Non Small Cell Lung Carcinoma
Conditions
Brief summary
A study to determine the concordance of key actionable genomic alterations as assessed in tumor tissue and plasma from patients with non small cell lung carcinoma (NSCLC)
Detailed description
This is a prospective clinical study to characterize the concordance of key clinically relevant genomic alterations in tumor tissue (biopsy/excision/cytology) and liquid biopsy (blood) using the Genomic Health LBMP in patients with stage IV non squamous NSCLC, that are either newly diagnosed with metastatic disease or progressing on therapy (any line). Tissue biopsy and blood collection (liquid biopsy) should be less than eight weeks apart and with no new systemic antitumoral treatment given in the interval between the tissue biopsy and blood collection. Local assessment of tumor tissue samples will be performed at each participating institution as per their clinical standard of care practices and results from the local assessment of genomic alteration status will be used.
Interventions
None listed
Sponsors
Genomic Health®, Inc.
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must be 18 years or older. * Patients with stage IV non squamous NSCLC who are either newly diagnosed or progressing on any treatment (progression defined as increasing tumor size or new metastatic lesions on clinical or imaging assessment). * Patients with available tissue sample from a metastatic site or, if the patient presents with stage IV disease at diagnosis, from the primary tumor or a metastatic site. If a patient is progressing on EGFR targeted therapy (erlotinib, gefitinib, afatinib), tumor tissue sample is required only if available. * No new systemic anti-tumor therapy administered in the interval between the tissue biopsy and collection of the blood sample. (interval not to exceed eight weeks). Local radiation therapy is permitted. * Able and willing to read, understand and sign an informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization, or equivalent privacy law, where this is applicable.
Exclusion criteria
* Patients who are currently receiving therapy (targeted, immune- or chemotherapy) without sign of progression. * Patients with squamous NSCLC. * Patients with more than 8 weeks between collection of tumor specimen and collection of blood sample for analysis. (Not applicable for patients progressing on EGFR targeted therapy with no biopsy at progression) * Patients changing EGFR therapy due to toxicity or preference without documented disease progression. * Patients progressing on Osimertinib treatment. * Patients with brain metastases only. * Inability to comply with study and/or follow-up procedures. * Unable or unwilling to provide written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concordance of Genomic Alterations in EGFR Detected in Plasma Versus Tumor Tissue in Stage IV Non Squamous NSCLC Patients Who Are Newly Diagnosed or Progressing on Treatment | Time between patient tumor tissue biopsy and and blood collection, up to 8 weeks | Assess concordance of genomic alterations in EGFR detected in plasma (using the OncotypeSEQ Liquid Select assay) versus tumor tissue (assessed centrally using FoundationOne, or locally based on the patient's clinic) in stage IV non squamous NSCLC patients who are newly diagnosed or progressing on treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concordance of Genomic Alterations in ALK (EML4-ALK Fusions) Detected in Plasma Versus Tumor Tissue. | Time between patient tumor tissue biopsy and and blood collection, up to 8 weeks | Assess concordance of genomic alterations in ALK (EML4-ALK fusions) detected in plasma (using the OncotypeSEQ Liquid Select assay) versus tumor tissue (assessed centrally using FoundationOne OR locally based on the patient's clinic) in stage IV non squamous NSCLC patients who are newly diagnosed or progressing on treatment. |
| Percentage of Participants With EGFR T790M Alterations in Plasma in Patients Progressing on EGFR Targeting Therapy (Erlotinib, Gefitinib, Afatinib). | Time between patient tumor tissue biopsy and and blood collection (blood collected after the patient progressed on EGFR targeted therapy) | Detection of EGFR T790M alterations in plasma using the OncotypeSEQ Liquid Select assay. Progression on EGFR targeting therapy (erlotinib, gefitinib, afatinib) assessed clinically or radiologically |
Countries
Chile, France, Ireland, Japan, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A - NSCLC All Comers Regardless of Genomic Alteration Status Patients with non-squamous NSCLC regardless of genomic alteration status (newly diagnosed or progressing on therapy) | 121 |
| B - Progressing on EGFR Targeted Therapies Patients with non-squamous NSCLC progressing on erlotinib, gefitinib, or afatinib | 19 |
| Total | 140 |
Baseline characteristics
| Characteristic | B - Progressing on EGFR Targeted Therapies | A - NSCLC All Comers Regardless of Genomic Alteration Status | Total |
|---|---|---|---|
| Age, Customized Age, years | 67 years | 66 years | 66 years |
| ALK-EML4 Fusion Mutation Tested | NA Participants | 115 Participants | NA Participants |
| EGFR Mutation Tested | 19 Participants | 117 Participants | 136 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 91 Participants | 103 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 27 Participants | 33 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 14 Participants | 18 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 8 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 25 Participants | 31 Participants |
| Race (NIH/OMB) White | 9 Participants | 74 Participants | 83 Participants |
| Sex: Female, Male Female | 10 Participants | 61 Participants | 71 Participants |
| Sex: Female, Male Male | 9 Participants | 60 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Concordance of Genomic Alterations in EGFR Detected in Plasma Versus Tumor Tissue in Stage IV Non Squamous NSCLC Patients Who Are Newly Diagnosed or Progressing on Treatment
Assess concordance of genomic alterations in EGFR detected in plasma (using the OncotypeSEQ Liquid Select assay) versus tumor tissue (assessed centrally using FoundationOne, or locally based on the patient's clinic) in stage IV non squamous NSCLC patients who are newly diagnosed or progressing on treatment.
Time frame: Time between patient tumor tissue biopsy and and blood collection, up to 8 weeks
Population: Subjects who received EGFR mutation testing on both their tissue and plasma samples.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A - NSCLC All Comers Regardless of Genomic Alteration Status | Concordance of Genomic Alterations in EGFR Detected in Plasma Versus Tumor Tissue in Stage IV Non Squamous NSCLC Patients Who Are Newly Diagnosed or Progressing on Treatment | 94.0 Overall percent agreement (OPA) |
Secondary
Concordance of Genomic Alterations in ALK (EML4-ALK Fusions) Detected in Plasma Versus Tumor Tissue.
Assess concordance of genomic alterations in ALK (EML4-ALK fusions) detected in plasma (using the OncotypeSEQ Liquid Select assay) versus tumor tissue (assessed centrally using FoundationOne OR locally based on the patient's clinic) in stage IV non squamous NSCLC patients who are newly diagnosed or progressing on treatment.
Time frame: Time between patient tumor tissue biopsy and and blood collection, up to 8 weeks
Population: Subjects who received ALK (EML4-ALK fusion) mutation testing on both their tissue and plasma samples.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A - NSCLC All Comers Regardless of Genomic Alteration Status | Concordance of Genomic Alterations in ALK (EML4-ALK Fusions) Detected in Plasma Versus Tumor Tissue. | 95.7 Overall percent agreement (OPA) |
Secondary
Percentage of Participants With EGFR T790M Alterations in Plasma in Patients Progressing on EGFR Targeting Therapy (Erlotinib, Gefitinib, Afatinib).
Detection of EGFR T790M alterations in plasma using the OncotypeSEQ Liquid Select assay. Progression on EGFR targeting therapy (erlotinib, gefitinib, afatinib) assessed clinically or radiologically
Time frame: Time between patient tumor tissue biopsy and and blood collection (blood collected after the patient progressed on EGFR targeted therapy)
Population: Non-squamous NSCLC patients who progressed on erlotinib, gefitinib, or afatinib treatment and received mutation testing on both their plasma and tissue samples.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A - NSCLC All Comers Regardless of Genomic Alteration Status | Percentage of Participants With EGFR T790M Alterations in Plasma in Patients Progressing on EGFR Targeting Therapy (Erlotinib, Gefitinib, Afatinib). | 32 percentage of participants |