Avastin/Docetaxel/Carboplatin in Non-Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
The goal of this clinical research study is to evaluate the effectiveness of Avastin® in combination with docetaxel and carboplatin in the treatment of lung cancer. The safety of this combination will also be studied.

Detailed Description
-----------------
Avastin® is a humanized monoclonal antibody that binds to vascular endothelial growth factor (VEGF). VEGF plays an important role in the growth of both normal and abnormal blood vessels. Avastin® is designed to prevent or slow down the growth of cancer cells by blocking the effects of VEGF. Docetaxel and carboplatin are standard chemotherapy drugs that have been approved by the FDA for the treatment of NSCLC. Docetaxel and carboplatin are designed to work by stopping the division of cancer cells. If you are found to be eligible, you will begin receiving Avastin®, docetaxel, and carboplatin. Avastin®, carboplatin, and docetaxel will be given by vein once every 3 weeks. The first dose of Avastin® will be given over 90 minutes. The second dose of Avastin® will be given over 60 minutes. All other doses of Avastin® will be given over 30 minutes. Carboplatin and docetaxel will always be given over 30 minutes. They will be given on the same day every 3 weeks (1 cycle). You may receive up to 6 cycles of treatment. You will receive standard premedication with dexamethasone to help decrease the risk of side effects. Dexamethasone will be taken before you receive your docetaxel infusion. During the study, you will have blood tests (about 2 teaspoons) every 3 weeks to look at your blood counts. These samples will be used only for routine lab tests. You will be seen by a physician every 3 weeks and given a physical exam. Your blood pressure will be monitored, and you will be asked about any side effects you are experiencing. A performance status evaluation will also be done. In addition, you will have a urine test every 2 cycles of treatment. After 2 cycles of treatment (6 weeks), you will have a chest x-ray and computerized tomography (CT) or magnetic resonance imaging (MRI) scan to evaluate the status of the disease. These will be repeated every 2 cycles. Your continued participation in this study depends on how your cancer responds to the study drugs. Your doctor may decide to take you off this study if you experience significant side effects or your medical condition worsens. You may continue receiving bevacizumab for as long as your cancer responds to study treatment. You will be followed-up on by phone or at routine clinic visits for at least 12 months to monitor your condition and disease status. This is an investigational study. Avastin® has been approved by the FDA for the treatment of colorectal cancer. Docetaxel and carboplatin are FDA approved and commercially available. The use of these drugs together in this study is experimental. A total of 50 patients will take part in this study. All participants will be enrolled at M. D. Anderson.

Official Title
-----------------
A Phase II Evaluation of Avastin in Combination With Docetaxel and Carboplatin as Chemotherapy in Patients With Metastatic Non-Small Cell Lung Cancer

Conditions
-----------------
Non-Small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: Bevacizumab (Avastin)
* Drug: Carboplatin
* Drug: Docetaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women, at least 18 years old, with histologically confirmed, advanced stage IIIB or IV NSCLC for whom no curative options exist and for whom docetaxel and carboplatin is a reasonable treatment option; At least 1 target lesion that is unidimensionally measurable as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) and has not been previously irradiated; Eastern Cooperative Oncology Group Performance Status of 0 or 1, (determined within 2 weeks prior to receiving study medication; Ability to understand and adhere to the protocol requirements, and give informed consent Use of effective means of contraception (men and women) in subjects of child-bearing potential. Child-bearing potential is defined as follows: A woman of childbearing potential is a sexually mature woman who has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses at any time in the preceding 12 consecutive months). Exclusion Criteria: Patients who have had docetaxel in nonradiosensitizing therapy Patients who have received prior full dose systemic chemotherapy for NSCLC (ie neoadjuvant, adjuvant, or metastatic) within the last 6 months. Eastern Cooperative Oncology Group (ECOG) status of 2 or greater Screening clinical laboratory values:*absolute neutrophil count (ANC) of <1,500/µL *Platelet count of <75,000/µL * international normalized ratio (INR) >/= 1.5 *T bilirubin elevation above normal (MDACC upper normal limit is 1.0 mg/dL) *Serum creatinine of >2.0 mg/dL *Hemoglobin of <9 mg/dL (may be transfused or receive epoetin alfa [e.g., Epogen®] to maintain or exceed this level) *The pt is ineligible if: 1.alk phos>5xULN; 2.AST or ALT >5xULN; 3.alk phos >1xULN but </= 2.5xULN AND AST or ALT >1.5xULN but </=5xULN;4.alk phos >2.5xULN but </=5xULN AND AST or ALT > 1xULN but</= 1.5xULN; 5.alk phos >2.5xULN but</=5xULN AND AST or ALT >1.5xULN but </=5xULN Inability to comply with study and/or follow-up procedures History of other disease, active infection, metabolic dysfunction , physical examination finding, or clinical laboratory finding which is uncontrolled requiring medical intervention giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications. Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a bevacizumab cancer study Prior exposure to anti-VEGF therapy Blood pressure of > 140/90 mmHg as documented in two consecutive blood pressure readings within 4 hours Any prior history of hypertensive crisis or hypertensive encephalopathy New York Heart Association (NYHA) Grade II or greater congestive heart failure History of myocardial infarction or unstable angina within 6 months History of stroke or transient ischemic attack within 6 months Significant vascular disease (e.g., aortic aneurysm, aortic dissection) Evidence of bleeding diathesis or coagulopathy Presence of central nervous system or brain metastases at any time Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0 Pregnant (positive pregnancy test) or lactating Proteinuria at screening as demonstrated by either: Urine protein:creatinine (UPC) ratio > 1.0 at screening OR Urine dipstick for proteinuria > 2+ (patients discovered to have > 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate < 1g of protein in 24 hours to be eligible). History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0 Serious, non-healing wound, ulcer, or bone fracture Lung carcinoma of squamous cell histology or any histology in close proximity to a major vessel, cavitation. History of hemoptysis (bright red blood of 1/2 teaspoon or more) Full dose anticoagulation, chronic use of Aspirin (>325 mg/day) or NSAIDs Inability to comply with study and/or follow-up procedures

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: Avastin + Docetaxel + Carboplatin<br>Avastin 15 mg/kg intravenously (IV) every 3 weeks. Docetaxel 75 mg/m2 IV every 3 weeks. Carboplatin AUC 6 IV every 3 weeks. | Drug: Bevacizumab (Avastin)<br>* 15 mg/kg intravenously (IV) every 3 weeks<br>* Other names: rhuMAb-VEGF;Drug: Carboplatin<br>* AUC 6 IV every 3 weeks<br>* Other names: Paraplatin®;Drug: Docetaxel<br>* 75 mg/m2 IV every 3 weeks<br>* Other names: Taxotere;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression-Free Survival (PFS) | Bevacizumab has recently been demonstrated to prolong overall survival when added to carboplatin and paclitaxel for chemotherapy-naı¨ve patients with nonsquamous nonsmall-cell lung cancer (NSCLC). However, the effects of combining bevacizumab with other standards, front-line, platinum-based doublets have not been extensively explored.We designed this single treatment arm, phase 2 trial to determine whether the combination of carboplatin, docetaxel, and bevacizumab is tolerable and prolongs progression-free survival of chemotherapy-naı¨ve patients with advanced, on squamous NSCLC. | Baseline up to 12 months or disease progression/death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS)- 5 Years | Secondary endpoints of the study included the assessment of overall survival, disease control rate (CR þPR þ SD, defined by RECIST16), and evaluation of the safety profile of this triple-agent regimen. All patients who received at least 1 dose of the study drug were analyzed for efficacy and toxicity endpoints. | Baseline start of treatment to death, assessed up to 6 years | 
| Disease Control Rate | 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. | Baseline start of treatment to death, assessed up to 6 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Non-Small Cell Lung Cancer, Lung Cancer, Bevacizumab, Carboplatin, Docetaxel, Avastin, NSCLC, Anti-VEGF monoclonal antibody, rhuMAb-VEGF, Paraplatin®, Taxotere