Clinical trial NCT04087473: Plasma Molecular Profiling in ALK Inhibitor Resistant NSCLC
Official title: Plasma Molecular Profiling in ALK Inhibitor Resistant Non-Small Cell Lung Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Non-small Cell Lung Cancer
ALK-Positive Lung Cancer
Keywords: ALK inhibitor (ALKi)
NSCLC
Anaplastic lymphoma kinase (ALK) fusion oncogene NSCLC
Guardant360 assay
Next-Generation Sequencing (NGS) DNA sequencing test
Cell-free circulating tumor DNA (ctDNA)
Plasma profiling
Blood-based assay
Mutational testing
74 genetic alterations (point mutations, copy number variants, fusions, insertions, deletions)
ALK resistance mutations
Lead sponsor: National Cancer Centre, Singapore
Sponsor class: OTHER
Collaborators: name: Guardant Health AMEA, Inc.
First posted: 2019-09-12
Enrollment: 50
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Two cohorts will be enrolled, the first cohort will consist of patients that have received prior 2nd generation ALKi only, and the second cohort with patients that have received prior 1st and 2nd generation ALKi.

Brief summary: The investigators plan to understand a comprehensive molecular profiling via the plasma, with the primary aim of using this form on analysis to guide subsequent treatment selection. This study will provide a better understanding of ALK resistance in the treatment of Asian lung cancers and allow for improved clinical outcomes by 'matching' the secondary mutations to an ALK inhibitor which would allow for the greatest coverage ultimately leading to lasting duration of response.


Eligibility criteria: Inclusion Criteria:

* Patients with advanced ALK fusion oncogene positive lung adenocarcinoma that have progressed after 1-2 ALK inhibitors, with at least one prior line of 2nd generation ALKi (i.e. Ceritinib, Alectinib, Brigatinib or Ensartinib)
* The availability of sufficient plasma
* Age ≥ 21 years
* WHO performance status ≤ 2
* Life expectancy of ≥ 21 weeks
* Patients should have adequate organ function for potential consideration into clinical trials (routine blood tests are valid within 14 days before enrollment):

  1. Adequate bone marrow function as shown by: ANC ≥ 1.0x10\^9/L, Platelets ≥ 75x10\^9/L, Hb ≥ 7.5 g/dL
  2. Alanine aminotransferase (ALT) and aspirate aminotransferase (AST) normal range (or ≤ 3.0xULN if liver metastases are present)
* Willing to provide signed informed consent
* Patients whom do not fulfill the above criteria may be discussed on a case-by-case basis within the study team, for potential enrolment

Exclusion Criteria:

* Received more than 2 prior ALK inhibitors (ALKi)
* Symptomatic or uncontrolled brain metastases requiring concurrent treatment inclusive but not limited to surgery and radiation. Stable/ tailing doses of corticosteroids is permitted

Primary outcomes:
measure: Molecular profiling of plasma
timeFrame: 2 to 4 weeks after collection of plasma
Secondary outcomes:
measure: Patient survival status
timeFrame: After molecular profiling has been completed, every few months up to 2 years
measure: Subsequent patient treatment status
timeFrame: After molecular profiling has been completed, every few months up to 2 years
measure: Clinical outcomes of the subsequent treatments the patients receive
timeFrame: After molecular profiling has been completed, every few months up to 2 years
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: The Chinese University of Hong Kong
city: Seoul
country: Korea, Republic of
facility: Asan Medical Centre
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Singapore
country: Singapore
facility: National Cancer Center Singapore
Study officials:
affiliation: National Cancer Centre of Singapore
name: Daniel SW Tan, BSc, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
References: