Erlotinib and SBRT in Treating Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

OBJECTIVES:

Primary

• To evaluate the effect of erlotinib and stereotactic body radiotherapy on 6-month progression-free survival of patients with locally advanced or metastatic non-small cell lung cancer.

Secondary

• To describe the actuarial rate of in-field local control and out-of-field disease progression in patients treated with this regimen.
• To evaluate the safety of this regimen in these patients.
• To evaluate overall survival of patients treated with this regimen.
• To evaluate the duration of erlotinib usage and time to initiation of third-line systemic therapy (chemotherapy or biologic agent) in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity. Beginning 1-4 weeks after the initiation of erlotinib hydrochloride, patients undergo stereotactic body radiotherapy.

After completion of study treatment, patients are followed every 3 months.

Inclusion criteria

Patients must meet all of the following inclusion criteria to be eligible for participation in this study:

• Patients must have biopsy proven NSCLC that is locally advanced or metastatic.
• Patients must have had failure of at least one prior chemotherapy regimen.
• Patients must not have started erlotinib therapy more than 4 weeks prior to the initiation of SBRT.
• Age ≥ 18 years
• Patients must have measurable disease at baseline.
• Patients can have up to only 6 discrete active extracranial lesions (≤3 in the liver and ≤3 in the lung) identified by PET scan and also seen on correlative plain film, CT scan, or MRI within 8 weeks prior to the initiation of SBRT.

• For patients who have received prior radiotherapy to the primary site in the lung, residual PET activity is difficult to interpret and will not be considered a site of active disease if the CT appearance is stable or improved over an interval of at least three months
• Patients who previously received radiotherapy to the primary site will be ineligible if there is CT evidence of disease progression within the past 3 months.
• Patients with previously un-irradiated primary sites will be potentially eligible, but special considerations apply (section 4.3.2).
• Up to 2 contiguous vertebral metastases will be considered a single site of disease.
• Patients must have a KPS >60
• AST, ALT & Alkaline phosphates must be ≤ 2.5X the upper limit of normal. Total bilirubin must be within the limit of normal.
• Patients should have adequate bone marrow function as defined by peripheral granulocyte count of ≥1500/mm³.
• Patients should have adequate renal function (serum creatinine ≤1.5 times the ULN).
• Females of childbearing potential should have a negative pregnancy test.
• Patients who would be receiving SBRT for lung tumors who are known or suspected by the treating radiation oncologist to have compromised lung function must have a documented forced expiratory volume in 1 second (FEV1) ≥ 1L.
• Patients must provide verbal and written informed consent to participate in the study.
• Total bilirubin: within normal institutional limits

Exclusion criteria

Patients who meet any of the following exclusion criteria are not to be enrolled in this study.

• Patients who previously received radiotherapy to the primary site with CT evidence of disease progression at the primary site within 3 months following the initial radiotherapy.
• Patients with either untreated brain metastases or brain metastases treated within the past three months are ineligible
• Patients with serious, uncontrolled, concurrent infection(s).
• Significant weight loss (>10%) in the prior 3 months.
• Because the tolerance dose of SBRT to the gastrointestinal tract is not established, patients with metastatic disease invading the esophagus, stomach, intestines, or mesenteric lymph nodes will not be eligible.
• Patients with cutaneous metastasis of NSCLC.
• Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cancers.
• Patients with more than 6 discrete extra-cranial lesions.
• Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
• Unwillingness to participate or inability to comply with the protocol for the duration of the study.
• Patients who are pregnant. Patients with reproductive capability will need to use adequate contraception during the time of participation in the study.
• Patients who have had prior EGFR inhibitors.