Bevacizumab in Treating Patients With Persistent or Recurrent Cancer of the Cervix

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 cancer of the cervix. 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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OBJECTIVES: I. Determine the cytostatic antitumor activity of bevacizumab, in terms of 6-month progression-free survival (PFS), in patients with persistent or recurrent squamous cell carcinoma of the cervix. II. Determine the nature and degree of toxicity of this drug in these patients. III. Estimate the distribution of PFS and overall survival for patients treated with this drug. IV. Determine the frequency of clinical response (partial and complete) in patients treated with this drug. V. Determine the role of age and initial performance status as prognostic factors in patients treated with this drug. VI. Determine whether biological and imaging markers are associated with clinical efficacy of this drug, such as 6-month PFS, in these patients. OUTLINE: This is a multicenter study. Patients receive bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 3 weeks 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. PROJECTED ACCRUAL: A total of 19-51 patients will be accrued for this study within 11-38 months.

Official Title
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A Phase II Trial of Bevacizumab (rhuMAB VEGF) (NSC #704865) in the Treatment of Persistent and Recurrent Squamous Cell Carcinoma of the Cervix (Group A)

Conditions
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Cervical Squamous Cell Carcinoma, Recurrent Cervical 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 persistent or recurrent squamous cell carcinoma (SCC) of the cervix Patients must have received at least 1, but no more than 2, prior cytotoxic chemotherapy regimens for advanced, metastatic, or recurrent SCC of the cervix Chemotherapy administered as a radio-sensitizer does not count as 1 regimen Documented disease progression At least 1 unidimensionally measurable lesion* At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan No tumor involving major blood vessels No history or physical evidence of CNS disease, including primary or metastatic brain tumor Ineligible for a higher priority Gynecological Oncology Group (GOG) protocol (if one exists), including any active GOG phase III protocol for the same patient population Performance status - GOG 0-2 (if received 1 prior regimen) Performance status - GOG 0-1 (if received 2 prior regimens) Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 No known bleeding disorder or coagulopathy No other active bleeding or pathologic condition that would confer a high risk of bleeding Bilirubin ≤ 1.5 times upper limit of normal (ULN) SGOT ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN INR ≤ 1.5 (or 2-3 for patients on a stable dose of therapeutic warfarin or low molecular weight heparin) PTT < 1.2 times control Creatinine ≤ 1.5 times ULN Creatinine clearance > 60 mL/min No proteinuria Urine protein < 1+ on dipstick or < 30 mg/dL Urine protein < 1000 mg by 24-hour urine collection No clinically significant cardiovascular disease No uncontrolled hypertension No myocardial infarction or unstable angina within the past 6 months No New York Heart Association grade II-IV congestive heart failure No serious cardiac arrhythmia requiring medication No grade II or greater peripheral vascular disease No history of stroke within the past 5 years No greater than grade 1 sensory or motor neuropathy No active infection requiring parenteral antibiotics No serious nonhealing wound, ulcer, or bone fracture No history or physical evidence of seizures not controlled with standard medical therapy No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies No other invasive malignancy within the past 5 years except nonmelanomatous skin cancer No significant traumatic injury within the past 4 weeks Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 3 months after completion of study treatment No prior bevacizumab At least 3 weeks since prior immunologic agents for SCC of the cervix See Disease Characteristics Recovered from prior chemotherapy No prior non-cytotoxic chemotherapy for persistent or recurrent disease At least 1 week since prior hormonal therapy for SCC of the cervix Concurrent hormone replacement therapy allowed See Disease Characteristics Recovered from prior radiotherapy Recovered from recent prior surgery At least 4 weeks since prior major surgical procedure or open biopsy At least 1 week since prior placement of vascular access device or core biopsy No concurrent major surgical procedure At least 3 weeks since other prior therapy for SCC of the cervix No prior anticancer therapy that would preclude study therapy No concurrent anticoagulants other than those required to maintain the patency of indwelling IV catheters No concurrent chronic daily aspirin greater than 325 mg/day or other nonsteroidal anti-inflammatory medications that are known to inhibit platelet function at doses used for chronic inflammatory diseases

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 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 | Whether or not the patient survived progression-free for at least 6 months. | Every other 3-week treatment cycle for 6 months | 
| Maximum Severity of Each Adverse Event Per Patient, Graded According to Common Toxicity Criteria Version 2.0 | The maximum severity of each adverse event per patient, graded according to Common Toxicity Criteria version 2.0, is reported. Events were restricted to those reported as at least possibly related to study drug. | Every cycle and 30 days after the end of treatment. (average 5 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 during treatment and at the time of treatment discontinuation. (average 5 months) | 
| 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 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 | 
| 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 | 
| Age at Enrollment |  | Baseline |