Non Small Cell Lung CancerNCT02055144
Veristrat as Predictor of Benefit of First Line Non Small Cell Lung Cancer (NSCLC) Patients From Standard Chemotherapy
An observational study of Non Small Cell Lung Cancer, run by IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy at 1 site in Italy.
Trial summary
VeriStrat® is a pretreatment blood-based test correlated with clinical outcome after EGFR-TKI therapy in non-small cell lung cancer (NSCLC) patients. The investigators hypothesis is that VeriStrat could be also employed as a biomarker of benefit from treatment with standard chemotherapy regimens in first line NSCLC… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- Feb 2011to Mar 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: Patients affected by advanced non small cell lung cancer who are chemotherapy-naive and candidates for first-line chemotherapy. This population includes patients with non-squamous histology and patients with squamous histology.
Who may be able to join
- Histologically or cytologically documented inoperable, locally advanced (stage IIIb with supraclavicular lymph node metastases),metastatic (stage IV) or recurrent NSCLC
- Age ≥18 years
- Life expectancy more than 3 months
- ECOG performance status 0-1
- At least one unidimensionally measurable lesion (as per RECIST criteria ver 1.1)
- Adequate baseline bone marrow, hepatic and renal function
Show all 9Show fewer
- Patients may have had prior therapy providing the following conditions are met:
- Radiation therapy: wash-out period of 28 days; Surgery: wash-out period of 14 days
- Patients must give written informed consent to participate in the study
Who cannot join
- Prior chemotherapy or treatment with another systemic anti-cancer agent (for example tyrosine kinase inhibitor).
- Patients must not receive any other investigational agents while on study
- Patients with myocardial infarction within the last six (6) months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
- History or evidence upon physical examination of CNS disease unless adequately treated (e.g., any brain metastasis, seizure not controlled with standard medical therapy, or history of stroke).
- Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol
- Pregnancy or lactation. Patients - both males and females - with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration
Trial locations and contacts
1 site in 1 country.
Francesco Grossi, MD contact
Italy1 site, 1 recruiting
- Recruiting
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro
Genoa, 16132
Francesco Grossi, MD, +393355255484, fg1965@libero.it
About this study
Official title: An Exploratory Study of the Performance of Mass-Spectrometry Based Test Veristrat in Prediction of Benefit of First Line NSCLC Patients From Treatment With Standard Chemotherapy Regimens
VeriStrat® is a pretreatment blood-based test correlated with clinical outcome after EGFR-TKI therapy in non-small cell lung cancer (NSCLC) patients.
The investigators hypothesis is that VeriStrat could be also employed as a biomarker of benefit from treatment with standard chemotherapy regimens in first line NSCLC patients.
Read the detailed description
VeriStrat®, a pretreatment blood-based test correlated with clinical outcome after EGFR-TKI therapy in non-small cell lung cancer (NSCLC) patients, was developed and validated in a multi-institutional study of advanced NSCLC patients treated with gefitinib [Taguchi et al] . The VeriStrat algorithm was developed using a training set of pre-treatment serum samples from patients who then experienced either long term stable disease or early progression on gefitinib therapy. Mass spectra from these patients' serum samples were used to define eight MS features (i.e. peaks), differentiating these two outcome groups. An algorithm (VeriStrat) utilizing these features and based on a k-nearest neighbors (KNN) classification scheme was created and its parameters were optimized using additional spectra from the training cohort. All aspects of VeriStrat were frozen after development. VeriStrat assigns each spectrum a "Good" or "Poor" label. VeriStrat was validated in a blinded fashion on two independent cohorts of patients who were treated with gefitinib or erlotinib. These studies confirmed that patients classified as "Good" had better outcome than patients classified as "Poor" (HR of death = 0.47 P = 0.0094 in one cohort, HR of death = 0.33 P = 0.0007 in the other).
In the original study, VeriStrat was shown to correlate with clinical outcome following EGFR-TKI therapy, but not in the chemotherapy or post-surgery setting: No statistically significant difference was seen in the overall survival of patients classified as "Good" or "Poor" from the serum from patients collected before second-line chemotherapy (HR = 0.74, 95%, P = 0.42 in one cohort (cohort B) and HR = 0.81, P = 0.54 in another (cohort C)). In a third control cohort of patients with resected early-stage NSCLC, the hazard ratio for overall survival was 0.90 (P = 0.79). However, further analysis of the subsets of chemotherapy samples demonstrated that separation between "Good" and "Poor" arms may depend on a particular type of chemotherapy. Thus a retrospective subset analysis of the cohort C showed that while patients treated with docetaxel in second line did not show any sign of separation, patients receiving a combination of platinum-based agents with either vinorelbine or gemcitabine or paclitaxel had a trend to separation between the two arms.
The working hypothesis for the mechanism is that the VeriStrat "Poor" label is related to the activation of canonical and non-canonical MAPK pathways downstream from receptor tyrosine kinases, with possible cross-talk activation of the NF-kB pathway. This means that VeriStrat may demonstrate different predictive performance depending on the particular chemotherapy treatment and its associated with cell pathway interactions.
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- NSCLC, VeriStrat, chemotherapy, circulating tumor cells
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplastic Cells, Circulating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Non squamous histology | patients with advanced, non-squamous non-small cell lung cancer treated with cisplatin (or carboplatin) and pemetrexed. Maintenance with pemetrexed is allowed. | |
| Squamous histology | patients with advanced squamous non-small cell lung cancer treated with cisplatin (or carboplatin) and gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
The primary objective of this study is to evaluate the potential role of VeriStrat test as a biomarker of benefit from treatment with standard chemotherapy regimens in first line NSCLC patients in terms of progression-free survival (PFS) (primary endpoint) in two populations: patients with non-squamous histology treated with cisplatin and pemetrexed, and patients with squamous histology treated with cisplatin and gemcitabine
Measured: 2 years
Secondary outcomes (6)
Overall survival
A secondary endpoint is to evaluate the role of VeriStrat as a biomarker of the secondary endpoints overall survival, in two groups of first line patients with non-small cell lung cancer (NSCLC), described above.
Measured: 2 years
Correlation with RECIST response
A secondary endpoint is to evaluate the possible correlation of VeriStrat classification with best RECIST responses.
Measured: Every 6 weeks
Correlation with known biomarkers
A secondary endpoint is to evaluate the possible correlation of VeriStrat classification with the available measurements of known biomarkers: the mutation statutes of EGFR, K-RAS, and ALK, and levels of ERCC1, RRM1 and TS.
Measured: Every 6 weeks
Changes of VeriStrat with disease progression
A secondary endpoint is to evaluate possible changes of VeriStrat classification with disease progression.
Measured: Every 6 weeks
Metabolomics
A secondary endpoint is to identify, measure, and interpret the complex time-related concentrations, activity, and fluxes of endogenous metabolites in biosamples such as blood and urine to improve disease prognosis and monitoring; provide insight into drug metabolism and toxicology; provide a linkage between the human metabolome and the human genome and proteome.
Measured: Every 6 weeks
Circulating tumor cells.
A secondary endpoint is isolate, identify and characterize molecularly the circulating tumor cells (CTCs) before start of treatment (within 2 weeks), at each patient's evaluation and at progression.
Measured: Every 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2014 (estimated)
- Study startFeb 2011
- Primary completionJul 2017 (estimated)
- Study completionMar 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- 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
- Case only
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Francesco Grossi, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
- Investigators
- Francesco Grossi, MD, Principal investigator, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02055144
- Sponsor's protocol ID
- VERISTRAT/IST
- Status last verified
- Mar 2017
- First submitted
- 30 Jan 2014
- Last updated
- 7 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Morbelli S, Alama A, Ferrarazzo G, Coco S, Genova C, Rijavec E, Bongioanni F, Biello F, Dal Bello MG, Barletta G, Massollo M, Vanni I, Piva R, Nieri A, Bauckneht M, Sambuceti G, Grossi F. Circulating Tumor DNA Reflects Tumor Metabolism Rather Than Tumor Burden in Chemotherapy-Naive Patients with Advanced Non-Small Cell Lung Cancer: 18F-FDG PET/CT Study. J Nucl Med. 2017 Nov;58(11):1764-1769. doi: 10.2967/jnumed.117.193201. Epub 2017 Apr 27.
PubMed 28450567
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Study of the Performance of Mass-Spectrometry Based Test Veristrat in Prediction of Benefit of First Line NSCLC Patients From Treatment With Standard Chemotherapy Regimens
- ClinicalTrials.gov ID
- NCT02055144
- Acronym / sponsor ID
- VERISTRAT/IST
- Conditions
- Non Small Cell Lung Cancer
- Keywords
- NSCLC, VeriStrat, chemotherapy, circulating tumor cells
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, ItalyUniversity, hospital or other
- Study start
- Feb 2011
- Primary completion
- Jul 2017 (estimated)
- Study completion
- Mar 2018 (estimated)
- First posted
- 4 Feb 2014 (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.
VeriStrat® is a pretreatment blood-based test correlated with clinical outcome after EGFR-TKI therapy in non-small cell lung cancer (NSCLC) patients.
The investigators hypothesis is that VeriStrat could be also employed as a biomarker of benefit from treatment with standard chemotherapy regimens in first line NSCLC patients.
Detailed description
VeriStrat®, a pretreatment blood-based test correlated with clinical outcome after EGFR-TKI therapy in non-small cell lung cancer (NSCLC) patients, was developed and validated in a multi-institutional study of advanced NSCLC patients treated with gefitinib [Taguchi et al] . The VeriStrat algorithm was developed using a training set of pre-treatment serum samples from patients who then experienced either long term stable disease or early progression on gefitinib therapy. Mass spectra from these patients' serum samples were used to define eight MS features (i.e. peaks), differentiating these two outcome groups. An algorithm (VeriStrat) utilizing these features and based on a k-nearest neighbors (KNN) classification scheme was created and its parameters were optimized using additional spectra from the training cohort. All aspects of VeriStrat were frozen after development. VeriStrat assigns each spectrum a "Good" or "Poor" label. VeriStrat was validated in a blinded fashion on two independent cohorts of patients who were treated with gefitinib or erlotinib. These studies confirmed that patients classified as "Good" had better outcome than patients classified as "Poor" (HR of death = 0.47 P = 0.0094 in one cohort, HR of death = 0.33 P = 0.0007 in the other).
In the original study, VeriStrat was shown to correlate with clinical outcome following EGFR-TKI therapy, but not in the chemotherapy or post-surgery setting: No statistically significant difference was seen in the overall survival of patients classified as "Good" or "Poor" from the serum from patients collected before second-line chemotherapy (HR = 0.74, 95%, P = 0.42 in one cohort (cohort B) and HR = 0.81, P = 0.54 in another (cohort C)). In a third control cohort of patients with resected early-stage NSCLC, the hazard ratio for overall survival was 0.90 (P = 0.79). However, further analysis of the subsets of chemotherapy samples demonstrated that separation between "Good" and "Poor" arms may depend on a particular type of chemotherapy. Thus a retrospective subset analysis of the cohort C showed that while patients treated with docetaxel in second line did not show any sign of separation, patients receiving a combination of platinum-based agents with either vinorelbine or gemcitabine or paclitaxel had a trend to separation between the two arms.
The working hypothesis for the mechanism is that the VeriStrat "Poor" label is related to the activation of canonical and non-canonical MAPK pathways downstream from receptor tyrosine kinases, with possible cross-talk activation of the NF-kB pathway. This means that VeriStrat may demonstrate different predictive performance depending on the particular chemotherapy treatment and its associated with cell pathway interactions.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non squamous histology | – | –patients with advanced, non-squamous non-small cell lung cancer treated with cisplatin (or carboplatin) and pemetrexed. Maintenance with pemetrexed is allowed. |
| Squamous histology | – | –patients with advanced squamous non-small cell lung cancer treated with cisplatin (or carboplatin) and gemcitabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients affected by advanced non small cell lung cancer who are chemotherapy-naive and candidates for first-line chemotherapy. This population includes patients with non-squamous histology and patients with squamous histology.
Key inclusion criteria (9 listed)
- Histologically or cytologically documented inoperable, locally advanced (stage IIIb with supraclavicular lymph node metastases),metastatic (stage IV) or recurrent NSCLC
- Age ≥18 years
- Life expectancy more than 3 months
- ECOG performance status 0-1
- At least one unidimensionally measurable lesion (as per RECIST criteria ver 1.1)
Key exclusion criteria (7 listed)
- Prior chemotherapy or treatment with another systemic anti-cancer agent (for example tyrosine kinase inhibitor).
- Patients must not receive any other investigational agents while on study
- Patients with myocardial infarction within the last six (6) months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
- History or evidence upon physical examination of CNS disease unless adequately treated (e.g., any brain metastasis, seizure not controlled with standard medical therapy, or history of stroke).
- Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol
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
Progression-free survival
Time frame: 2 years
The primary objective of this study is to evaluate the potential role of VeriStrat test as a biomarker of benefit from treatment with standard chemotherapy regimens in first line NSCLC patients in terms of progression-free survival (PFS) (primary endpoint) in two populations: patients with non-squamous histology treated with cisplatin and pemetrexed, and patients with squamous histology treated with cisplatin and gemcitabine
6 secondary outcomes
Overall survival
Time frame: 2 years
Correlation with RECIST response
Time frame: Every 6 weeks
Correlation with known biomarkers
Time frame: Every 6 weeks
Changes of VeriStrat with disease progression
Time frame: Every 6 weeks
Metabolomics
Time frame: Every 6 weeks
Circulating tumor cells.
Time frame: Every 6 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2017.
- Derived from this study: PubMed 28450567Morbelli S, Alama A, Ferrarazzo G, Coco S, Genova C, Rijavec E, Bongioanni F, Biello F, Dal Bello MG, Barletta G, Massollo M, Vanni I, Piva R, Nieri A, Bauckneht M, Sambuceti G, Grossi F. Circulating Tumor DNA Reflects Tumor Metabolism Rather Than Tumor Burden in Chemotherapy-Naive Patients with Advanced Non-Small Cell Lung Cancer: 18F-FDG PET/CT Study. J Nucl Med. 2017 Nov;58(11):1764-1769. doi: 10.2967/jnumed.117.193201. Epub 2017 Apr 27.
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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.
Francesco Grossi, MD contact
Francesco Grossi, MD principal investigator
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
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 Non Small Cell Lung Cancer, run by IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy at 1 site in Italy.
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 9 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 7 Mar 2017. 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 Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Francesco Grossi, MD (+39 010 5600 385), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02055144, which also lists 1 linked publication.
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 7 Mar 2017.