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

Recruiting

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

• Registration Number: NCT03042221
• Lead Sponsor: University of Colorado, Denver

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-05-10
• Study First Submitted: 2017-01-30
• Study First Submitted QC: 2017-02-01
• Study First Posted: 2017-02-03
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-05
• Last Update Posted: 2025-02-06
• Primary Completion: 2026-11-01
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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)
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

Secondary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

University of Colorado, Cancer Center; 🇺🇸 Aurora, Colorado, United States