Biomarker Analysis in Tumor and Blood Samples from Patients with Stage IV Non-small Cell Lung Cancer and EGFR, ALK, ROS1, or BRAF Mutations Undergoing Targeted Therapy
This research trial studies biomarkers in tumor and blood samples from patients with stage IV non-small cell lung cancer and EGFR, ALK, ROS1, or BRAF mutations who are undergoing targeted therapy. Studying biomarkers in the laboratory may help doctors learn more about differences found between pretreatment and early treatment tumor samples from patients with stage IV lung cancer.
Inclusion Criteria
- TARGETABLE ONCOGENE BIOPSY COHORT (INCLUDES BLOOD DRAW): Carry a diagnosis of stage IV non-small cell lung cancer (NSCLC) with an activating mutation documented to respond to an EGFR TKI, ALK or ROS1 fusion or BRAF V600E activating mutation
- TARGETABLE ONCOGENE BIOPSY COHORT (INCLUDES BLOOD DRAW): Eastern Cooperative Oncology Group (ECOG) 0-2
- TARGETABLE ONCOGENE BIOPSY COHORT (INCLUDES BLOOD DRAW): Have a histologically confirmed diagnosis of NSCLC harboring an EGFR, ALK, ROS1 or BRAF V600E activating mutation
- TARGETABLE ONCOGENE BIOPSY COHORT (INCLUDES BLOOD DRAW): No prior oncogene targeted therapy for metastatic disease, chemotherapy, immunotherapy permitted (bevacizumab, cetuximab permitted)
- TARGETABLE ONCOGENE BIOPSY COHORT (INCLUDES BLOOD DRAW): Planned treatment with targeted therapy specific to the oncogene driver mutation
- TARGETABLE ONCOGENE BIOPSY COHORT (INCLUDES BLOOD DRAW): Patients must have at least one site of measurable disease >= least 2 cm
- TARGETABLE ONCOGENE BIOPSY COHORT (INCLUDES BLOOD DRAW): Primary disease site or site of metastatic disease must be amenable to biopsy
- TARGETABLE ONCOGENE BIOPSY COHORT (INCLUDES BLOOD DRAW): Patients must have the ability to understand and willingness to sign an informed consent document
- TARGETABLE ONCOGENE BLOOD DRAW ONLY COHORT: Carry a diagnosis of stage IV NSCLC with an activating mutation documented to respond to an EGFR TKI, ALK or ROS1 fusion or BRAF V600E activating mutation
- TARGETABLE ONCOGENE BLOOD DRAW ONLY COHORT: ECOG 0-2
- TARGETABLE ONCOGENE BLOOD DRAW ONLY COHORT: Have a histologically confirmed diagnosis of NSCLC harboring an EGFR, ALK, ROS1 or BRAF V600E activating mutation
- TARGETABLE ONCOGENE BLOOD DRAW ONLY COHORT: No prior chemotherapy, immunotherapy, targeted therapy or radiation therapy for lung cancer (surgery alone permitted)
- TARGETABLE ONCOGENE BLOOD DRAW ONLY COHORT: Planned treatment with targeted therapy specific to the oncogene driver mutation
- TARGETABLE ONCOGENE BLOOD DRAW ONLY COHORT: Declines repeat biopsy option or does not have tumor site amenable to biopsy
- TARGETABLE ONCOGENE BLOOD DRAW ONLY COHORT: Patients must have the ability to understand and willingness to sign an informed consent document
- IMMUNOTHERAPY COHORT (BLOOD DRAW ONLY): Have a histologically confirmed diagnosis of stage IV NSCLC without a treatable activating mutation or rearrangement (e.g., KRAS, HRAS, NRAS, NF1)… AND planned first line treatment with immunotherapy or chemotherapy plus immunotherapy
- IMMUNOTHERAPY COHORT (BLOOD DRAW ONLY): ECOG 0-2
- IMMUNOTHERAPY COHORT (BLOOD DRAW ONLY): No prior chemotherapy, immunotherapy, or radiation therapy for lung cancer (surgery alone permitted)
- IMMUNOTHERAPY COHORT (BLOOD DRAW ONLY): Patients must have the ability to understand and willingness to sign an informed consent document
Exclusion Criteria
- TARGETABLE ONCOGENE BIOPSY COHORT
- Concurrent health problem which would preclude tissue biopsy (e.g. hemophilia or other bleeding predisposition)
- Patients whose only source of biopsiable disease is intracranial, pleural effusion or any lesion that is deemed unsafe to biopsy by the treating physician or interventional radiology
- TARGETABLE ONCOGENE BLOOD DRAW ONLY COHORT AND NON-TARGETABLE ONCOGENE COHORT
- Planned follow up on therapy outside of the University of Colorado, Anschutz Medical Campus
- Unwillingness to allow for residual clinical biopsy specimens to be utilized in this study
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03042221.
Locations matching your search criteria
United States
Colorado
Aurora
PRIMARY OBJECTIVES:
I. Identify differences between pretreatment and early treatment tumor samples in patients whose tumors contain activating mutations and who will be treated with targeted agents as first-line therapy.
II. Measurement of gene expression signatures of pre-and early treatment tumors.
III. Measurement of immunohistochemistry biomarkers of pre- and early treatment tumors.
SECONDARY OBJECTIVES:
I. Identify pre-therapy predictive markers that can be used to determine which tumors will undergo mesenchymal transformation (EMT) or activation of other bypass pathways following targeted therapy.
II. Determine if there is a correlation between the depths of tumor response (by Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1) (percentage decrease in tumor size) with the presence of an EMT signature.
III. Estimate success rate of early rebiopsy in obtaining tumor samples that have evaluable material for ribonucleic acid (RNA) sequencing (Seq) and other analyses.
IV. Determine adverse event rate associated with rapid second biopsy.
EXPLORATORY OBJECTIVES:
I. Determine if there is an association between progression free survival and bypass pathway activation status.
II. Determine whether there is evidence of bypass pathway activation in circulating tumor cells.
III. Determine whether the composition and proportions of circulating immune cells in the peripheral blood correlate with response to first line targeted therapy.
IV. Assess presence of immune cells within the tumor microenvironment and potential association with response to first line therapy.
V. Determine if local and circulating immunity differs between patients with activating mutations on targeted therapy and patients who receive immunotherapy as first line standard of care therapy.
OUTLINE:
Patients undergo tumor biopsy at prior to the start of systemic therapy (baseline), at the time of toxicity evaluation (2 weeks), at the time of first response assessment, and at time of progression. Patients also undergo collection of blood. Samples undergo genomic analysis via direct sequencing of oncogenes, fluorescence in situ hybridization, ribonucleic acid (RNA) sequencing, multiplex ion beam imaging, immunohistochemistry, proximity ligation assay, and real-time polymerase chain reaction.
Trial PhaseNo phase specified
Trial Typebasic science
Lead OrganizationUCHealth University of Colorado Hospital
Principal InvestigatorErin Schenk
- Primary ID15-2316
- Secondary IDsNCI-2017-01774
- ClinicalTrials.gov IDNCT03042221