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

Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05116618
• Other study ID #: 20-1193.cc
• Status: Withdrawn
• Start date: January 6, 2022
• Est. completion date: September 15, 2022

Study information

• Verified date: September 2022
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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)

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 15, 2022
• Est. primary completion date: September 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Diagnostic Test:
• InVisionFirst-Lung ctDNA assay
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%.

Locations

Country	Name	City	State
United States	Colorado Research Center	Aurora	Colorado
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	Georgetown University	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	Inivata

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Determine the clinical outcomes of subsequent lines of therapy base on CNS data from this study	ORR in CNS	3 years
Other	Determine the clinical outcomes of subsequent lines of therapy base on CNS data from this study	PFS in CNS	3 years
Other	Determine the clinical outcomes of subsequent lines of therapy base on eCNS data from this study	ORR in eCNS	3 years
Other	Determine the clinical outcomes of subsequent lines of therapy base on eCNS data from this study	PFS in eCNS	3 years
Other	Determine the safety of CSF sampling for detection of resistance mechanisms in the context of CNS progression	AEs associated with procedure	3 years
Primary	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	Compare and contrast mechanisms of resistance in CNS progression versus eCNS progression	For patients with both CNS and eCNS progression, compare distribution of resistance mechanisms between CSF, plasma, CNS tissue (if data from pathology report is available) and tissue from site of eCNS progression (if data from pathology report is available); Compare distribution of resistance mechanisms in CSF for all patients with CNS progression (with or without eCNS progression) to historical data of distribution of resistance mechanisms to next-generation TKI from ctDNA/tumor tissue samples	3 years