Rapid Plasma Genotyping For Early Initiation Of Erlotinib In EGFR Mutant Lung Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: EGFR mutation Positive, Treatment With Erlotinib 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
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 2 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02115 |
| 3 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
Sponsors and Collaborators
- Dana-Farber Cancer Institute
- Astellas Pharma Inc
Investigators
- Principal Investigator: Geoffrey R Oxnard, MD, Dana-Farber Cancer Institute
Study Documents (Full-Text)
More Information
Publications
None provided.- 16-093
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Participants With Plasma Genotyping |
|---|---|
| Arm/Group Description | Participants who enrolled to the study and had plasma genotyping |
| Period Title: Plasma Genotyping | |
| STARTED | 43 |
| COMPLETED | 43 |
| NOT COMPLETED | 0 |
| Period Title: Plasma Genotyping | |
| STARTED | 11 |
| COMPLETED | 6 |
| NOT COMPLETED | 5 |
Baseline Characteristics
| Arm/Group Title | Participants With Plasma Genotyping |
|---|---|
| Arm/Group Description | Participants who enrolled to the study and had plasma genotyping |
| Overall Participants | 43 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
63
|
| Sex: Female, Male (Count of Participants) | |
| Female |
28
65.1%
|
| Male |
15
34.9%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
2
4.7%
|
| Not Hispanic or Latino |
38
88.4%
|
| Unknown or Not Reported |
3
7%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
17
39.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
3
7%
|
| White |
20
46.5%
|
| More than one race |
1
2.3%
|
| Unknown or Not Reported |
2
4.7%
|
| Region of Enrollment (participants) [Number] | |
| United States |
43
100%
|
| Smoking Status (Count of Participants) | |
| Former Smoker |
14
32.6%
|
| Never Smoker |
29
67.4%
|
Outcome Measures
| Title | Overall Response Rate |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| A total of 6 participants were treated with erlotinib on study. |
| Arm/Group Title | EGFR Exon 19 Positive Treatment With Erlotinib |
|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 6 |
| Count of Participants [Participants] |
4
9.3%
|
| Title | Turnaround Time |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| A total of 42 participants had plasma genotyping results available (1 of the 43 enrolled participants did not have plasma genotyping). |
| Arm/Group Title | Participants With Plasma Genotyping |
|---|---|
| Arm/Group Description | Participants who enrolled to the study and had plasma genotyping |
| Measure Participants | 42 |
| Turnaround Time: Plasma Genotyping |
4
|
| Turnaround Time: Tumor Genotyping |
20
|
| Title | Positive Predictive Value (PPV) And False Negative Rate Of Plasma Genotyping |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Participants With Plasma Genotyping |
|---|---|
| Arm/Group Description | Participants who enrolled to the study and had plasma genotyping |
| Measure Participants | 35 |
| Positive Predictive Value |
100
|
| False Negative Rate |
30
|
Adverse Events
| Time Frame | Adverse events were collected for the 6 participants who received erlotinib treatment from time of initiation of erlotinib through end of study. This time frame was a maximum of 21 months from initiation of erlotinib treatment to study completion. | |
|---|---|---|
| Adverse Event Reporting Description | CTCAE version 4.03 was used for reporting adverse events. Serious Adverse Events were not collected/assessed for the Plasma Genotyping Participants, unless felt to be related to the study procedures. No such SAEs occurred on this study. | |
| Arm/Group Title | EGFR Exon 19 Positive Treatment With Erlotinib | |
| Arm/Group Description | 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 | |
All Cause Mortality |
||
| EGFR Exon 19 Positive Treatment With Erlotinib | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | |
Serious Adverse Events |
||
| EGFR Exon 19 Positive Treatment With Erlotinib | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| EGFR Exon 19 Positive Treatment With Erlotinib | ||
| Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 1/6 (16.7%) | 1 |
| Cardiac disorders | ||
| Paroxysmal atrial tachycardia | 1/6 (16.7%) | 1 |
| Ear and labyrinth disorders | ||
| Ear pain | 1/6 (16.7%) | 1 |
| Gastrointestinal disorders | ||
| Abdominal pain | 2/6 (33.3%) | 3 |
| Constipation | 2/6 (33.3%) | 4 |
| Diarrhea | 3/6 (50%) | 3 |
| Dry mouth | 2/6 (33.3%) | 2 |
| Dyspepsia | 1/6 (16.7%) | 1 |
| Gastritis | 1/6 (16.7%) | 1 |
| Gastrointestinal disorders - Other, specify | 1/6 (16.7%) | 1 |
| Nausea | 2/6 (33.3%) | 2 |
| Vomiting | 1/6 (16.7%) | 1 |
| General disorders | ||
| Chills | 1/6 (16.7%) | 1 |
| Fatigue | 1/6 (16.7%) | 2 |
| Fever | 1/6 (16.7%) | 1 |
| General disorders and administration site conditions - Other, specify | 1/6 (16.7%) | 1 |
| Non-cardiac chest pain | 1/6 (16.7%) | 5 |
| Pain | 1/6 (16.7%) | 1 |
| Infections and infestations | ||
| Papulopustular rash | 1/6 (16.7%) | 1 |
| Paronychia | 1/6 (16.7%) | 1 |
| Skin infection | 1/6 (16.7%) | 1 |
| Investigations | ||
| Blood bilirubin increased | 1/6 (16.7%) | 1 |
| Serum amylase increased | 1/6 (16.7%) | 1 |
| Metabolism and nutrition disorders | ||
| Anorexia | 1/6 (16.7%) | 4 |
| Metabolism and nutrition disorders - Other, specify | 1/6 (16.7%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 1/6 (16.7%) | 1 |
| Back pain | 2/6 (33.3%) | 4 |
| Bone pain | 1/6 (16.7%) | 2 |
| Flank pain | 2/6 (33.3%) | 2 |
| Generalized muscle weakness | 3/6 (50%) | 3 |
| Muscle weakness trunk | 1/6 (16.7%) | 1 |
| Pain in extremity | 1/6 (16.7%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | 1/6 (16.7%) | 1 |
| Nervous system disorders | ||
| Dizziness | 3/6 (50%) | 3 |
| Dysgeusia | 1/6 (16.7%) | 1 |
| Headache | 2/6 (33.3%) | 2 |
| Psychiatric disorders | ||
| Anxiety | 1/6 (16.7%) | 1 |
| Depression | 1/6 (16.7%) | 1 |
| Insomnia | 1/6 (16.7%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 1/6 (16.7%) | 2 |
| Dyspnea | 1/6 (16.7%) | 4 |
| Pleural effusion | 1/6 (16.7%) | 2 |
| Skin and subcutaneous tissue disorders | ||
| Alopecia | 1/6 (16.7%) | 2 |
| Dry skin | 1/6 (16.7%) | 1 |
| Periorbital edema | 1/6 (16.7%) | 1 |
| Rash acneiform | 1/6 (16.7%) | 4 |
| Rash maculo-papular | 1/6 (16.7%) | 1 |
| Skin/subcutaneous tissue disorders; Other, specify | 1/6 (16.7%) | 4 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Geoffrey Oxnard, MD |
|---|---|
| Organization | Dana-Farber Cancer Institute |
| Phone | 617-632-6049 |
| geoffrey_oxnard@dfci.harvard.edu |
- 16-093