Chemotherapy, Radiotherapy and Bevacizumab in Patients With Unresectable Stage III Non-Small-Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to see if this combination of chemotherapy plus radiation therapy and immunotherapy (with bevacizumab) expands treatment options for patients with non-small cell lung cancer.

Detailed Description
-----------------
The patients on this study will receive treatment in 3 stages of therapy. The first stage is Induction Therapy. This therapy is 7 weeks long. Patients will receive bevacizumab followed by pemetrexed followed by carboplatin all by vein once a week in weeks 1 and 4. During Induction patients will also receive radiation therapy daily, Monday through Friday, for 7 weeks (weeks 1-7). This is followed by 2 weeks of rest. During this rest period patients will have scans done to see how their disease has responded to treatment. The next stage of treatment is Consolidation Therapy. This stage is 10 weeks long. Patients will receive bevacizumab followed by pemetrexed followed by carboplatin all by vein once a week in weeks 10, 13 and 16. This is followed by 3 weeks rest. During week 19 patients will have scans to see how their disease has responded to treatment. The last stage of treatment is Maintenance Therapy. Patients will receive bevacizumab alone by vein every 3 weeks. Treatment will be given every three weeks for up to 9 treatments. (week 45)

Official Title
-----------------
A Phase II Study of Pemetrexed/Carboplatin/Radiotherapy and Bevacizumab in Patients With Unresectable Stage III Non-Small-Cell Lung Cancer

Conditions
-----------------
Lung Cancer

Intervention / Treatment
-----------------
* Drug: Bevacizumab
* Drug: Pemetrexed
* Procedure: Radiotherapy
* Other: Folic Acid
* Other: vitamin B12
* Drug: carboplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinically confirmed non-small cell lung cancer stage IIIA and selected stage IIIB Measurable or evaluable disease Be up and about and able to care for self Adequate kidney, liver and bone marrow function No prior treatment for this disease Must be able to give written informed consent Must be able to take folic acid, vitamin B12 and dexamethasone as described in the protocol Age 18 years or older Exclusion Criteria: Stage IV or IIIB patients with pleural or pericardial effusions Stage IIIB disease with contralateral mediastinal nodes greater than 4cm Squamous cell predominant tumors Pregnant or lactating women Patients with active infections History of another cancer within the last 5 years with the exception of skin cancer or cervical carcinoma in situ History of stroke, transient ischemic attacks, or acute MI within the past 6 months or any other serious cardiovascular disease Symptoms of peripheral vascular disease History of neurological disease Recent history of blood in the sputum or vomitus Non-healing wounds, ulcer or long bone fractures History of bleeding problems or coagulation problems History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 6 months History of uncontrolled hypertension Chronic use of non-steroidal anti-inflammatory medication not allowed on this study 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. You can then decide if you wish to participate.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Induction treatment included: carboplatin AUC=5, pemetrexed 500 mg/m2, and bevacizumab 15 mg/kg each administered intravenously weeks 1 and 4. Radiation was administered concurrently at a dose of 1.8 Gy/d weeks 1 to 7 to a total of 61.2 Gy per institutional guidelines. Consolidative therapy, following an 8-week break from chemoradiotherapy, included carboplatin AUC=6, pemetrexed 500 mg/m2, and bevacizumab 15 mg/kg each administered intravenously on week 16, repeated weeks 19 and 22. Folic acid (350 to 1,000 ug or equivalent) supplementation was administered orally beginning 1 to 2 weeks before the first dose of pemetrexed and continued daily until the patient discontinued study therapy. Vitamin B12(1,000ug) was administered by intramuscular injection 1 to 2 weeks before the first dose of study therapy and repeated every 9 weeks until the patient discontinued therapy. | Drug: Bevacizumab<br>* 15mg/kg week 1, 4, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, and 49.<br>* Other names: Avastin;Drug: Pemetrexed<br>* 500mg/m2 week 1, 4, 16, 19 and 22.<br>* Other names: Alimta;Procedure: Radiotherapy<br>* 1.8 Gy single daily fractions(Monday-Friday), to total dose 61.2 Gy (7 weeks)<br>* Other names: RT;Other: Folic Acid<br>* 350 to 1,000 ug or equivalent supplementation administered orally beginning 1 to 2 weeks before the first dose of pemetrexed and continued daily until the patient discontinues study therapy.<br>Other: vitamin B12<br>* 1,000ug administered by intramuscular injection 1 to 2 weeks before the first dose of study therapy and repeated every 9 weeks until the patient discontinues therapy.<br>Drug: carboplatin<br>* AUC=5 administered intravenously weeks 1 and 4.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | The objective benefit is defined as substantial shrinkage in tumor volume per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and is assessed by MRI or CT. Objective response = complete response + partial response. Complete Response (CR) is defined as the Disappearance of all target lesions; Partial Response (PR) is defined as >=30% decrease in the sum of the longest diameter of target lesions. | 18 months | 
| Overall Survival | Overall survival was defined as the interval between the date of study entry until the date of death | 18 months |