Paclitaxel, Bevacizumab and Pemetrexed in Patients With Untreated, Advanced Non-Small Cell Lung Cancer Using Web-Based Data Collection, Patient Self-Reporting of Adverse Effects and Automated Response Assessment

Study Overview
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Brief Summary
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The purpose of this study is to determine the percentage of patients with non-small cell lung cancer that will experience a shrinkage of their tumors following treatment with three medications given together: paclitaxel, pemetrexed (Alimta®), and bevacizumab (Avastin®). Each of these medications has been approved by the FDA for patients that have not received any treatment for their lung cancer. This study is designed to study the effects of all three drugs given at the same time. Each of these medications has been studied in lung cancer and is commercially available. Paclitaxel and pemetrexed are traditional chemotherapy drugs. Bevacizumab is a monoclonal antibody, which means that it attaches to a specific target. Bevacizumab attaches to a protein in the blood stream called Vascular Endothelial GrowthFactor (VEGF). VEGF helps tumors grow new blood vessels to feed themselves, and bevacizumab is thought to help block this new growth of blood vessels and starve the tumors of the nutrients they need.

Detailed Description
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In this clinical trial, we also will be studying other things. We want to learn more about how to manage side effects patients may develop during chemotherapy. Cancer patients may develop side effects during treatment, such as nausea, pain, fatigue, diarrhea, constipation, or shortness of breath. These symptoms may be due to the cancer itself, or due to treatments like chemotherapy drugs or radiation therapy. Doctors and nurses often ask patients about their symptoms, because an important part of cancer treatment is to make patients feel as well as possible. If patients do not feel well, we may need to change the way we are treating them or prescribe therapies that will decrease their symptoms. The best way to find out how the patient is feeling is to ask them directly. We are interested in developing new ways to ask patients about how they are feeling, using the Internet. A special new website called STAR (Symptom Tracking and Reporting for Patients) has been developed to help patients record this information, so that their doctors and nurses can review it during clinic appointments. This study is designed to help us see if STAR is a helpful way for us to keep track of information about patients' symptoms and quality of life. As part of this study, a computerized (automated) technique of determining the size of the patients tumor(s) before and after treatment will be used. This has been tested in the past and found to be more accurate. The automated technique of determining tumor size will be used with the routine CT scans that the patient will have as part of the study. This automated method of measuring the tumor(s) will allow us to know sooner whether this drug treatment is causing the disease to shrink. The information from STAR and the automated tumor measurements are going to be placed on a very secure Internet site. This will provide the doctor with all of the information needed to determine if this drug combination is working for the patient and whether to continue this study. Also, if there is a tumor sample from a biopsy done in the past, it will be analyzed for a protein that may be present in the lung cancer.

Official Title
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A Phase II Trial of Paclitaxel, Bevacizumab and Pemetrexed in Patients With Untreated, Advanced Non-Small Cell Lung Cancer Using Web-Based Data Collection, Patient Self-Reporting of Adverse Effects and Automated Response Assessment

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Paclitaxel
* Drug: Pemetrexed
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed Non-Small Cell Lung Cancer at MSKCC Clinical stage IIIB or IV. Measurable disease as per RECIST Greater than 6 months since receiving neo-adjuvant or adjuvant chemotherapy for Non-Small Cell Lung Cancer. Age ≥ 18 years. Karnofsky performance status of ≥ to 70. Marrow and organ function as follows: WBC ≥ to 4000/mm3 Platelets ≥ to 160,000 Bilirubin ≤ to 1.2mg/dL Creatinine clearance ≥ to 40mL/min AST and/or /ALT ≤ 37 Units/L (if one of these elevated, must be ≤ 2.5 ULN) Systolic blood pressure ≤ to 150mmHg or diastolic blood pressure ≤ to 100 mmHg). The subject is able to read and comprehend English text from a computer screen. Women of childbearing potential and sexually active men enrolled in the study must agree to practice effective contraception. Exclusion Criteria: Squamous cell carcinoma. Prior treatment with paclitaxel, pemetrexed or bevacizumab for NSCLC. Prior systemic anticancer therapy for advanced NSCLC. Symptomatic brain metastases with evidence of hemorrhage. Radiation therapy to greater than 25% of the bone marrow within 30 days of starting treatment. Peripheral neuropathy greater than grade 1. Malignancies within the past 5 years other than non-melanoma skin cancer. Patients with other serious medical illnesses including, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements. History of hemoptysis. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess. History of myocardial infarction or stroke within 6 months prior to enrollment. Pregnancy or lactation.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paclitaxel, Bevacizumab & Pemetrexed<br>During each 28-day cycle, paclitaxel, pemetrexed and bevacizumab will be given intravenously on days 1 and 15. Paclitaxel will be administered at 90mg/m^2 over 60 minutes on days 1 and 15. Pemetrexed 500mg/m^2 will be administered over 10 minutes on days 1 and 15. Bevacizumab will be given at 10mg/kg over 20 minutes on days 1 and 15 | Drug: Paclitaxel<br>* Day 1: Paclitaxel (90 mg/m^2 over 60 minutes) Day 15: Paclitaxel (90 mg/m^2 over 60 minutes)<br>Drug: Pemetrexed<br>* Day 1: Pemetrexed (500 mg/m^2 over 10 minutes) Day 15 Pemetrexed (500 mg/m2 over 10 minutes)<br>Drug: Bevacizumab<br>* Day 1:Bevacizumab (10 mg/kg over 20 minutes) Day 15: Bevacizumab (10 mg/kg over 20 minutes)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (CR + PR by RECIST) Paclitaxel, Pemetrexed, and Bevacizumab in Patients With Advanced Non-Small Lung Cancer Who Have Received no Prior Treatment for Metastatic Disease. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BEVACIZUMAB (AVASTIN), PEMETREXED (ALTIMA), TAXOL (PACLITAXEL), 08-109