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

SWOG Cancer Research Network

Status and phase

Completed

Phase 2

Conditions

Lung Cancer

Treatments

Biological: bevacizumab

Drug: erlotinib hydrochloride

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00436332

S0635 (Other Identifier)

CDR0000529756

U10CA032102 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

84 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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