S0635: Erlotinib and Bevacizumab in Stage IIIB and IV Bronchioloalveolar Carcinoma

OBJECTIVES:

Primary

• Determine overall survival of patients with stage IIIB or IV bronchioloalveolar carcinoma (BAC) or adenocarcinoma with BAC features treated with erlotinib hydrochloride and bevacizumab.

Secondary

• Determine the progression-free survival of patients treated with this regimen.
• Compare, preliminarily, response as assessed by RECIST criteria vs response as assessed by a central computer-assisted image-analysis system in patients with measurable disease treated with this regimen.
• Assess the frequency and severity of toxicities of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib hydrochloride once daily on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for up to 2 years.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

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