based chemotherapy regimen (e.g., carboplatin, cisplatin, or another organoplatinum compound) for primary disease May have included high-dose therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment Patients with only 1 prior platinum-based chemotherapy regimen must have an initial treatment-free interval of less than 12 months Patients with an initial treatment-free interval of more than 12 months must have progressive disease after prior platinum-based chemotherapy regimen as second-line therapy No tumors involving major blood vessels No evidence of CNS disease (primary brain tumor or brain metastases) within the past 5 years Ineligible for higher priority Gynecologic Oncology Group (GOG) protocols (i.e., active phase III GOG protocols for the same patient population) Performance status - GOG 0-2 (patients who have received 1 prior regimen) Performance status - GOG 0-1 (patients who have received 2 prior regimens) Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 No known bleeding disorder or coagulopathy No active bleeding Bilirubin ≤ 1.5 times upper limit of normal (ULN) serum glutamate oxaloacetate transaminase (SGOT) ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN PT (INR) ≤ 1.5 (INR 2-3 if on stable dose of therapeutic warfarin or low molecular weight heparin) Partial thromboplastin time (PTT) < 1.2 times control Creatinine ≤ 1.5 times ULN Creatinine clearance > 60 mL/min No proteinuria, as indicated by 1 of the following: Negative urine dipstick Urine protein < 30 mg/dL Urine protein < 1,000 mg on 24-hour urine collection No clinically significant cardiovascular disease, including any of the following: Uncontrolled hypertension Myocardial infarction within the past 6 months Unstable angina within the past 6 months New York Heart Association class II-IV congestive heart failure Serious cardiac arrhythmia requiring medication Peripheral vascular disease ≥ grade 2 No stroke within the past 5 years No pathologic condition that carries a high risk of bleeding No significant traumatic injury within the past 28 days No other invasive malignancy within the past 5 years except nonmelanoma skin cancer No uncontrolled seizures within the past 5 years No neuropathy (motor and sensory) ≥ grade 2 No serious non-healing wound, ulcer, or bone fracture No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies No active infection requiring parenteral antibiotics No known claustrophobia that would preclude MRI tolerance No ferromagnetic implants or pacers Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 3 months after study treatment At least 3 weeks since prior immunologic therapy directed at malignancy No prior bevacizumab No other concurrent immunotherapy directed at malignancy One additional prior cytotoxic regimen for recurrent or persistent disease allowed No prior non-cytotoxic chemotherapy for recurrent or persistent disease No concurrent chemotherapy directed at malignancy At least 1 week since prior hormonal therapy directed at malignancy No concurrent hormonal therapy directed at malignancy Concurrent hormone replacement therapy allowed Recovered from prior radiotherapy No concurrent radiotherapy directed at malignancy At least 28 days since prior major surgery or open biopsy and recovered At least 7 days since prior core biopsy or placement of vascular access device No anticipated need for major surgical procedure during study participation At least 3 weeks since other prior therapy directed at malignancy No prior anticancer therapy that would preclude study entry

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. Courses repeat every 21 days 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 at 6 Months | 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 6 months. | 
| Tumor Response | 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 for the first 6 months; then every 3 months x 2 ; then every 6 months thereafter for up to 5 years. | 
| Number of Participants and Degree of Toxicity of Bevacizumab in This Cohort of Patients as Assessed by CTC. |  | Assessed every cycle while on treatment, 30 days after the last cycle of treatment, up to 5 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | The observed length of life from entry into the study to death or the date of last contact. | From study entry to death or last contact, up to 5 years. | 
| 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 for the first 6 months; then every 3 months x 2 ; then every 6 months therafter for up to 5 years. |