Study of Plasma NGS for Assessment, Characterization, Evaluation of Patients With ALK Resistance
| Status: | Recruiting |
|---|---|
| Conditions: | Lung Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/9/2019 |
| Start Date: | January 23, 2019 |
| End Date: | February 23, 2021 |
| Contact: | Marissa Lawrence, BS |
| Email: | SPACEWALK@dfci.harvard.edu |
| Phone: | 617-632-6455 |
ALCMI-011: Study of Plasma Next Generation Sequencing for Assessment, Characterization, Evaluation of Patients With ALK Resistance (SPACEWALK)
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.
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.
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.
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.
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
We found this trial at
1
site
450 Brookline Ave
Boston, Massachusetts 2215
Boston, Massachusetts 2215
617-632-3000
Principal Investigator: Geoffrey R Oxnard, MD
Phone: 617-632-6455
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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