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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03833934
Recruitment Status : Recruiting
First Posted : February 7, 2019
Last Update Posted : February 7, 2019
Dana-Farber Cancer Institute
Information provided by (Responsible Party):
Addario Lung Cancer Medical Institute

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.

Condition or disease Intervention/treatment
Non-Small Cell Lung Cancer Diagnostic Test: Plasma Next Generation Sequencing (NGS)

Detailed Description:

SPACEWALK is an innovative remote consent and participation study using next-generation sequencing (NGS) of plasma cell-free DNA (cfDNA) to characterize resistance mechanisms arising in ALK-positive non-small cell lung cancer (NSCLC) after progression while on a next generation ALK tyrosine kinase inhibitor (TKI). Additionally, the study will capture the potential of genomic-driven resistance therapy approach for effecting outcomes in patients with advanced ALK-positive NSCLC and TKI resistance. Finally, the study will assess the role of repeat plasma NGS in evaluating drug response.

The study will accrue patients with advanced ALK-positive NSCLC on systemic progression (outside the brain) while on treatment with a next-generation ALK TKI. Any patient interested in the study will find information about the study on the study website. The patient will consent remotely through the study website and documentation of advanced ALK-positive NSCLC and systemic progression while on a next-generation ALK TKI. The study team will then reach out to the patient to confirm eligibility and send a blood collection kit. In the study kit the study participants will find all the necessary materials for local blood draws and collected specimens will be sent directly to the central study laboratory (Resolution Bioscience) for plasma NGS.

Plasma NGS of cfDNA will involve sequencing of 19 genes, including ALK, permitting remote tumor genotyping. Plasma NGS analysis and results will be done following standard procedures of the Resolution Bioscience CLIA-certified laboratory. Results will take 1-2 weeks to be sent back to study participants, their physicians and study team. Those plasma NGS reports will not include any specific treatment recommendations but will describe the presence of an ALK rearrangement, ALK resistance mutation, or other relevant mutations.

Study participants are then followed remotely. The study coordinator will contact the participants weekly for 4 weeks after enrolled into the study to learn of any new treatment initiation and to release an additional plasma collection kit 2-4 weeks after starting treatment. Study participants will then be remotely contacted every 3 months to follow clinical outcomes on therapy for up to 2 years. If the cancer begins to grow again on the participant's new treatment, the patient will have the option to provide a third blood specimen. Medical records and local imaging will be collected and studied.

The primary objective of the study is to characterize ALK TKI resistance to next-generation ALK TKIs in patients with advanced ALK-positive NSCLC. Secondarily, the investigators will assess the potential of plasma NGS to impact outcome on treatment by studying time to treatment discontinuation (TTD). Serial plasma NGS will also be assessed as a response biomarker. A total of 300 patients will be enrolled, with the expectation that approximately 200 will have tumor-related mutations detected in plasma NGS.

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Study Type : Observational
Estimated Enrollment : 300 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: ALCMI-011: Study of Plasma Next Generation Sequencing for Assessment, Characterization, Evaluation of Patients With ALK Resistance (SPACEWALK)
Actual Study Start Date : January 23, 2019
Estimated Primary Completion Date : August 23, 2020
Estimated Study Completion Date : February 23, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Group/Cohort Intervention/treatment
Plasma Next Generation Sequencing (NGS)
Subjects will be sent blood collection kits with the necessary materials for local draws and those specimens will be sent directly by the subjects to the central laboratory (Resolution Bioscience) for plasma NGS. Plasma NGS results will be returned to the subject, their treating physician and study team, aiming to return results within 2 weeks by Resolution Bioscience.
Diagnostic Test: Plasma Next Generation Sequencing (NGS)
Liquid biospys

Primary Outcome Measures :
  1. Prevalence of ALK resistance mutations after different ALK targeted therapies [ Time Frame: 32 months ]
    To study the relationship between specific ALK resistance mutations measured through plasma NGS and a specific next gneration ALK TKI received before progression and/or the number of ALK TKIs received

Secondary Outcome Measures :
  1. Sensitivity of plasma NGS for ALK TKI resistance [ Time Frame: 32 months ]
    To study the feasibility, sensitivity, and turnaround time of plasma NGS in lung cancer patients with ALK TKI resistance.

  2. Time until treatment discontinuation on subsequent therapy [ Time Frame: 32 months ]
    To study the survival data of patients with ALK TKI resistance mechanism detected and subsequent therapy received.

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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03833934

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Contact: Marissa Lawrence, BS 617-632-6455
Contact: Geoffrey R Oxnard, MD

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United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Marissa Lawrence, BS    617-632-6455   
Principal Investigator: Geoffrey R Oxnard, MD         
Sponsors and Collaborators
Addario Lung Cancer Medical Institute
Dana-Farber Cancer Institute
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Principal Investigator: Geoffrey R Oxnard, MD Dana-Farber Cancer Institute

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Responsible Party: Addario Lung Cancer Medical Institute Identifier: NCT03833934     History of Changes
Other Study ID Numbers: ALCMI-011
First Posted: February 7, 2019    Key Record Dates
Last Update Posted: February 7, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Addario Lung Cancer Medical Institute:
ALK positive
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases