Epidermal Growth Factor Receptor, Non-Small Cell Lung Cancer
Conditions
Keywords
Non-Small Cell Lung Cancer, Epidermal Growth Factor Receptor
Brief summary
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
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.
Interventions
DRUGErlotinib
Sponsors
Astellas Pharma Inc
Dana-Farber Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Turnaround Time | Maximum 38 days | 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. |
| Positive Predictive Value (PPV) And False Negative Rate Of Plasma 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. | Concordance between results of plasma genotyping and tumor genotyping, among patients with tissue available for standard genotyping |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants With Plasma Genotyping Participants who enrolled to the study and had plasma genotyping | 43 |
| Total | 43 |
Baseline characteristics
| Characteristic | Participants With Plasma Genotyping |
|---|---|
| Age, Continuous | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 17 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment United States | 43 participants |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 15 Participants |
| Smoking Status Former Smoker | 14 Participants |
| Smoking Status Never Smoker | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
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.
Time frame: 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.
Population: A total of 6 participants were treated with erlotinib on study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| EGFR Exon 19 Positive Treatment With Erlotinib | Overall Response Rate | 4 Participants |
Secondary
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
Time frame: 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.
Population: 35 of the 42 participants with plasma genotyping results also had tumor genotyping results available, so PPV and false negative rate could be assessed in these 35 participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EGFR Exon 19 Positive Treatment With Erlotinib | Positive Predictive Value (PPV) And False Negative Rate Of Plasma Genotyping | Positive Predictive Value | 100 percentage |
| EGFR Exon 19 Positive Treatment With Erlotinib | Positive Predictive Value (PPV) And False Negative Rate Of Plasma Genotyping | False Negative Rate | 30 percentage |
Secondary
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.
Time frame: Maximum 38 days
Population: A total of 42 participants had plasma genotyping results available (1 of the 43 enrolled participants did not have plasma genotyping).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| EGFR Exon 19 Positive Treatment With Erlotinib | Turnaround Time | Turnaround Time: Plasma Genotyping | 4 days |
| EGFR Exon 19 Positive Treatment With Erlotinib | Turnaround Time | Turnaround Time: Tumor Genotyping | 20 days |