S0635: Erlotinib and Bevacizumab in Stage IIIB and IV Bronchioloalveolar Carcinoma
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Adenocarcinoma, Bronchiolo-Alveolar
Intervention: bevacizumab; erlotinib hydrochloride
Intervention MeSH terms: Bevacizumab; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 84.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; bronchoalveolar cell lung cancer; adenocarcinoma of the lung

Summary:

      RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in
      different ways. Some block the ability of tumor cells to grow and spread. Others find tumor
      cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop
      the growth of tumor cells by blocking blood flow to the tumor. Giving erlotinib together with
      bevacizumab may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving erlotinib together with bevacizumab
      works in treating patients with stage III or stage IV non-small cell lung cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Biopsy-proven* bronchioloalveolar carcinoma (BAC) or BAC variants (e.g.,
             adenocarcinoma with BAC features, BAC with invasive adenocarcinoma) meeting the
             following criteria:

               -  Incompletely resected or unresectable disease

               -  No component of squamous cell carcinoma

               -  Disease staged as 1 of the following:

                    -  Stage IIIB disease (T4 [cytologically confirmed malignant pleural effusion
                       OR pleural tumor foci that are separate from direct pleural invasion by the
                       primary tumor], any N, M0)

                    -  Stage IV disease (any T, any N, M1 [distant metastases present])

                         -  Recurrent disease in a separate lobe after prior resection within the
                            past 5 years; multifocal lesions in > 1 lobe; or any disease that is
                            recurrent after surgery or radiotherapy is considered stage IV disease

               -  Tumor may be multifocal or diffuse NOTE: *Cytology specimens, including bronchial
                  brushing, washings, or fine needle aspiration specimens, alone are not acceptable
                  for diagnosis

          -  Measurable or nonmeasurable disease by chest CT scan

               -  Pleural effusions, ascites, and laboratory parameters are not acceptable as only
                  evidence of disease

               -  Disease must be present outside field of prior radiotherapy OR a new lesion must
                  be inside port

          -  Treated brain metastases allowed provided the patient is asymptomatic and do not
             require steroids

        PATIENT CHARACTERISTICS:

          -  Zubrod performance status 0-2

          -  Absolute neutrophil count ≥ 1,500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Total bilirubin normal

          -  AST or AST ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases
             are present)

          -  Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if bone metastases are present)

          -  Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min

          -  Urine protein:creatinine ratio ≤ 0.5 OR urine protein < 1 g by 24-hour urine
             collection

          -  Willing to provide prior smoking history

          -  No hemoptysis ≥ ½ teaspoon within the past 28 days

          -  No clinical history of pulmonary or upper respiratory hemorrhage > grade 2 within the
             past 6 months or > grade 1 within the past 28 days

          -  No history of thromboses or hemorrhage, including hemorrhagic or thrombotic stroke, or
             other CNS bleeding

          -  No uncontrolled hypertension

          -  No serious nonhealing wound, ulcer, or bone fracture

          -  No other prior malignancy except for any of the following:

               -  Adequately treated basal cell or squamous cell skin cancer

               -  In situ cervical cancer

               -  Adequately treated stage I or II cancer that is currently in complete remission

               -  Any other cancer from which the patient has been disease free for 5 years

          -  Not pregnant or nursing

          -  Fertile patients must use effective contraception

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  Recovered from prior therapy

          -  At least 28 days since prior radiotherapy (14 days for palliative radiotherapy)

          -  At least 28 days since prior surgery (thoracic or other major surgeries)

          -  More than 7 days since prior fine-needle aspiration or core biopsy

          -  At least 28 days since prior systemic chemotherapy or biologic therapy

          -  No prior gefitinib hydrochloride, erlotinib hydrochloride, or bevacizumab

          -  No other prior anti-epidermal growth factor receptor or anti-vascular endothelial
             growth factor therapies

          -  Concurrent stable, therapeutic anticoagulation therapy allowed (i.e., warfarin or low
             molecular weight heparin), provided the patient has no history of bleeding
             complications on anticoagulation or an inability to establish a stable therapeutic
             regimen for anticoagulation

          -  No other concurrent anticancer therapy, including surgery, chemotherapy, hormone
             therapy, biologic therapy, or radiotherapy