Stereotactic Radiosurgery or Other Local Ablation Then Erlotinib in Epidermal Growth Factor Receptor (EGFR)

Study Overview
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Brief Summary
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- Progression free survival after locally ablative therapy and erlotinib in EGFR patients progressed after EGFR-TKI therapy

Detailed Description
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Primary Objectives - To estimate progression free survival (PFS) after locally ablative therapy and erlotinib in EGFR-mutant NSCLC patients who progressed on prior EGFR-TKI therapy Secondary Objectives To evaluate local control of sites previously progressive on erlotinib following stereotactic radiosurgery (SRS) followed by erlotinib To estimate overall survival (OS) after locally ablative therapy and erlotinib in EGFR-mutant NSCLC patients who progressed on prior EGFR-TKI therapy To characterize the toxicity of SRS To characterize the toxicity of erlotinib when preceded by SRS Exploratory Objectives To explore if VeriStrat results at initial progression are associated with longer PFS or OS after study treatment To explore if VeriStrat results following completion of SRS are associated with longer PFS or OS after re-initiation of erlotinib To explore whether poor VeriStrat signatures ever turn to good signatures with the study therapy, and to explore PFS and OS of patients whose signature changes

Official Title
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Phase II Study of Stereotactic Radiosurgery or Other Local Ablation Followed by Erlotinib for Patients With Epidermal Growth Factor Receptor(EGFR) Mutation Who Have Previously Progressed on an Epidermal Growth Factor Receptor-tyrosine Kinase Inhibitor (EGFR-TKI)

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Procedure: Stereotactic Radiosurgery
* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent 18 years of age or older Histologically or cytologically confirmed stge IV EGFR-mutant NSCLC History of previous response to EGFR-TKI defined by a RECIST 1.1 criteria Progressive disease following EGFR-TKI therapy Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Adequate organ and marrow function Negative urine or serum pregnancy test for female patients Patients who can have children must agree to adequate contraception Exclusion Criteria: Unresolved chronic toxicities greater than 2, measured by CTCAE v4 Treatment with any FDA approved or experimental cancer treatment following progression on EGFR-TKI Any history of previous greater than grade 3 toxicity attributable to erlotinib Pregnant or lactating female Any previous radiation to sites of planned Stereostatic Radiosurgery History of another malignancy Concomitant anticancer therapy, immunotherapy, or radiation therapy (within 4 weeks) Evidence of severe or uncontrolled systemic diseases Known hypersensitivity reaction or idiosyncrasy to erlotinib Psychological, familial, sociological, or geographical conditions Any other condition in investigator's opinion jeopardize compliance with protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: For all patients, all sites of progressive disease will be treated with local ablation (primarily stereotactic radiosurgery) followed by the EGFR-TKI erlotinib until disease progression.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Stereotactic Radiosurgery Followed by Erlotinib<br>Stereotactic Radiosurgery or Other Local Ablation Followed by Erlotinib | Procedure: Stereotactic Radiosurgery<br>* 21 Gy daily for 5 days<br>* Other names: Cyberknife;Drug: Erlotinib<br>* 150mg once daily<br>* Other names: Tarceva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Progression Free Survival | Progression free survival (PFS) after locally ablative therapy and erlotinib in EGFR-mutant NSCLC patients who progressed on prior EGFR-tyrosine kinase inhibitor (TKI) therapy reported as percentage of participants who are alive and without progressive disease at 3 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or the appearance of new lesions. | 3 months after Initiation of Stereostatic Radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Local Control of Sites on Erlotinib Following Stereotactic Radiosurgery (SRS) | Count of subjects who had local control of sites previously progressive on erlotinib following SRS followed by erlotinib. Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), local control is defined as Complete Response (CR), Disappearance of all target lesions; or Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; in sites ablated by SRS. | Initiation of Stereotactic Radiotherapy every 6 to 12 weeks until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months | 
| Median Overall Survival | To estimate overall survival (OS) after locally ablative therapy and erlotinib in EGFR-mutant, NSCLC patients who progressed on prior EGFR-TKI therapy measured as length of time from start of treatment until date of death from any cause | up to 5 years after end of treatment | 
| Toxicity Rate From Stereotactic Radiosurgery (SRS) | Toxicity of SRS will be measured by NCI CTCAE version 4 following completion of SRS, but prior to erlotinib re-initiation. The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. | From initiation to the end of SRS, up to 15 days | 
| Toxicity Rate Attributed to Erlotinib | Toxicity of erlotinib will be graded using the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE version 4) which is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. | from end of SRS to end of erlotinib treatment (median duration of 5.7 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non small cell lung cancer, EGFR mutant, Phase II, erlotinib, tarceva, cyberknife, Lineberger