Identifying tumor survival mechanisms in lung cancer after targeted therapy

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

This study is trying to see how lung cancer tumors change before and after treatment with a specific drug to find ways to make the treatment work better.

Quick facts

• Study type: Observational
• Enrollment: 100 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: University of Colorado, Denver (Academic / other)
• Drugs / interventions: chemotherapy, Immunotherapy, radiation
• Locations: 1 site (Aurora, Colorado)
• Trial ID: NCT03042221 on ClinicalTrials.gov

What this trial studies

This observational study aims to compare the characteristics of tumors in patients with oncogene-driven non-small cell lung cancer (NSCLC) before and after early treatment with Tyrosine Kinase Inhibitors (TKIs). By analyzing tumor biopsies and blood samples, researchers hope to identify early adaptive mechanisms that allow cancer cells to survive despite targeted therapy. This information could lead to the development of new treatment strategies that target these survival pathways, potentially improving patient outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with stage IV NSCLC harboring specific oncogene mutations and who have not received prior systemic therapy.

Not a fit: Patients with early-stage lung cancer or those who have already undergone systemic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more effective treatment strategies for patients with advanced lung cancer by targeting resistance mechanisms early.

How similar studies have performed: Other studies have shown promise in identifying resistance mechanisms in cancer therapies, suggesting that this approach could yield valuable insights.

Eligibility criteria

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.

Where this trial is running

Aurora, Colorado

• University of Colorado, Cancer Center — Aurora, Colorado, United States (Recruiting)

Study contacts

• Principal investigator: Erin Schenk — University of Colorado, Denver
• Study coordinator: Brandi Kubala

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