Carboplatin, Docetaxel, Bevacizumab, and Erlotinib Versus Chemotherapy Alone in Resected NSCLC

Study Overview
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Brief Summary
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Multicenter randomized phase II trial to examine the safety and efficacy of carboplatin, docetaxel, bevacizumab followed by maintenance bevacizumab and erlotinib in patients with completely resected stage IB, II, and select III NSCLC.

Official Title
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Randomized Phase II Trial of Adjuvant Carboplatin, Docetaxel, Bevacizumab, and Erlotinib Versus Chemotherapy Alone in Patients With Resected Non-Small Cell Lung Cancer

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Docetaxel/Carboplatin/Bevacizumab/Erlotinib
* Drug: Docetaxel/Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically-confirmed non-small cell lung cancer (adenocarcinoma, squamous, large cell and undifferentiated). Mixed small cell and non-small histologies are excluded. Patients with completely resected (R0) stage IB, II, and select III NSCLC. The following stages are eligible: IB T2 N0 IIA T1 N1 IIB T2 N1 IIB T3 N0 IIIA T3 N1 Bronchioalveolar carcinoma that presents as a single, solitary discrete nodule or mass may be included Patients determined to have N2 disease, that was not apparent radiologically preoperatively (and completely resected) can be included. Complete surgical resection defined as the appropriate pulmonary parenchymal resection including lobectomy, bilobectomy, sleeve lobectomy, and pneumonectomy with histologically confirmed negative bronchial margins. Patients treated by segmentectomy or wedge resection are not eligible for this study. Additionally all patients must have had either a mediastinal node dissection or at least, sampling of 2 mediastinal nodal stations (levels 4,7,and 9 for right-sided tumors, and levels 5,6,7, and 9 for left-sided tumors are suggested.) No evidence of metastatic disease ANC >= 1500, platelets >= 100,000 and hemoglobin >= 10.0. Total bilirubin <= ULN. AST and ALT and alkaline phosphatase must be WNL Serum creatinine <= 1.5mg/dl (If greater than 1.5, the creatinine clearance, calculated according to the Cockroft-Gault formula, must be >= 50ml/min). Patients may have had no previous chemotherapy, radiation therapy, angiogenesis inhibitor, or tyrosine kinase inhibitor for non-small cell lung cancer. Patients must be able to understand the nature of this study and give written informed consent. Age >= 18 years Ability to start treatment between 8 and 12 weeks following surgery. Ability to take oral medication. Exclusion Criteria: Patients with preoperative radiologic evidence of N2 disease by either PET or CT scan (i.e. radiological evidence of metastasis to ipsilateral mediastinal and subcarinal nodes) that is confirmed as N2 disease histologically are excluded. - PLEASE SEE EXCEPTION in section 3.1.2 of protocol Mixed small cell and non-small cell histologies Pulmonary carcinoid tumors Positive bronchial margins History of prior malignancy within 5 years with the exception of skin cancer or cervical carcinoma in situ. Women who are pregnant (positive pregnancy test) or breast-feeding. Subjects of childbearing potential or with partners of childbearing potential (women and men) must use effective birth control measures during treatment. Treatment with a non-approved or investigational drug within 30 days before day 1 of trial treatment. Patients with seizures not controlled with standard medical therapy. Patients with active infection requiring parenteral antibiotics Patients who have had major surgical procedure, open biopsy, or significant traumatic injury within 8 weeks of beginning study treatment or anticipation of need for major surgical procedure during the course of the study Fine needle aspiration, core biopsy or other minor surgical procedure (excluding placement of a vascular access device) within 7 days of beginning study treatment. Patients receiving thrombolytic therapy within 10 days of starting study treatment are also ineligible. Patients may receive prophylactic anticoagulation therapy, 1 mg coumadin daily for port clot prophylaxis. Patients with 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 >= 1 g of protein in 24hours to be eligible). Patients with serious nonhealing wound, ulcer, or bone fracture. Patients with evidence of bleeding diathesis or coagulopathy. Patients with history of hemoptysis defined as bright red blood of ½ teaspoon or more per episode) within 8 weeks prior to study treatment. History of myocardial infarction or unstable angina within 6 months of beginning study treatment. Inadequately controlled hypertension (defined as systolic blood pressure > 150 and /or diastolic blood pressure > 100 mmHg on antihypertensive medications). New York Heart Association (NYHA) grade II or greater CHF. Serious cardiac arrhythmia requiring medication. Symptomatic peripheral vascular disease. History of stroke or transient ischemic attack within 6 months prior to beginning bevacizumab. Any prior history of hypertensive crisis or hypertensive encephalopathy. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to beginning study treatment. ECOG Performance status > 1. Peripheral neuropathy> grade 1. Known hypersensitivity to any component of study drugs including platinum or to drugs formulated with polysorbate 80. Impaired oral absorption. Inability to comply with study and/or follow-up procedures.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Docetaxel/Carboplatin/Bevacizumab/Erlotinib<br> | Drug: Docetaxel/Carboplatin/Bevacizumab/Erlotinib<br>* Docetaxel 75mg/m2 IV D1 Carboplatin AUC=6 IV D1 Bevacizumab 15mg/kg IV D1 Docetaxel should be administered before carboplatin. After completion of four cycles of treatment, patients in Cohort A will then proceed with Maintenance treatment defined as follows: Maintenance Treatment for patients in Cohort A: Bevacizumab 15mg/kg IV D1 Erlotinib 150mg PO daily Treatment cycle = 21 days. Patients will complete 8 cycles (24 weeks) of maintenance therapy unless there is evidence of disease recurrence or unacceptable toxicity.<br>|
| Active Comparator: Docetaxel and Carboplatin<br> | Drug: Docetaxel/Carboplatin<br>* Adjuvant Treatment Cohort B: Docetaxel 75mg/m2 IV D1 Carboplatin AUC=6 IV D1 Docetaxel should be administered before carboplatin. Treatment cycle = 21 days. Patients in Cohort B will complete 4 cycles of treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free Survival | The length of time, in months, that patients were alive from the end of their treatment without any signs or symptoms of their disease. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Adverse Events occuring in >15% of patients | 2 years | 
| 2-year Survival | Proportion of patients known to still be alive 2 years after coming on study | 24 months | 
| Overall Survival (OS) | The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | 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, Resected, Carboplatin, Docetaxel, Bevacizumab, Erlotinib