Clinical trial NCT05116618: Detection of Resistance Mechanisms in Cerebrospinal Fluid for EGFR-mutant, ALK- and ROS1-rearranged
Official title: Detection of Resistance Mechanisms in Cerebrospinal Fluid for EGFR-mutant, ALK- and ROS1-rearranged Non-small Cell Lung Cancer Patients With Central Nervous System (CNS) Progression After Evidence of Prior CNS Benefit on Relevant Tyrosine Kinase Inhibitors
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Non-Small Cell Lung Cancer
Keywords: Progression
Central Nervous System
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: Inivata
First posted: 2021-11-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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

Detailed description: 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

* 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)

Eligibility criteria: Inclusion Criteria:

1. Provision to sign and date the consent form
2. Stated willingness to comply with all study procedures and be available for the duration of the study.
3. Be aged 18 or older.
4. 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
5. Stage IV NSCLC disease according to AJCC 8th edition
6. 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
7. 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
8. Prior CNS radiation therapy is allowed

Exclusion Criteria:

1. 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
2. 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
3. Women who are documented as pregnant or breastfeeding

Primary outcomes:
measure: 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
timeFrame: 3 years
Secondary outcomes:
measure: Compare and contrast mechanisms of resistance in CNS progression versus eCNS progression
timeFrame: 3 years
Other outcomes:
measure: Determine the clinical outcomes of subsequent lines of therapy base on CNS data from this study
timeFrame: 3 years
measure: Determine the clinical outcomes of subsequent lines of therapy base on CNS data from this study
timeFrame: 3 years
measure: Determine the clinical outcomes of subsequent lines of therapy base on eCNS data from this study
timeFrame: 3 years
measure: Determine the clinical outcomes of subsequent lines of therapy base on eCNS data from this study
timeFrame: 3 years
measure: Determine the safety of CSF sampling for detection of resistance mechanisms in the context of CNS progression
timeFrame: 3 years
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: Colorado Research Center
state: Colorado
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
Study officials:
affiliation: Colorado Research Center
name: Ross Camidge
role: PRINCIPAL_INVESTIGATOR
References: