ALK Gene Mutation, BRAF V600E, EGFR Gene Mutation, Non-Small Cell Carcinoma of Lung, TNM Stage 4, Non-Small Cell Lung Cancer, ROSE Cluster 1
Conditions
Brief summary
A comparison of baseline tumor characteristics in oncogene-driven cancers to tumor characteristics after early response to Tyrosine Kinase Inhibitor (TKI) targeted treatment will allow identification of early adaptive mechanisms of cell survival. This will facilitate targeting and termination of these survival/ resistance pathways before they develop with rational combinations of therapeutic agents to improve outcomes.
Interventions
None listed
Sponsors
University of Colorado, Denver
Study design
Observational model
OTHER
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Targetable Oncogene - Biopsy Cohort (includes blood draw) 1. Carry a diagnosis of locally advanced or stage IV NSCLC responsive to targeted therapies (per current NCCN guidelines) 2. Aged 18 years or older 3. ECOG 0-2 4. Have a histologically confirmed diagnosis of NSCLC harboring an activating mutation responsive to targeted therapy (per NCCN guidelines) 5. No prior systemic therapy for locally advanced or metastatic disease. 6. Planned treatment with targeted therapy specific to the oncogene driver mutation. 7. Patients must have at least one site of measurable disease ≥ 2cm. 8. Primary disease site or site of metastatic disease must be amenable to biopsy. 9. Patients must have the ability to understand and willingness to sign an informed consent document. Targetable Oncogene - Blood Draw Only Cohort 1. Carry a diagnosis of locally advanced or stage IV NSCLC responsive to targeted therapy (per NCCN guidelines) 2. Aged 18 years or older 3. ECOG 0-2 4. Have a histologically confirmed diagnosis of NSCLC harboring an activating mutation responsive to targeted therapy (per NCCN guidelines) 5. No prior systemic therapy or radiotherapy for metastatic lung cancer (surgery alone permitted) 6. Planned treatment with targeted therapy specific to the oncogene driver mutation. 7. Declines repeat biopsy option or does not have tumor site amenable to biopsy. 8. Patients must have the ability to understand and willingness to sign an informed consent document. Immunotherapy Cohort - Blood Draw Only 1. Have a histologically confirmed diagnosis of locally advanced or stage IV NSCLC without a treatable activating mutation that would be amenable to targeted therapy AND planned first line treatment with immunotherapy or chemotherapy plus immunotherapy. 2. Aged 18 years or older 3. ECOG 0-2 4. No prior systemic therapy or radiation therapy for lung cancer (surgery alone permitted) 5. Patients must have the ability to understand and willingness to sign an informed consent document.
Exclusion criteria
Targetable Oncogene - Biopsy Cohort (includes blood draw) 1. Concurrent health problem which would preclude tissue biopsy (e.g. hemophilia or other bleeding predisposition). 2. Patients whose only biopsy source would involve sampling an anatomic area that carries an unacceptably high procedural risk (e.g. pericardium or kidney) as deemed by the treating physician or by a proceduralist performing the biopsy. 3. Patients whose only biopsy source involves a sample that may not be evaluable due to insufficient genomic material (such as cerebrospinal or ascitic fluid) as deemed by the treating physician. . Targetable Oncogene Cohort and Immunotherapy Cohort - Blood Draw Only 1. Planned follow up on therapy outside of the University of Colorado Health System 2. Unwillingness to allow for residual clinical biopsy specimens to be utilized in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| gene expression changes | baseline and 2 weeks (+/- 1 week) for each patient. | change from baseline of tumor gene expression profile at 2 weeks. Global gene expression data will be collected using RNAseq |
| protein expression change | baseline and 2 weeks (+/- 1 week) for each patient. | change from baseline of protein gene expression profile at 2 weeks as measured by multiplex protein assay (proteins to be assayed include: e-cadherin, vimentin, fibronectin, CD4, CD8, CD14, CD16, CD206, PDL1, and CSF1R) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depth of Response | Study startup through 36 months | Correlation between the depths of tumor response (by RECIST v1.1) (percentage decrease in tumor size) with the presence of an EMT signature. |
Countries
United States
Contacts
CONTACTBrandi Kubala
PRINCIPAL_INVESTIGATORErin Schenk
University of Colorado, Denver
Outcome results
None listed