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