S0636: Erlotinib and Bevacizumab in Never-Smokers With Stage IIIB or Stage IV Primary Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms
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: 89.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage IIIB non-small cell lung cancer; stage IV non-small 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 also may stop
      the growth of non-small cell lung cancer 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 IIIB or stage IV primary non-small cell lung cancer who
      have never smoked.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

               -  Adenocarcinoma

                    -  No component of squamous cell carcinoma present

               -  Incompletely resected or unresectable disease

          -  Stage IIIB or IV disease as defined below:

               -  Selected 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 lung cancer in a separate lobe after resection or radiotherapy
                       within the past 5 years OR multifocal lesions in > 1 lobe considered stage
                       IV disease

          -  New lesions occurring ≥ 5 years after resection may be considered a separate primary
             cancer and are not allowed if this is the only focus of lung cancer

          -  Measurable and/or nonmeasurable disease by CT scan, positron emission tomography scan,
             or MRI

               -  Disease must be present outside a previous radiotherapy field OR a new lesion
                  must be inside the port

               -  Measurable disease must be assessed within the past 28 days

               -  Nonmeasurable disease must be assessed within the past 42 days

               -  Pleural effusions, ascites, and laboratory parameters are not acceptable as the
                  only evidence of disease

          -  Must be a lifelong nonsmoker (< 100 cigarettes in lifetime)

          -  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/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  Total bilirubin normal

          -  SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases
             present)

          -  Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if bone metastases present)

          -  Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min

          -  Urine protein:creatinine ratio ≤ 0.5 OR urine protein < 1,000 mg by 24-hour urine
             collection

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  Hypertension allowed if controlled on medication prior to study enrollment

          -  Must be willing to provide prior smoking history

          -  No immediate life-threatening complications from malignancies

          -  No prior major medical condition, psychological condition, or social situation that
             would preclude study treatment

          -  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 either thrombosis or hemorrhage, including hemorrhagic or thrombotic
             stroke, or other CNS bleeding

          -  No serious nonhealing wound, ulcer, or bone fracture

          -  No other prior malignancy except for the following:

               -  Adequately treated basal cell or squamous cell skin cancer

               -  Adequately treated stage I or II cancer from which the patient is currently in
                  complete remission

               -  In situ cervical cancer

               -  Any other cancer from which the patient has been disease-free for 5 years

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  At least 7 days since prior fine-needle aspiration or core biopsy

          -  At least 28 days since prior radiotherapy (14 days for palliative radiotherapy) and
             recovered

          -  At least 28 days since prior surgery (e.g., thoracic or other major surgeries) and
             recovered

          -  At least 28 days since prior systemic chemotherapy

          -  Prior biologic therapy allowed

          -  No prior gefitinib, erlotinib hydrochloride, bevacizumab, or other targeted therapies
             against the epidermal growth factor receptor or vascular endothelial growth factor
             axes

          -  Concurrent stable, therapeutic anticoagulation therapy allowed (e.g., 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 concurrent surgery

          -  No other concurrent nonprotocol treatment (including chemotherapy, hormonal therapy,
             biological therapy, or radiotherapy) directed at this cancer