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

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)

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

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Procedure: Stereotactic Radiosurgery; Drug: Erlotinib

Detailed Description

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
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • University of California at San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Lineberger Comprehensive Cancer Center
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • STO Taussig Cancer Center; Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Stereotactic Radiosurgery Followed by Erlotinib; Stereotactic Radiosurgery or Other Local Ablation Followed by Erlotinib	Procedure: Stereotactic Radiosurgery; 21 Gy daily for 5 days; Other Names: Cyberknife; Drug: Erlotinib; 150mg once daily; Other Names: Tarceva

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: Astellas Pharma Global Development, Inc.
• Investigators: Principal Investigator: Jared Weiss, MD, UNC at Chapel Hill

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 11, 2012
• Primary Completion (ACTUAL): March 15, 2019
• Study Completion (ACTUAL): March 15, 2019

Study Registration Dates

• First Submitted: April 5, 2012
• First Submitted That Met QC Criteria: April 5, 2012
• First Posted (ESTIMATE): April 9, 2012

Study Record Updates

• Last Update Posted (ACTUAL): January 12, 2021
• Last Update Submitted That Met QC Criteria: December 17, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: erlotinib; Phase II; Non small cell lung cancer; EGFR mutant; Lineberger; tarceva; cyberknife
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: LCCC 1123