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

Non-Small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03042221
• Other study ID #: 15-2316.cc
• Status: Recruiting
• Start date: May 10, 2016
• Est. completion date: September 30, 2027

Study information

• Verified date: January 2024
• Source: University of Colorado, Denver
• Contact: Brandi Kubala
• Phone: 303-724-1657
• Email: brandi.kubala[@]cuanschutz.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: September 30, 2027
• Est. primary completion date: November 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Locations

Country	Name	City	State
United States	University of Colorado, Cancer Center	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Evaluation of Adverse Events	Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0	Study startup through 36 months
Other	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
Other	Progression Free Survival	Length of PFS as per RECIST 1.1	Study startup through 36 months
Primary	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.
Primary	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	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