S0636: Erlotinib and Bevacizumab in Never-Smokers With Stage IIIB or Stage IV Primary Non-Small Cell Lung Cancer

SWOG Cancer Research Network

Status and phase

Completed

Phase 2

Conditions

Lung Cancer

Treatments

Drug: erlotinib hydrochloride

Biological: bevacizumab

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00445848

CDR0000531056

S0636 (Other Identifier)

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 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.

Full description

OBJECTIVES:

Primary

Assess overall survival of patients with stage IIIB or IV primary non-small cell lung adenocarcinoma who have never smoked and are treated with erlotinib hydrochloride and bevacizumab.

Secondary

Assess progression-free survival of patients treated with this regimen.
Assess the response rate (confirmed and unconfirmed, complete and partial) in a subset of patients with measurable disease treated with this regimen.
Evaluate the frequency and severity of toxicities associated with this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib hydrochloride 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 periodically for up to 3 years.

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

Enrollment

89 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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