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

Non Small Cell Lung Cancer Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01573702
• Other study ID #: LCCC 1123
• Status: Completed
• Phase: Phase 2
• Start date: December 11, 2012
• Est. completion date: March 15, 2019

Study information

• Verified date: December 2020
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: March 15, 2019
• Est. primary completion date: March 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non Small Cell Lung Cancer

Intervention

Procedure:
• Stereotactic Radiosurgery
21 Gy daily for 5 days

Drug:
• Erlotinib
150mg once daily

Locations

Country	Name	City	State
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	STO Taussig Cancer Center; Cleveland Clinic	Cleveland	Ohio
United States	East Carolina University	Greenville	North Carolina
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	University of California at San Francisco	San Francisco	California
United States	Swedish Cancer Institute	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center	Astellas Pharma Global Development, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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)