Study of Plasma NGS for Assessment, Characterization, Evaluation of Patients With ALK Resistance

NCT03833934 | Completed Results

• 2 other identifiers: ALCMI-0115R21CA234816
• Study Type: observational
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

ALK-positive lung cancer is a subtype of lung cancer which carries a change in a gene called ALK (anaplastic lymphoma kinase). There are now many drugs for patients with ALK-positive lung cancer that slow cancer growth. However, after some time, just as bacteria evolve resistance to antibiotics, ALK-positive lung cancers evolve ways to avoid the therapies by developing new mutations so the drugs lost their effectiveness. These new mutations can potentially be treated with a different drug. For these new therapies, the range of mutations that can develop at resistance is not well understood. It is now possible to detect the presence of mutations or changes in the genetic structure in lung cancer by analyzing a patient's blood for bits of material shed by tumor. This approach is often called a liquid biopsy. Recently, researchers have shown that looking at tumor molecules through liquid biopsies can provide doctors with some of the same information that tissue biopsies provide. For example, liquid biopsies can be used to detect mutations that cause drug resistance. Obtaining liquid biopsies on patients with ALK-positive lung cancers at resistance to therapy may help better understand the different mutations that develop and guide therapy decisions. In this research study, a blood specimen will be collected and submitted for liquid biopsy analysis at a commercial diagnostic company. This company specializes in analyzing tumor material found in blood. Specifically, it will look for genetic changes in the ALK gene that could help understand why a cancer has developed drug resistance. This research study is for lung cancer patients with ALK-positive lung cancer who had been on a newer ALK targeted treatment (such as ceritinib, alectinib, brigatinib, or lorlatinib) to determine whether they have developed ALK resistance mutations. The investigators will collect a blood sample to examine these mutations. Participants will not have to have a tissue biopsy to participate in this study. Participants do not have to visit Dana-Farber Cancer Institute (DFCI) to participate. All study procedures will be performed remotely.

Conditions

Non-Small Cell Lung Cancer

Keywords

ALK positive

Outcome Measures

Primary Outcomes (6)

• Prevalence of ALK Fusion

  To determine the prevalence of the ALK gene fusion in the cohort of patients with ALK-positive NSCLC with progression

  32 months

• ALK Fusion Allelic Frequency

  To determine the relative percentage of the ALK fusion within the cohort's gene pool

  32 months

• Overall Prevalence of ALK Resistance Mechanism Among Patients With the ALK Fusion

  To determine the overall prevalence of ALK resistance mechanism in patients with detectable ALK fusion in plasma as determined per plasma NGS

  32 months

• Type of Resistance Mechanism: One or More Secondary ALK Kinase Domain Resistance Mutations

  To determine the prevalence of the various types of ALK resistance mechanisms as measured by NGS

  32 months

• Type of ALK Resistance Mechanism: Both ALK Resistance Mutations and Bypass Resistance

  To determine the prevalence of the various types of ALK resistance mechanisms as measured by NGS

  32 months

• Prevalance of ALK Restance Mechanism: Bypass Track Resistance

  To determine the prevalence of the various types of ALK resistance mechanisms as measured by NGS

  32 months

Secondary Outcomes (2)

• Changed Treatment for NSCLC

  32 months

• Treatment Outcome: >50% Reduction of ALK Fusion Allelle Frequency

  32 months

Study Arms (1)

ALK-positive NSCLC with progression

Patients in this group signed consent, met eligibility criteria, and all had ALK-positive cancer of a primary lung lesion with systemic progression (excluding the central nervous system)

Eligibility Criteria

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

Study Population

This research study is for lung cancer patients with ALK-positive lung cancer who had been on a newer ALK targeted treatment (such as ceritinib, alectinib, brigatinib, or larlatinib).

You may qualify if:

• Men or women older than 18 years at the time of consent.
• Demonstration of having advanced ALK positive NSCLC.
• Systemic progression (not CNS only progression) within the past 30 days while receiving a next generation ALK TKI.
• Patient must not have started a new line of therapy before signing the informed consent form.
• Willingness to provide a blood specimen prior to the initiation of a new line of treatment.
• Willing to provide clinical and medical information to the study team as required.
• Ability to read, write and communicate in English.
• Ability to sign a web-based informed consent form.

You may not qualify if:

• Participants who are unable to provide informed consent.
• Participants who are 18 years of age or younger.
• Participants who are unable to comply with the study procedures.
• Known existence of an uncontrolled intercurrent illness including, but not limited to, psychiatric illness or social situations that would impair compliance with study requirements.
• Participants who have previously enrolled to the study

Sponsors & Collaborators

• Addario Lung Cancer Medical Institute: lead
• Dana-Farber Cancer Institute: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Lawrence MN, Tamen RM, Martinez P, Sable-Hunt A, Addario T, Barbour P, Shaffer T, Hosseini SA, Bertucci C, Lim LP, Hong F, Michael K, Simon GR, Riess JW, Awad MM, Oxnard GR. SPACEWALK: A Remote Participation Study of ALK Resistance Leveraging Plasma Cell-Free DNA Genotyping. JTO Clin Res Rep. 2021 Feb 3;2(4):100151. doi: 10.1016/j.jtocrr.2021.100151. eCollection 2021 Apr.

  PMID: 34590008 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Blood specimens will be tested for genetic mutations in ALK and other genes that may be important for lung cancer. The participant and their doctor will receive a copy of the test results. The test results will describe the gene alterations that are detected in the blood sample. The assay covers a region of the ALK gene and other lung cancer genes where resistance alterations can occur.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Ericka Izzo, Clinical Project Manager
• Organization: Addario Lung Cancer Medical Institute (ALCMI)

eizzo@alcmi.org

941-713-1225

Study Officials

• Geoffrey R Oxnard, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: February 7, 2019
• Study Start: January 23, 2019
• Primary Completion: October 31, 2023
• Study Completion: October 31, 2023
• Last Updated: October 2, 2025
• Results First Posted: October 2, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)