Clinical trial NCT03042221: Early Rebiopsy to Identify Biomarkers of Tumor Cell Survival Following EGFR, ALK, ROS1 or BRAF TKI Therapy
Official title: Early Rebiopsy to Identify Mechanisms and Biomarkers of Tumor Cell Survival Following Systemic Therapy for Lung Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2017-02-03
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects who have a diagnosis of State IV Lung Adenocarcinoma with EGFR activating mutation

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.


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.

Primary outcomes:
measure: gene expression changes
timeFrame: baseline and 2 weeks (+/- 1 week) for each patient.
measure: protein expression change
timeFrame: baseline and 2 weeks (+/- 1 week) for each patient.
Secondary outcomes:
measure: Depth of Response
timeFrame: Study startup through 36 months
Other outcomes:
measure: Evaluation of Adverse Events
timeFrame: Study startup through 36 months
measure: Success rate of Repeat Biopsy
timeFrame: Study startup through 36 months
measure: Progression Free Survival
timeFrame: Study startup through 36 months
Locations:
city: Aurora
country: United States
facility: University of Colorado, Cancer Center
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Erin Schenk
role: PRINCIPAL_INVESTIGATOR
References: