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

UNC Lineberger Comprehensive Cancer Center32 enrolled

Overview

\- Progression free survival after locally ablative therapy and erlotinib in EGFR patients progressed after EGFR-TKI therapy

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Non Small Cell Lung Cancer

Interventions

Stereotactic RadiosurgeryPROCEDURE

21 Gy daily for 5 days

ErlotinibDRUG

150mg once daily

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (8)

University of California at San Francisco

San Francisco, California, United States

University of Colorado Cancer Center

Aurora, Colorado, United States

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

East Carolina University

Outcomes

Primary Outcomes

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.

Time frame: 3 months after Initiation of Stereostatic Radiotherapy

Secondary Outcomes

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.

Time frame: 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

Time frame: 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.

Data from ClinicalTrials.gov

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