Detection of Resistance Mechanisms in Cerebrospinal Fluid for EGFR-mutant, ALK- and ROS1-rearranged

NCT05116618 | Withdrawn DMC

• 1 other identifier: 20-1193.cc
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

To determine the detection rate of driver oncogenes and resistance mechanisms in cerebrospinal fluid (CSF) for patients with CNS progression (with or without extra-CNS (eCNS) progression) and concordance with plasma/tissue

Conditions

Non-Small Cell Lung Cancer

Keywords

Progression; Central Nervous System

Outcome Measures

Primary Outcomes (1)

• Determine the detection rate of driver oncogenes and resistance mechanisms in cerebrospinal fluid (CSF) for patients with CNS progression (with or without extra-CNS (eCNS) progression) and concordance with plasma/tissue

  * For each individual patient with CNS progression (with or without eCNS progression), compare the molecular status (primary oncogene detection and any mechanisms of identifiable resistance including EGFR-, ALK- and ROS1-mutations, ALK-amplification and bypass-tracks activating mutations) of CSF, plasma and CNS tissue (if data from pathology report is available) * Molecular status will also be compared with previously obtained and stored plasma/tissue prior to the initiation of current next-generation tyrosine-kinase inhibitor (TKI)

  3 years

Secondary Outcomes (1)

• Compare and contrast mechanisms of resistance in CNS progression versus eCNS progression

  3 years

Other Outcomes (5)

• Determine the clinical outcomes of subsequent lines of therapy base on CNS data from this study

  3 years

• Determine the clinical outcomes of subsequent lines of therapy base on CNS data from this study

  3 years

• Determine the clinical outcomes of subsequent lines of therapy base on eCNS data from this study

  3 years

Study Arms (3)

Cohort 1

10 evaluable enrollments to Cohort 1 with EGFR-mutant NSCLC

Diagnostic Test: InVisionFirst-Lung ctDNA assay

Cohort 2

10 evaluable enrollments to Cohort 2 with ALK-rearranged NSCLC

Diagnostic Test: InVisionFirst-Lung ctDNA assay

Cohort 3

10 evaluable enrollments to Cohort 3 with ROS1-rearranged NSCLC

Diagnostic Test: InVisionFirst-Lung ctDNA assay

Interventions

InVisionFirst-Lung ctDNA assay DIAGNOSTIC_TEST

An enhanced tagged/targeted-amplicon sequencing technology for detection of genomic alterations in 36 commonly mutated genes in plasma ctDNA with a sensitivity of 73.9% and specificity of 99.8%.

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with stage IV EGFR, ALK, or ROS1-mutant NSCLC who had CNS progression after at least 6 months of stable CNS disease on a relevant TKI are screened. Patients must meet all Inclusion/Exclusion Criteria to participate in the study.

You may qualify if:

• Provision to sign and date the consent form
• Stated willingness to comply with all study procedures and be available for the duration of the study.
• Be aged 18 or older.
• Pathologically confirmed NSCLC with EGFR-mutation, or ALK- or ROS1-rearrangement and currently on an EGFR, or ALK or ROS1 tyrosine-kinase inhibitor (TKI) as applicable
• Stage IV NSCLC disease according to AJCC 8th edition
• Known CNS metastasis prior to current line of therapy with CR/PR/SD for at least 6 months (not purely attributable to prior local therapy such as radiation) on current EGFR, or ALK or ROS1 TKI, confirmed by at least one of the following modalities:
• CT/MRI for brain metastases
• characteristic signs and/or symptoms indicating progression,
• cytology,
• imaging findings for leptomeningeal disease
• Confirmed current CNS progression, with or without eCNS progression, on the same TKI based on at least one of the following modalities:
• CT/MRI for brain metastases
• characteristic signs and/or symptoms indicating progression,
• cytology,
• imaging findings for leptomeningeal disease

You may not qualify if:

• Has contraindications to receive a lumbar puncture which may include, but are not limited to the following, at the discretion of the patient's oncologist or physician performing the LP:
• Clinical and/or radiographic evidence of mass effect of raised intracranial pressure (ICP) with risk for cerebral herniation
• Thrombocytopenia (defined as platelet count ≤ 50 or per local guidelines) or other bleeding diathesis
• Currently on antiplatelet or anticoagulant therapy at time of consent, for which the thrombosis risk of holding for LP is deemed unacceptable
• Suspected spinal epidural abscess
• Any other condition determined by the clinician to be a contraindication
• History of a second primary malignancy (including a second primary lung cancer) with the exceptions for:
• Malignancy treated with curative intent and with no known active disease ≥5 years, and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease
• Women who are documented as pregnant or breastfeeding

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Inivata: collaborator

Study Sites (3)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Colorado Research Center

Aurora, Colorado, 80045, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Disease Progression

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ross Camidge

  Colorado Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2021
• First Posted: November 11, 2021
• Study Start: January 6, 2022
• Primary Completion: September 15, 2022
• Study Completion: September 15, 2022
• Last Updated: September 21, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)