Rapid Plasma Genotyping For Early Initiation Of Erlotinib In EGFR Mutant Lung Cancer

Study Overview
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Brief Summary
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Patient with Non-Small Cell Lung Cancer (NSCLC) that might have a genetic change (mutation) in the Epidermal Growth Factor Receptor (EGFR) are invited to take part in this study. This research study is evaluating a new blood test that is capable of detecting an EGFR mutation in cancer without a biopsy.

Detailed Description
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This research study is a Phase II clinical trial. This research study will determine if a rapid blood test can be used to detect EGFR mutations in patients with newly diagnosed lung cancer and use that information to rapidly start patients on a pill-based therapy. This blood test has not previously been used to select patients for treatment with Erlotinib without confirming this finding on a biopsy.

Official Title
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Rapid Plasma Genotyping For Early Initiation Of Erlotinib In EGFR Mutant Lung Cancer

Conditions
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Epidermal Growth Factor Receptor, Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed metastatic NSCLC including recurrent disease EGFR genotype must not be known. However, pending EGFR tumor genotyping is allowed. --Participants with positive or pending EGFR mutation on plasma genotyping performed at the central lab are eligible for enrollment, and will not need to repeat initial plasma genotyping on study. Tissue must be available for genotyping or biopsy planned to obtain tissue for genotyping. Biopsy requirement may be waived if not technically feasible and plasma genotyping reveals an eligible EGFR mutation (exon 19 del/L858R). Determination of technical feasibility must be made independently of plasma genotyping results. Participants must possess at least two of the following clinical characteristics which enrich for EGFR mutations: smoked less than 10 pack years Asian race. Adenocarcinoma (including adenosquamous carcinoma) on histology or cytology. Participants must have measurable disease with at least one lesion that can be accurately measured in longest dimension as >2 cm with conventional imaging techniques or >1 cm with a spiral CT scan per RECIST v1.1. Participants must have progressive, advanced cancer as defined by one of the following: Newly diagnosed, untreated advanced disease Newly diagnosed, untreated metastatic recurrence of earlier stage disease (previous treatment of early stage disease allowed). Clinical determination of progressive disease on previous systemic therapy as evidenced by plan to change treatment. Any number of prior therapies are acceptable excluding previous EGFR kinase inhibitors. Age 18 years or older. ECOG performance status 0-2. Participant must be able to understand and give consent to participate in the study. Patient must be a candidate for systemic therapy with erlotinib based on clinical assessment. Patients must meet the following criteria before beginning therapy (Note: these are not required for initial study enrollment and plasma genotyping): ECOG performance status of 0-2 Platelets >75 AST & ALT < 3x the upper limit of normal Creatinine clearance > 30 mL/min by Cockroft-Gault No other contraindication to erlotinib Female participants of child-bearing age must agree to use adequate contraception (hormonal, barrier or abstinence) for the duration of the study while receiving erlotinib and undergo a pregnancy test. Any evidence or suspicion of pregnancy should be reported to the treating physician immediately. Male participants must agree to use adequate contraception for the duration of the study while receiving erlotinib Exclusion Criteria: Participants must not have had chemotherapy within the past 10 days. Participants must not have had prior treatment with an EGFR kinase inhibitor, EGFR directed therapy or investigational agent. Participants must not have residual adverse events from previous therapy greater than CTCAE v4.0 grade 2 at the time of registration. Participants must not have symptomatic brain metastases or brain metastases requiring steroids. Asymptomatic brain metastases not requiring steroids are acceptable. Participant must not have a history of allergy to erlotinib. Second primary cancer which is active and requiring treatment. Participants must not be pregnant or breastfeeding

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EGFR mutation Positive, Treatment With Erlotinib<br>Eligible EGFR mutations include exon 19 deletion or exon 21 L858R mutation. Erlotinib will be initially dosed at a pre-determine dosage daily, and it will be given on a 6-week cycle with treatment administered on an outpatient basis | Drug: Erlotinib<br> <br> * Other names: Tarceva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Number of participants who were alive with evidence of complete or partial response, evaluated using RECIST 1.1 criteria. Patients that underwent rapid plasma genotyping and had an EGFR mutation and who were treated with erlotinib were included in this calculation. | From date of erlotinib initiation until the date of first documented disease progression or date of death from any cause, whichever came first. ORR was assessed up to 21 months after erlotinib initiation. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Turnaround Time | The turnaround time from study registration to treatment initiation was recorded for the plasma genotyping strategy versus standard tumor genotyping. For rapid plasma genotyping, turnaround time is the time between ordering plasma genotyping and obtaining results; this time period was compared to the turnaround time of obtaining the tumor genotyping results. | Maximum 38 days | 
| Positive Predictive Value (PPV) And False Negative Rate Of Plasma Genotyping | Concordance between results of plasma genotyping and tumor genotyping, among patients with tissue available for standard genotyping | PPV and False Negative Rate can be assessed when plasma and tissue results are available for each patient; average plasma result turnaround time was 4 days, versus average of 20 days for tissue result turnaround time. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small Cell Lung Cancer, Epidermal Growth Factor Receptor