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

Purpose

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.

Condition	Intervention	Phase
Carcinoma, Non-Small-Cell Lung	Drug: Erlotinib Drug: Docetaxel	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Docetaxel Erlotinib hydrochloride Erlotinib

U.S. FDA Resources

Further study details as provided by European Thoracic Oncology Platform:

Primary Outcome Measures:

Progression-free survival [ Time Frame: The combined run in period, treatment and follow-up for PFS is expected to extend the study duration to a total of 24 months. ] [ Designated as safety issue: No ]
Time from the date of randomization until documented progression or death without documented progression.

Secondary Outcome Measures:

Overall survival [ Time Frame: All patients will be followed for survival status every 12 weeks up to 24 months after the last patient is randomized ] [ Designated as safety issue: No ]
Defined as time from the date of randomization until death from any cause.
Objective response [ Time Frame: Same as primary outcome: 24 months ] [ Designated as safety issue: No ]
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 [ Time Frame: Same as primary outcome: 24 months ] [ Designated as safety issue: No ]
Disease control is defined as achieving objective response or stable disease for at least 6 weeks.
Toxicities of treatment [ Time Frame: Same as primary outcome: 24 months ] [ Designated as safety issue: Yes ]
Adverse events classified according to NCI CTCAE version 4

Estimated Enrollment:	500
Study Start Date:	August 2012
Estimated Study Completion Date:	August 2016
Estimated Primary Completion Date:	August 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A: Erlotinib Erlotinib in standard dose. Until progression (clinical or radiological) or unacceptable toxicity.	Drug: Erlotinib Erlotinib 150 mg/day p.o. continuously with 21 days cycle. Other Name: Tarceva (Roche)
Experimental: B: Docetaxel Docetaxel in standard dose. Until progression (clinical or radiological) or unacceptable toxicity.	Drug: Docetaxel Docetaxel 75 mg/m2 as an IV infusion every 21 days. Other Name: Taxotere (Sanofi-Aventis)

Detailed Description:

Goals of the study:

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.
Explore whether treatment with erlotinib provides progression free survival benefit as compared to docetaxel in the VSG group.
Compare progression free survival in the two treatment arms (Arm A: erlotinib vs Arm B: docetaxel) in the VSP group.
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).
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.
Compare overall survival, objective response rate and disease control rate between treatment groups separately in the VSG and VSP groups.
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).
Assess the safety and the tolerability of the two treatments separately in each VeriStrat group and overall.

Recruitment period: 18 months Sample Size: 500

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically or cytologically confirmed locally advanced stage IIIB, not amenable to radical radiotherapy, or metastatic stage IV non-small cell lung cancer (NSCLC) of predominant squamous subtype, according to the 7th edition of the TNM classification, including M1a (separate tumor nodule in a contralateral lobe, tumor with pleural nodules or malignant pleural or pericardial effusion) and/or M1b (distant metastasis).
Progressive disease upon or after previous chemotherapy including at least one line of platinum-based chemotherapy.
Measurable or evaluable disease according to RECIST v1.1 (Appendix 2).
ECOG PS 0-2.
Age ≥ 18 years.
Adequate organ function, including:
Adequate bone marrow reserve: ANC > 1.5 x 109/L, platelets > 100 x 109/L.
Hepatic: bilirubin <1.5 x ULN; AP, ALT < 3.0 x ULN; AP, ALT <5 x ULN is acceptable in case of liver metastasis.
Renal: calculated creatinine clearance > 40 ml/min based on the Cockroft and Gault formula.
Signed and dated informed consent form.
Male and female patients with reproductive potential must use an approved contraceptive method, during the trial and 12 months thereafter. Female patients with reproductive potential must have a negative pregnancy test within 7 days prior to study registration.
Estimated life expectancy >12 weeks.
Patient compliance and geographical proximity that allow adequate follow-up.

Exclusion Criteria:

Evidence of other medical condition which would impair the ability of the patient to participate in the trial or might preclude therapy with trial drugs (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease, active infection, uncontrolled diabetes mellitus).
Previous treatment with any EGFR-TKI or docetaxel.
Documented brain metastases unless the patient has completed local therapy for central nervous system metastases and has been off corticosteroids for at least 14 days prior to study registration.
Documented presence of activating EGFR mutations, if the patient was tested for EGFR mutations.
Previous malignancy within the past 5 years with the exception of adequately treated cervical carcinoma in situ, breast cancer in situ or localized non-melanoma skin cancer.
Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, or interfering with compliance for oral drug intake.
Concurrent treatment with experimental drugs or other anti-cancer therapy treatment in a clinical trial within 21 days prior to study registration.
Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs or any concomitant drugs contraindicated.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01652469

Contacts

Contact: Barbara Ruepp, PhD

+41313899391

emphasis@etop-eu.org

Show 47 Study Locations

Sponsors and Collaborators

European Thoracic Oncology Platform

Biodesix Inc.

Investigators

Study Chair:	Solange Peters, MD-PhD	Centre Pluridisciplinaire d'Oncologie, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
Study Chair:	Egbert Smit, MD-PhD	Vrije Universiteit VU, Medical Centre, 1007MB Amsterdam, The Netherlands
Study Chair:	Rolf Stahel, MD	Laboratory of Molecular Oncology, Clinic of Oncology, University Hospital Zürich, 8044 Zürich, Switzerland

More Information

Additional Information:

Related information This link exits the ClinicalTrials.gov site

Publications:

Di Maio M, Chiodini P, Georgoulias V, Hatzidaki D, Takeda K, Wachters FM, Gebbia V, Smit EF, Morabito A, Gallo C, Perrone F, Gridelli C. Meta-analysis of single-agent chemotherapy compared with combination chemotherapy as second-line treatment of advanced non-small-cell lung cancer. J Clin Oncol. 2009 Apr 10;27(11):1836-43. Epub 2009 Mar 9.

Shepherd FA, Dancey J, Ramlau R, Mattson K, Gralla R, O'Rourke M, Levitan N, Gressot L, Vincent M, Burkes R, Coughlin S, Kim Y, Berille J. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol. 2000 May;18(10):2095-103.

Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabarbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32.

Taguchi F, Solomon B, Gregorc V, Roder H, Gray R, Kasahara K, Nishio M, Brahmer J, Spreafico A, Ludovini V, Massion PP, Dziadziuszko R, Schiller J, Grigorieva J, Tsypin M, Hunsucker SW, Caprioli R, Duncan MW, Hirsch FR, Bunn PA Jr, Carbone DP. Mass spectrometry to classify non-small-cell lung cancer patients for clinical outcome after treatment with epidermal growth factor receptor tyrosine kinase inhibitors: a multicohort cross-institutional study. J Natl Cancer Inst. 2007 Jun 6;99(11):838-46.

Yildiz PB, Shyr Y, Rahman JS, Wardwell NR, Zimmerman LJ, Shakhtour B, Gray WH, Chen S, Li M, Roder H, Liebler DC, Bigbee WL, Siegfried JM, Weissfeld JL, Gonzalez AL, Ninan M, Johnson DH, Carbone DP, Caprioli RM, Massion PP. Diagnostic accuracy of MALDI mass spectrometric analysis of unfractionated serum in lung cancer. J Thorac Oncol. 2007 Oct;2(10):893-901.

Sargent DJ, Conley BA, Allegra C, Collette L. Clinical trial designs for predictive marker validation in cancer treatment trials. J Clin Oncol. 2005 Mar 20;23(9):2020-7. Review.

Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975 Mar;31(1):103-15.

Responsible Party:	European Thoracic Oncology Platform
ClinicalTrials.gov Identifier:	NCT01652469 History of Changes
Other Study ID Numbers:	ETOP3-12, 2012-001896-35
Study First Received:	July 26, 2012
Last Updated:	April 3, 2013
Health Authority:	Switzerland: Swissmedic United Kingdom: Medicines and Healthcare Products Regulatory Agency Spain: Agencia Española de Medicamentos y Productos Sanitarios France: Agence Nationale de Sécurité du Médicament et des produits de santé Germany: Federal Institute for Drugs and Medical Devices Italy: The Italian Medicines Agency Portugal: National Pharmacy and Medicines Institute Netherlands: Medicines Evaluation Board (MEB) Hungary: National Institute of Pharmacy Greece: National Organization of Medicines Denmark: Danish Medicines Agency Czech Republic: State Institute for Drug Control Belgium: Federal Agency for Medicinal Products and Health Products Austria: Agency for Health and Food Safety Israel: Israeli Health Ministry Pharmaceutical Administration Ireland: Irish Medicines Board

Keywords provided by European Thoracic Oncology Platform:

squamous cell
NSCLC
TKI
Erlotinib

Docetaxel
VeriStrat
protein signature

Additional relevant MeSH terms:

Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site

Lung Diseases
Respiratory Tract Diseases
Docetaxel
Erlotinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 17, 2013

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