Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Carcinoma

Lung Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Docetaxel

Erlotinib Hydrochloride

Tubulin Modulators

Antimitotic Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Erlotinib in standard dose. Until progression (clinical or radiological) or unacceptable toxicity.

Docetaxel in standard dose. Until progression (clinical or radiological) or unacceptable toxicity.

Erlotinib 150 mg/day p.o. continuously with 21 days cycle.

Erlotinib

Docetaxel 75 mg/m2 as an IV infusion every 21 days.

Solange Peters, MD-PhD

Egbert Smit, MD-PhD

Rolf Stahel, MD

Using a laboratory test (VeriStrat), patients with relapsed squamous cell lung cancer are assigned to two strata, VSG (VeriStrat Good) and VSP (VeriStrat Poor). They are then randomized between an EGFR-TK inhibitor (erlotinib) and chemotherapy (Docetaxel).

It is hypothesized that the VeriStrat test results are able to predict the benefit of treatment with erlotinib vs docetaxel. This would suggest a significant improvement in progression-free survival for VSG patients when treated with Erlotinib, and no significant improvement in VSP patients who receive the same treatment.

Goals of the study:

1. Explore the predictive ability of the VeriStrat signature, by testing for interaction between treatment arms (Arm A: erlotinib vs Arm B: docetaxel) and VeriStrat status (VSG vs VSP) using as outcome progression free survival.
2. Explore whether treatment with erlotinib provides progression free survival benefit as compared to docetaxel in the VSG group.
3. Compare progression free survival in the two treatment arms (Arm A: erlotinib vs Arm B: docetaxel) in the VSP group.
4. Explore the prognostic ability of the VeriStrat signature by testing for an overall difference in progression free survival between the two VeriStrat groups (in case of no significant interaction).
5. Explore the predictive ability of the VeriStrat signature using the secondary measures of clinical efficacy including overall survival, objective response rate, and disease control rate.
6. Compare overall survival, objective response rate and disease control rate between treatment groups separately in the VSG and VSP groups.
7. Explore the prognostic ability of the VeriStrat signature by testing for an overall difference in overall survival, objective response rate and disease control rate between the two VeriStrat groups (in case of no significant interaction).
8. Assess the safety and the tolerability of the two treatments separately in each VeriStrat group and overall.

Recruitment period: 18 months Sample Size: 500

Testing of Drugs Erlotinib and Docetaxel in Lung Cancer Patients Classified Regarding Their Outlook Using VeriStrat®.

A Randomized Phase III Trial of Erlotinib Versus Docetaxel in Patients With Advanced Squamous Cell Non-small Cell Lung Cancer Who Failed First Line Platinum Based Doublet Chemotherapy Stratified by VeriStrat Good vs VeriStrat Poor

Time from the date of randomization until documented progression or death without documented progression.

Assessment of Progressive Disease (PD) based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) Target lesions:At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.(Note: the appearance of one or more new lesions is also considered progression).

Non-target lesions:Unequivocal progression of existing non-target lesions. (Note:the appearance of one or more new lesions is also considered progression). To achieve 'unequivocal progression', there must be an overall level of substantial worsening in non-target disease such that,even in presence of SD or PR in target disease, the overall tumour burden has increased sufficiently

Defined as time from the date of randomization until death from any cause.

Objective response is defined as best overall response (CR or PR) across all assessment time-points according to RECIST Criteria 1.1 during the period from randomization to termination of trial treatment.

Disease control is defined as achieving objective response or stable disease for at least 6 weeks.

Adverse events classified according to NCI CTCAE version 4

Biodesix, Inc.

ETOP IBCSG Partners Foundation

One patient from the Docetaxel arm never started treatment.

Erlotinib in standard dose. Until progression (clinical or radiological) or unacceptable toxicity.

Erlotinib: Erlotinib 150 mg/day p.o. continuously with 21 days cycle.

A: Erlotinib

Docetaxel in standard dose. Until progression (clinical or radiological) or unacceptable toxicity.

Docetaxel: Docetaxel 75 mg/m2 as an IV infusion every 21 days.

B: Docetaxel

Total

Age, Continuous

Sex: Female, Male

Smoking history

ECOG Performance status scaling:

PS 0:Fully active, able to carry on all pre-disease performance without restriction PS 1:Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work PS 2:Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours PS 3:Capable of only limited self-care, confined to bed or chair more than 50% of waking hours PS 4:Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair

ECOG performance status

VeriStrat status

Heidi Roschitzki-Voser, Lead Trial Activities

Progression-free Survival

Overall Survival

Objective Response

Disease Control

Experienced AE/SAE

No AE/SAE

Experienced SAE

Number of Participants With Adverse Events

Overall Study

Symptoms and General Pathology

Neoplastic Cells, Circulating

Gemcitabine

Carboplatin

Pemetrexed

Cisplatin

patients with advanced, non-squamous non-small cell lung cancer treated with cisplatin (or carboplatin) and pemetrexed. Maintenance with pemetrexed is allowed.

patients with advanced squamous non-small cell lung cancer treated with cisplatin (or carboplatin) and gemcitabine

Francesco Grossi, MD

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.

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.

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

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

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

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

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.

A secondary endpoint is to evaluate the possible correlation of VeriStrat classification with best RECIST responses.

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.

A secondary endpoint is to evaluate possible changes of VeriStrat classification with disease progression.

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Testing of Drugs Erlotinib and Docetaxel in Lung Cancer Patients Classified Regarding Their Outlook Using VeriStrat®.	NCT01652469	Carcinoma, Non-...	Erlotinib Docetaxel	18 Years -	ETOP IBCSG Partners Foundation
Veristrat as Predictor of Benefit of First Line Non Small Cell Lung Cancer (NSCLC) Patients From Standard Chemotherapy	NCT02055144	Non Small Cell ...		18 Years -	IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Testing of Drugs Erlotinib and Docetaxel in Lung Cancer Patients Classified Regarding Their Outlook Using VeriStrat®.	NCT01652469	Carcinoma, Non-...	Erlotinib Docetaxel	18 Years -	ETOP IBCSG Partners Foundation
Veristrat as Predictor of Benefit of First Line Non Small Cell Lung Cancer (NSCLC) Patients From Standard Chemotherapy	NCT02055144	Non Small Cell ...		18 Years -	IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Testing of Drugs Erlotinib and Docetaxel in Lung Cancer Patients Classified Regarding Their Outlook Using VeriStrat®.	NCT01652469	Carcinoma, Non-...	Erlotinib Docetaxel	18 Years -	ETOP IBCSG Partners Foundation

Spots Global Cancer Trial Database for veristrat

Every month we try and update this database with for veristrat cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for veristrat

Every month we try and update this database with for veristrat cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for veristrat cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.