First-Line Treatment of A Comparison of 2 Treatments in Elderly Patients With Advanced NSCLC

Study Overview
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Brief Summary
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This trial will look at 2 different drug combinations that have well known safety profiles and are known to be active against non small cell lung cancer and combine them with bevacizumab, an experimental drug that has shown effectiveness when added to other drug combinations for advanced non-small cell lung cancer. The primary objective in this study is to see how well this combination of drugs keeps the cancer from getting worse in this elderly population of non-small cell lung cancer patients.

Detailed Description
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Patients in this study will be assigned to one of 2 treatment groups. The selection of the treatment groups will be done randomly by a computer. The first group, Cohort A, will receive bevacizumab 10mg/kg by vein over 30-90 minutes followed by pemetrexed 500 mg/m2 by vein over 10 minutes followed by gemcitabine 1500 mg/m2 by vein over 30-60 minutes. This regimen will be given on day 1 and day 15 of each treatment cycle. Each cycle is 28 days long. As long as their disease does not worsen patients can receive up to a maximum of 6 cycles of this combination chemotherapy. Following that they can receive bevacizumab alone once every 2 weeks as long as their disease does not worsen. The second group, Cohort B, will receive bevacizumab 15mg/kg by vein over 30-90 minutes followed by pemetrexed 500 mg/m2 by vein over approximately 10 minutes followed by carboplatin AUC=5 by vein over 30-60 minutes. This regimen will be given on day 1 of each treatment cycle. Each cycle is 21 days long. As long as their disease does not worsen patients can receive up to a maximum of 6 cycles of this combination chemotherapy. Following that they can receive bevacizumab alone once every 3 weeks as long as their disease does not worsen. In both regimens vitamin B12 injections and Folic Acid pills will be given to reduce the occurrence of side effects from the treatment. Each patient's disease will be evaluated at intervals by the proper scans or X-rays to see how well the cancer is responding to the treatment.

Official Title
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A Randomized Phase II Trial of Pemetrexed/Gemcitabine/Bevacizumab or Pemetrexed/Carboplatin/Bevacizumab in the First-Line Treatment of Elderly Patients With Advanced Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Pemetrexed
* Drug: Gemcitabine
* Drug: Bevacizumab
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed non-small cell bronchogenic carcinoma, (adenocarcinoma, or large cell carcinoma) Patients who have newly diagnosed unresectable stage III or stage IV disease are eligible. Must be at least 70 years of age Must have measurable disease by CT scan Must be able to be up and about and care for themselves May not have received prior treatment for stage III or IV disease Must have adequate white and red blood cells and platelets. Must be able to take Vitamin B12, Folic Acid and dexamethasone as stated in the study Must be able to understand the nature of this study and give written informed consent Adequate liver and kidney function Exclusion Criteria: Past or current history of cancer with the exception of treated non- melanoma skin cancer or carcinoma in-situ of the cervix, or other cancers cured by local therapy alone and have been disease free for five years Female patients who are pregnant or are lactating are ineligible History of unstable angina or myocardial infarction within 6 months prior to beginning bevacizumab Brain metastasis - cancer that has spread to the brain Major surgical procedure, open biopsy, or significant traumatic injury within 6 weeks of beginning bevacizumab or anticipation of need for major surgical procedure during the course of the study Full-dose oral or by vein anticoagulation or receiving anti-clotting therapy within 10 days of starting treatment Serious nonhealing wound, ulcer, or bone fracture Bleeding or clotting disorders Uncontrolled high blood pressure or serious heart arrhythmia requiring medication History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 6 months prior to beginning bevacizumab Chronic non-steroidal anti-inflammatory use is not allowed on study History of stroke or TIAs within the last 6 months Please Note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have.

Ages Eligible for Study
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Minimum Age: 70 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 |
| --- | --- |
| Experimental: Cohort A<br>Cohort A, will receive bevacizumab 10mg/kg by vein over 30-90 minutes followed by pemetrexed 500 mg/m2 by vein over 10 minutes followed by gemcitabine 1500 mg/m2 by vein over 30-60 minutes. This regimen will be given on day 1 and day 15 of each treatment cycle. Each cycle is 28 days long. As long as their disease does not worsen patients can receive up to a maximum of 6 cycles of this combination chemotherapy. Following that they can receive bevacizumab alone once every 2 weeks as long as their disease does not worsen. | Drug: Pemetrexed<br>* pemetrexed 500 mg/m2<br>* Other names: Alimta;Drug: Gemcitabine<br>* gemcitabine 1500 mg/m2<br>* Other names: Gemzar;Drug: Bevacizumab<br>* bevacizumab 10mg/kg bevacizumab 15mg/kg<br>* Other names: Avastin;|
| Experimental: Cohort B<br>Cohort B, will receive bevacizumab 15mg/kg by vein over 30-90 minutes followed by pemetrexed 500 mg/m2 by vein over approximately 10 minutes followed by carboplatin AUC=5 by vein over 30-60 minutes. This regimen will be given on day 1 of each treatment cycle. Each cycle is 21 days long. As long as their disease does not worsen patients can receive up to a maximum of 6 cycles of this combination chemotherapy. Following that they can receive bevacizumab alone once every 3 weeks as long as their disease does not worsen. | Drug: Pemetrexed<br>* pemetrexed 500 mg/m2<br>* Other names: Alimta;Drug: Bevacizumab<br>* bevacizumab 10mg/kg bevacizumab 15mg/kg<br>* Other names: Avastin;Drug: Carboplatin<br>* carboplatin AUC=5<br>* Other names: Paraplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression (TTP), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease | Time to Progression (TTP) is defined as the interval between the date of treatment initiation and the date of progressive disease. Progression is defined using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0). Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or unequivocal progression of non-target lesions or the appearance of one or more new lesions. | From the date of treatment initiation until the date of first documented PD or date of last study contact or date of other therapy begins up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment | Overall response rate (ORR) is defined as the percentage of patients who have a partial or complete response to therapy. Responses were assessed by the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.0). Complete Response: Disappearance of all target lesions, and disappearance of all non-target lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter of target lesions (taking as reference the baseline sum of longest diameters) | From date of treatment initiation to end of study treatment up to 18 months | 
| Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | OS is defined as the time from the date of study entry until the date of death due to any cause. In the absence of confirmation of death or lack of data beyond follow-up period, the survival time was censored to the last date the participant was known to be alive. | From date of study entry until the date of death from any cause or the date the patient was last known alive, up to 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non Small Cell Lung Cancer