Early Rebiopsy to Identify Biomarkers of Tumor Cell Survival Following EGFR, ALK, ROS1 or BRAF TKI Therapy

Early Rebiopsy to Identify Mechanisms and Biomarkers of Tumor Cell Survival Following Systemic Therapy for Lung Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer; ALK Gene Mutation; EGFR Gene Mutation; BRAF V600E; Non-Small Cell Carcinoma of Lung, TNM Stage 4; ROSE Cluster 1

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Brandi Kubala; Phone Number: 303-724-1657; Email: brandi.kubala@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado, Cancer Center
      • Contact: Brandi Kubala; Phone Number: 303-724-1657; Email: brandi.kubala@cuanschutz.edu
      • Contact: Erin Schenk; Phone Number: 303-724-4304; Email: erin.schenk@cuanschutz.edu
      • Principal Investigator: Erin Schenk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects who have a diagnosis of State IV Lung Adenocarcinoma with EGFR activating mutation

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
gene expression changes	change from baseline of tumor gene expression profile at 2 weeks. Global gene expression data will be collected using RNAseq	baseline and 2 weeks (+/- 1 week) for each patient.
protein expression change	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)	baseline and 2 weeks (+/- 1 week) for each patient.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depth of Response	Correlation between the depths of tumor response (by RECIST v1.1) (percentage decrease in tumor size) with the presence of an EMT signature.	Study startup through 36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Adverse Events	Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0	Study startup through 36 months
Success rate of Repeat Biopsy	Success rate of early rebiopsy in obtaining tumor samples that have evaluable material for RNA Seq and other analyses	Study startup through 36 months
Progression Free Survival	Length of PFS as per RECIST 1.1	Study startup through 36 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Erin Schenk, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2016
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: January 30, 2017
• First Submitted That Met QC Criteria: February 1, 2017
• First Posted (Estimated): February 3, 2017

Study Record Updates

• Last Update Posted (Estimated): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 15-2316.cc

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No