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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Biodesix Inc.
Information provided by (Responsible Party):
European Thoracic Oncology Platform
ClinicalTrials.gov Identifier:
NCT01652469
First received: July 26, 2012
Last updated: January 17, 2014
Last verified: January 2014
  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:


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:

  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

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

  Show 32 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:
Publications:

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: January 17, 2014
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, Non-Small-Cell Lung
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Docetaxel
Erlotinib
Antimitotic Agents
Antineoplastic Agents
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 20, 2014