Dose Escalation of Bevacizumab With Ambulatory Blood Pressure Monitoring in Patients With Advanced Non-squamous NSCLC

Study Overview
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Brief Summary
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The purpose of this study is to see if higher dose of bevacizumab can be taken safely by some patients and if changes in the dose of bevacizumab have any effect on blood pressure.

Detailed Description
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Carboplatin and pemetrexed are FDA approved chemotherapy agents for patients with advanced non squamous non small cell lung cancer. Bevacizumab is also FDA approved in lung cancer , and the combination of all three drugs is promising. The doctors directing this research want to learn how to better personalize drug dosing of bevacizumab by identifying people who could safely take a higher dose of the drug.

Official Title
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A Randomized, Open-Label, Dose Escalation Study of Bevacizumab With Ambulatory Blood Pressure Monitoring in Previously Untreated Patients With Advanced Non-squamous Non-Small Cell Lung Cancer

Conditions
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Advanced Non-squamous Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Pemetrexed
* Drug: Carboplatin
* Drug: Bevacizumab 7.5 mg/kg
* Drug: Bevacizumab 15 mg/kg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically confirmed, newly diagnosed Stage IIIB, stage IV, or recurrent non-squamous NSCLC for which they have not received chemotherapy. Patients must have completed radiation therapy 2 weeks prior to enrollment. Patients may have received adjuvant therapy, provided the regimen included no more than one of the study agents. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension. Age >18 years. •Life expectancy of greater than 4 months. ECOG performance status of 0 or 1 Patients must have normal organ and marrow function Patients on anticoagulation are allowed. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Disease-Specific Patients who have had received prior chemotherapy (in the setting of recurrent disease, other than their original adjuvant therapy) Patients may not be receiving any other investigational agents. Patients with histologic evidence of predominantly squamous lung cell cancer General Medical Exclusions Inability to comply with study and/or follow-up procedures Malignancy other than superficial basal cell and superficial squamous of the skin or carcinoma in situ of the cervix within last five years Bevacizumab-Specific Exclusions Inadequately controlled hypertension Prior history of hypertensive crisis or hypertensive encephalopathy New York Heart Association Grade II or greater congestive heart failure History of myocardial infarction or unstable angina within 6 months prior to Day 1 History of stroke or transient ischemic attack within 6 months prior to Day 1 Known CNS disease, except for treated brain metastasis. Significant vascular disease within 6 months prior to Day 1 History of hemoptysis within 1 month prior to Day 1 Evidence of bleeding diathesis or significant coagulopathy Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1 History of diverticulitis, abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1 Serious, non-healing wound, active ulcer, or untreated bone fracture Proteinuria as demonstrated by a UPC ratio 1.0 at screening Known hypersensitivity to any component of bevacizumab Pregnancy (positive pregnancy test) or lactation. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present. Uncontrolled intercurrent illness including, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements. Any unstable condition that in the opinion of the investigator is likely to interfere with collection of accurate blood pressure measurement data . HIV-positive patients on combination antiretroviral therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

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
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br>Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once, followed three weeks later by Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg and bevacizumab every 3 weeks for two doses | Drug: Pemetrexed<br>* Pemetrexed 500 mg/m^2 intravenously over 10 minutes<br>Drug: Carboplatin<br>* Carboplatin at a dose calculated to produce an area under the concentration-time curve of 6 mg/ml•min intravenously over 30 minutes<br>Drug: Bevacizumab 7.5 mg/kg<br>* Bevacizumab at 7.5 mg/kg intravenously over 90 minutes<br>|
| Active Comparator: Group B<br>Carboplatin and Pemetrexed with Bevacizumab 7.5 mg/kg once, followed three weeks later by Carboplatin+Pemetrexed+Bevacizumab 15 mg/kg and bevacizumab every 3 weeks for two doses | Drug: Pemetrexed<br>* Pemetrexed 500 mg/m^2 intravenously over 10 minutes<br>Drug: Carboplatin<br>* Carboplatin at a dose calculated to produce an area under the concentration-time curve of 6 mg/ml•min intravenously over 30 minutes<br>Drug: Bevacizumab 7.5 mg/kg<br>* Bevacizumab at 7.5 mg/kg intravenously over 90 minutes<br>Drug: Bevacizumab 15 mg/kg<br>* Bevacizumab at 15 mg/kg intravenously over 90 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24 Hour Diastolic Blood Pressure (DBP) | The change for each patient was calculated as mean 24 hour DBP during cycle 2 - mean 24 hour DBP during cycle 1 | 2 cycles | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Percentage of patients with a complete or partial response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | 2 years | 
| Change in Tumor Size From Baseline |  | 2 years | 
| Progression Free Survival | Time to progression or death from any cause, whichever comes first | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bevacizumab, Non-squamous Non-Small Cell Lung Cancer, Ambulatory Blood Pressure Monitoring