Carcinoma, Non-Small-Cell LungNCT02554591
Genomic Landscape of Ceritinib
An observational study of Carcinoma, Non-Small-Cell Lung and Non-small Lung Cancer, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The investigators propose to conduct a retrospective study of single agent ceritinib in patients with previously untreated anaplastic lymphoma kinase (ALK) rearranged adenocarcinoma of the lung with the sole purpose of characterizing the genomic landscape before ceritinib and at the time of disease progression. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung, Non-small Lung Cancer, Non-Small Cell Lung Cancer
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Sep 2015to 28 Feb 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Participants will be selected from the Washington University School of Medicine and Barnes-Jewish healthcare system who previously consented to study HRPO (Human Research Protection Office)# 201305031 ("Tissue and Blood Acquisition for Genomic Analysis and Collection of Health Information from Patients with Thoracic Malignancies, Suspected Thoracic Malignancies, or Mesothelioma").
Who may be able to join
- Diagnosis of metastatic stage IIIB/IV lung adenocarcinoma.
- Presence of known ALK gene rearrangement.
- Consented to HRPO# 201305031 ("Tissue and Blood Acquisition for Genomic Analysis and Collection of Health Information from Patients with Thoracic Malignancies, Suspected Thoracic Malignancies, or Mesothelioma") with an existing specimen prior to initiation of treatment with ceritinib.
- At least 18 years of age.
- Received treatment with standard of care ceritinib
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Retrospective Analysis of Genomic Landscape of ALK Positive NSCLC Prior to Ceritinib, and at Disease Progression Following Ceritinib
The investigators propose to conduct a retrospective study of single agent ceritinib in patients with previously untreated anaplastic lymphoma kinase (ALK) rearranged adenocarcinoma of the lung with the sole purpose of characterizing the genomic landscape before ceritinib and at the time of disease progression.
Read the detailed description
Further improvements in therapy can only be achieved with a better understanding of the genomic landscape of ALK rearranged non-small cell lung cancer (NSCLC), specifically at the time of disease progression following treatment with ALK inhibitors. Recently, secondary ALK mutations, L1196M and G1269A have been described in patients with acquired resistance to crizotinib. A small subset of ALK positive lung cancer patients who progressed after treatment with ceritinib had tumors available for molecular analysis. Secondary mutations found included G1202R, F1174C, and F1174V. While this is interesting, an unbiased genomic study (exome or whole genome sequencing) using massively parallel sequencing at the time of disease progression is critical to fully understand the clonal evolution and the molecular mechanisms underpinning treatment resistance. To the best of the investigators' knowledge, such a study has not yet been reported.
The investigators believe the time is ripe now to comprehensively characterize genomic alterations using massively parallel sequencing technology of ALK driven adenocarcinoma of the lung to fully understand the clonal heterogeneity before therapy and fully understand the clonal evolution and the molecular mechanisms underpinning treatment resistance. A better understanding of genomic alterations through an unbiased comprehensive approach likely would lead to rationally designed therapy to augment response to ALK inhibitors.
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What is being measured
The primary outcome is the main question the study is designed to answer.
Genetic changes associated with disease progression following treatment with ceritinib
- The investigators will compare tumor sequencing prior to ceritinib treatment to the time of disease progression to see if the genetic sequencing changed between pre-treatment and progression.
- The investigators plan to conduct exome and transcriptome sequencing of tumor before therapy with certitinib and at the time of relapse. In addition, exome sequencing of peripheral blood DNA will be done (for germline). Given the complexities of genomic analyses of paired samples in the face of limited data, the investigators will not be able to do any formal power calculations in this feasibility study.
- Disease progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Measured: Estimated to be 1 year
Secondary outcomes (2)
Types of mutations in signaling kinases associated with therapeutic response
- Investigators will look at tumor tissue associated with a therapeutic response and compare with tumor tissue associated with disease progression and see if there are any mutation differences.
- Therapeutic Response
- Complete response is disappearance of all target lesions and non-target lesions.
- Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Measured: Estimated to be 1 year
Allelic ratio of wild type ALT to ALK gene rearrangement (roughly corrected for intrinsic difference in tumor cellularity) with duration of response
- A variant is considered to have mutant biased expression if the variant is expressed and the variant allele frequency is greater than 20% higher in the RNA-seq data compared to the exome sequencing data. A variant is considered to have wild type biased expression if the gene is expressed, the region of the variant is covered at 5X or greater depth, and the VAF is at least 20% lower in the RNA-seq data compared to the exome sequencing data.
- Duration of response is the duration of overall response is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Measured: Estimated to be 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2015 (estimated)
- Study start16 Sep 2015
- Primary completion28 Feb 2018
- Study completion28 Feb 2018
Why it stopped: Changes in treatment plans affecting drug therapy choices
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Ramaswamy Govindan, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02554591
- Sponsor's protocol ID
- 201509030
- Status last verified
- Mar 2018
- First submitted
- 8 Sep 2015
- Last updated
- 5 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Retrospective Analysis of Genomic Landscape of ALK Positive NSCLC Prior to Ceritinib, and at Disease Progression Following Ceritinib
- ClinicalTrials.gov ID
- NCT02554591
- Acronym / sponsor ID
- 201509030
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Changes in treatment plans affecting drug therapy choices
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- 16 Sep 2015 (actual)
- Primary completion
- 28 Feb 2018 (actual)
- Study completion
- 28 Feb 2018 (actual)
- First posted
- 18 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators propose to conduct a retrospective study of single agent ceritinib in patients with previously untreated anaplastic lymphoma kinase (ALK) rearranged adenocarcinoma of the lung with the sole purpose of characterizing the genomic landscape before ceritinib and at the time of disease progression.
Detailed description
Further improvements in therapy can only be achieved with a better understanding of the genomic landscape of ALK rearranged non-small cell lung cancer (NSCLC), specifically at the time of disease progression following treatment with ALK inhibitors. Recently, secondary ALK mutations, L1196M and G1269A have been described in patients with acquired resistance to crizotinib. A small subset of ALK positive lung cancer patients who progressed after treatment with ceritinib had tumors available for molecular analysis. Secondary mutations found included G1202R, F1174C, and F1174V. While this is interesting, an unbiased genomic study (exome or whole genome sequencing) using massively parallel sequencing at the time of disease progression is critical to fully understand the clonal evolution and the molecular mechanisms underpinning treatment resistance. To the best of the investigators' knowledge, such a study has not yet been reported.
The investigators believe the time is ripe now to comprehensively characterize genomic alterations using massively parallel sequencing technology of ALK driven adenocarcinoma of the lung to fully understand the clonal heterogeneity before therapy and fully understand the clonal evolution and the molecular mechanisms underpinning treatment resistance. A better understanding of genomic alterations through an unbiased comprehensive approach likely would lead to rationally designed therapy to augment response to ALK inhibitors.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Participants will be selected from the Washington University School of Medicine and Barnes-Jewish healthcare system who previously consented to study HRPO (Human Research Protection Office)# 201305031 ("Tissue and Blood Acquisition for Genomic Analysis and Collection of Health Information from Patients with Thoracic Malignancies, Suspected Thoracic Malignancies, or Mesothelioma").
Key inclusion criteria (5 listed)
- Diagnosis of metastatic stage IIIB/IV lung adenocarcinoma.
- Presence of known ALK gene rearrangement.
- Consented to HRPO# 201305031 ("Tissue and Blood Acquisition for Genomic Analysis and Collection of Health Information from Patients with Thoracic Malignancies, Suspected Thoracic Malignancies, or Mesothelioma") with an existing specimen prior to initiation of treatment with ceritinib.
- At least 18 years of age.
- Received treatment with standard of care ceritinib
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Genetic changes associated with disease progression following treatment with ceritinib
Time frame: Estimated to be 1 year
* The investigators will compare tumor sequencing prior to ceritinib treatment to the time of disease progression to see if the genetic sequencing changed between pre-treatment and progression. * The investigators plan to conduct exome and transcriptome sequencing of tumor before therapy with certitinib and at the time of relapse. In addition, exome sequencing of peripheral blood DNA will be done (for germline). Given the complexities of genomic analyses of paired samples in the face of limited data, the investigators will not be able to do any formal power calculations in this feasibility study. * Disease progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
2 secondary outcomes
Types of mutations in signaling kinases associated with therapeutic response
Time frame: Estimated to be 1 year
Allelic ratio of wild type ALT to ALK gene rearrangement (roughly corrected for intrinsic difference in tumor cellularity) with duration of response
Time frame: Estimated to be 1 year
Results and safety
The study was stopped early (reason given: Changes in treatment plans affecting drug therapy choices). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2018.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ramaswamy Govindan, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Carcinoma, Non-Small-Cell Lung and Non-small Lung Cancer, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Changes in treatment plans affecting drug therapy choices). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Genetic changes associated with disease progression following treatment with ceritinib (time frame: Estimated to be 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2018.