Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Veristrat as Predictor of Benefit of First Line Non Small Cell Lung Cancer (NSCLC) Patients From Standard Chemotherapy

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02055144
Recruitment Status : Unknown
Verified March 2017 by Francesco Grossi, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Recruitment status was:  Recruiting
First Posted : February 4, 2014
Last Update Posted : March 7, 2017
Sponsor:
Information provided by (Responsible Party):
Francesco Grossi, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

Tracking Information
First Submitted Date January 30, 2014
First Posted Date February 4, 2014
Last Update Posted Date March 7, 2017
Study Start Date February 2011
Estimated Primary Completion Date July 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: February 3, 2014)
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
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: February 3, 2014)
  • Overall survival [ Time Frame: 2 years ]
    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.
  • Correlation with RECIST response [ Time Frame: Every 6 weeks ]
    A secondary endpoint is to evaluate the possible correlation of VeriStrat classification with best RECIST responses.
  • Correlation with known biomarkers [ Time Frame: Every 6 weeks ]
    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.
  • Changes of VeriStrat with disease progression [ Time Frame: Every 6 weeks ]
    A secondary endpoint is to evaluate possible changes of VeriStrat classification with disease progression.
  • Metabolomics [ Time Frame: Every 6 weeks ]
    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.
  • Circulating tumor cells. [ Time Frame: Every 6 weeks ]
    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.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Veristrat as Predictor of Benefit of First Line Non Small Cell Lung Cancer (NSCLC) Patients From Standard Chemotherapy
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
Brief 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 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 Type Observational
Study Design Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Serum samples, urine samples, circulating tumour cells from peripheral blood. Such samples will be obtained before start of treatment (within 2 weeks), and at each patient's evaluation and at progression
Sampling Method Non-Probability Sample
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.
Condition Non Small Cell Lung Cancer
Intervention Not Provided
Study Groups/Cohorts
  • 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
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: (18)F-FDG PET/CT Study. J Nucl Med. 2017 Nov;58(11):1764-1769. doi: 10.2967/jnumed.117.193201. Epub 2017 Apr 27.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Unknown status
Estimated Enrollment
 (submitted: February 3, 2014)
100
Original Estimated Enrollment Same as current
Estimated Study Completion Date March 2018
Estimated Primary Completion Date July 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Italy
Removed Location Countries  
 
Administrative Information
NCT Number NCT02055144
Other Study ID Numbers VERISTRAT/IST
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Francesco Grossi, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Study Sponsor IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Collaborators Not Provided
Investigators
Principal Investigator: Francesco Grossi, MD IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
PRS Account IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Verification Date March 2017