Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery
Condition: Lung Adenocarcinoma; Lung Adenosquamous Carcinoma; Lung Large Cell Carcinoma; Lung Squamous Cell Carcinoma; Minimally Invasive Lung Adenocarcinoma; Stage IIIA Lung Non-Small Cell Cancer AJCC v7; Stage IIIB Lung Non-Small Cell Cancer AJCC v7
MeSH terms: Carcinoma; Adenocarcinoma; Adenocarcinoma of Lung; Carcinoma, Adenosquamous; Carcinoma, Large Cell; Adenocarcinoma, Bronchiolo-Alveolar
Intervention: Bevacizumab; Cisplatin; Docetaxel; Etoposide; Filgrastim; Pegfilgrastim; Radiation Therapy
Intervention description: Given IV; Given IV; Given IV; Given IV; Given SC; Given SC; Undergo thoracic radiotherapy
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Cisplatin; Docetaxel; Etoposide; Etoposide phosphate; Podophyllotoxin; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Lenograstim; Immunoglobulin G
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This clinical trial studies combination chemotherapy, radiation therapy, and bevacizumab in
      treating patients with newly diagnosed stage III non-small cell lung cancer that cannot be
      removed by surgery. Drugs used in chemotherapy, such as cisplatin, etoposide, and docetaxel,
      work in different ways to stop the growth of [cancer/tumor] cells, either by killing the
      cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy
      uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as bevacizumab, may
      interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the
      growth of tumor cells by blocking blood flow to the tumor. Giving more than one drug
      (combination chemotherapy) together with radiation therapy and bevacizumab may kill more
      tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed single, primary, bronchogenic, non-small
             cell lung cancer (NSCLC)

               -  Newly diagnosed disease

               -  Unresectable disease

               -  No more than 1 parenchymal lesions on same or opposite sides of the lungs

          -  Meets 1 of the following stage criteria:

               -  Stage IIIA (N2) disease meeting the following criteria:

                    -  N2 mediastinal lymph nodes must be multiple and/or bulky on CT scan or x-ray
                       so that the patient is not a candidate for induction chemotherapy or
                       chemoradiotherapy followed by surgical resection

                    -  N2 status must be documented by ≥ 1 of the following methods:

                         -  Histologically or cytologically confirmed N2 disease by exploratory
                            thoracotomy, thoracoscopy, mediastinoscopy, mediastinotomy, Chamberlain
                            procedure, Wang needle biopsy (WNB), fine needle aspiration (FNA) under
                            bronchoscopic or CT guidance, or any other method

                         -  Node positive by fludeoxyglucose-positron emission tomography (FDG-PET)
                            scan

                         -  Nodes > 3 cm on CT scan

                         -  Paralyzed left true vocal cord with separate left lung primary distinct
                            from anterior-posterior window nodes on CT scan

               -  Stage IIIB disease meeting ≥ 1 of the following criteria:

                    -  Histologically or radiographically confirmed positive N3 nodes*, documented
                       by ≥ 1 of the following methods:

                         -  FNA, core needle biopsy (CNB), or excisional biopsy of supraclavicular
                            N3 nodes

                         -  Biopsy of contralateral mediastinal N3 nodes by mediastinoscopy,
                            mediastinotomy, or thoracotomy

                         -  FNA, CNB, or WNB under CT or bronchoscopic fluoroscopic guidance of
                            enlarged contralateral N3 mediastinal nodes

                         -  Contralateral mediastinal nodes > 3 cm on CT scan

                         -  Node positivity by FDG-PET scan

                         -  Right-sided primary with paralyzed left true vocal cord

                    -  T4 lesions of any size that invade the mediastinum, heart, great vessels,
                       trachea, esophagus, vertebral body, or carina, documented by ≥ 1 of the
                       following methods:

                         -  Written documentation of type of T4 extent if patient had a prior
                            exploratory thoracotomy or thoracoscopy

                         -  T4 involvement of the trachea or carina by direct bronchoscopic
                            visualization

                         -  T4 involvement of the heart, esophagus, aorta, or vertebral body by CT
                            scan, MRI, or transesophageal ultrasound

                         -  T4 involvement of the mediastinum by CT scan or MRI if, in the absence
                            of the above organ involvement, there is soft tissue extension directly
                            into the mediastinal space**

          -  Meets 1 of the following risk criteria:

               -  Low risk disease, meeting the following criteria:

                    -  Non-squamous cell NSCLC, including adenocarcinoma, bronchoalveolar cell
                       carcinoma, or large cell carcinoma

                         -  If mixed histology, the squamous cell carcinoma component must be < 50%

                         -  Histology or cytology from involved mediastinal or supraclavicular
                            lymph nodes allowed if a separate distal primary lesion is clearly
                            evident on radiographs (i.e., second biopsy not required)

                    -  No primary tumor with cavitation and/or tumor within 1 cm of a major vessel

                    -  No hemoptysis (i.e., bright red blood ≥ ½ teaspoon) in the past 28 days

               -  High-risk* disease, meeting ≥ 1 of the following criteria:

                    -  Squamous cell NSCLC

                         -  If mixed histology, the squamous cell component must be ≥ 50%

                    -  Tumor with any histology that has cavitation or is located within 1 cm of a
                       major vessel

                         -  No aortic involvement

                    -  Any histology and hemoptysis (i.e., bright red blood ≥ ½ teaspoon) within
                       past 28 days

          -  Measurable or nonmeasurable disease by CT scan or MRI

               -  Pleural effusions, ascites, and laboratory parameters are not acceptable as the
                  only evidence of disease

          -  No pleural effusion except for small pleural effusion visible on CT scan or MRI alone

          -  No pericardial effusions

          -  No metastatic disease involving the contralateral chest, liver, or adrenals confirmed
             by CT scan of the upper abdomen or by chest CT scan with complete liver and adrenals
             in the report

          -  Patients must be offered participation in SWOG-S9925 (Lung Cancer Specimen Repository
             Protocol)

          -  No brain metastases by CT scan or MRI

          -  No evidence of cavitation

          -  Creatinine normal

          -  Creatinine clearance ≥ 50 mL/min

          -  FEV_1 ≥ 2.0 liters OR predicted FEV_1 of the contralateral lung > 800 mL

          -  Absolute neutrophil count ≥ 1,500/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  Urine protein: creatinine ratio ≤ 0.5 by urinalysis OR urine protein < 1,000 mg by
             24-hour urine collection

          -  INR < 1.5

          -  Zubrod performance status 0-1

          -  No sensory neuropathy > grade 1

          -  No cerebrovascular accident within the past 6 months

          -  No myocardial infarction or unstable angina within the past 6 months

          -  No uncontrolled hypertension

          -  No New York Heart Association class II-IV congestive heart failure

          -  No serious cardiac arrhythmia requiring medication

          -  No clinically significant peripheral vascular disease

          -  No evidence of bleeding diathesis or coagulopathy

          -  No pathologic condition other than lung cancer that carries a high risk of bleeding

          -  No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
             human antibodies

          -  No serious, nonhealing wound, ulcer, or bone fracture

          -  No other prior malignancy except adequately treated basal cell or squamous cell skin
             cancer, in situ cervical cancer, adequately treated stage I or II cancer for which the
             patient is currently in complete remission, or other cancer for which the patient has
             been disease-free for 5 years

          -  Not pregnant or nursing

               -  No nursing during and for ≥ 6 months after the last dose of bevacizumab

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for ≥ 6 months after the
             last dose of bevacizumab

          -  Must have pre-treatment simulation demonstrating a V20 ≤ 35% with planned radiation
             dose of 6,480 cGy

          -  No prior surgical resection

               -  Prior exploratory thoracotomy, mediastinoscopy, excisional biopsy, or similar
                  surgery allowed for diagnosing, staging, or determining potential resectability
                  of lung tumor

          -  No prior chemotherapy or radiotherapy for lung cancer

          -  No prior radiotherapy to the neck or thorax

          -  At least 4 weeks since prior thoracic or other major surgery (excluding
             mediastinoscopy) and recovered

          -  More than 7 days since prior FNA, CNB, or mediastinoscopy

          -  No other concurrent anticancer therapy, including chemotherapy, radiotherapy, or
             biologic agents

          -  No other concurrent investigational drugs

          -  No concurrent major surgical procedures

          -  No concurrent full-dose anticoagulants (e.g., low-molecular weight and unfractionated
             heparin or warfarin)

               -  Low-dose warfarin (i.e., 1 mg) is allowed to prevent clotting of an infusaport or
                  central line

          -  No concurrent brachytherapy, radiopharmaceuticals, high linear energy transfer
             radiation (i.e., fast neutrons), particle therapy (i.e., protons, carbon, or helium),
             and/or altered fractionation schemes

          -  No concurrent intensity-modulated radiotherapy

          -  No concurrent prophylactic contralateral hilar or supraclavicular lymph node
             radiotherapy