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

NCT01652469 | Completed Phase 3 Results DMC

• 2 other identifiers: ETOP3-122012-001896-35
• Study Type: interventional
• Target: 81
• Locations: 12 countries
• Sites: 32

Brief Summary

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.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

squamous cell; NSCLC; TKI; Erlotinib; Docetaxel; VeriStrat; protein signature

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  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

  The combined run in period, treatment and follow-up for PFS is expected to extend the study duration to a total of 24 months.

Secondary Outcomes (4)

• Overall Survival

  All patients will be followed for survival status every 12 weeks up to 24 months after the last patient is randomized

• Objective Response

  Same as primary outcome: 24 months

• Disease Control

  Same as primary outcome: 24 months

• Number of Participants With Adverse Events

  Same as primary outcome: 24 months

Study Arms (2)

A: Erlotinib

EXPERIMENTAL

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

Drug: Erlotinib

B: Docetaxel

EXPERIMENTAL

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

Drug: Docetaxel

Interventions

Erlotinib DRUG

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

Also known as: Tarceva (Roche)

A: Erlotinib

Docetaxel DRUG

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

Also known as: Taxotere (Sanofi-Aventis)

B: Docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• Biodesix, Inc.: collaborator

Study Sites (32)

Krankenhaus Hietzing

Vienna, Austria

Location

Institut Jules Bordet

Brussels, Belgium

Location

Aarhus University Hospital

Aarhus, Denmark

Location

University Hospital of Heraklion

Heraklion, Greece

Location

National Institute of Oncology

Budapest, Hungary

Location

St James's Hospital

Dublin, Ireland

Location

Institution Rabin MC

Petah Tikwa, Israel

Location

Tel-Aviv Medical Center

Tel Aviv, Israel

Location

Medical Oncology, Second University Naples

Naples, Italy

Location

Vercelli Teaching Hospital

Vercelli, Italy

Location

Free University Medical Center

Amsterdam, 1007 MB, Netherlands

Location

Hospital general de Alicante

Alicante, Spain

Location

Hospital Clínic Barcelona

Barcelona, 08036, Spain

Location

Institut Català d'Oncologia - L'Hospitalet

Barcelona, Spain

Location

Hospital San Pedro de Alcantara

Cáceres, Spain

Location

Ciudad Real General University Hospital

Ciudad Real, Spain

Location

Onkologikoa

Donostia / San Sebastian, Spain

Location

Hospital Severo Ochoa

Leganés, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Carlos Haya Hospital

Málaga, Spain

Location

Hospital Universitari Sant Joan

Reus, Spain

Location

Hospital Arnau Vilanova Valencia

Valencia, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Spain

Location

Hospital La Fe

Valencia, Spain

Location

University Hospital Basel

Basel, 4031, Switzerland

Location

Kantonsspital Graubünden

Chur, Switzerland

Location

Fondation du centre Pluridisciplinaire d'Oncologie (CePO)

Lausanne, 1011, Switzerland

Location

Kantonsspital Luzern

Lucerne, 6016, Switzerland

Location

Onkologiezentrum Berner Oberland

Thun, 3600, Switzerland

Location

Universitätsspital Zürich

Zurich, Switzerland

Location

University Hospital South Manchester

Manchester, United Kingdom

Location

Weston Park Hospital

Sheffield, United Kingdom

Location

Related Publications (7)

• 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. doi: 10.1200/JCO.2008.17.5844. Epub 2009 Mar 9.

  PMID: 19273711 BACKGROUND

• 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. doi: 10.1200/JCO.2000.18.10.2095.

  PMID: 10811675 BACKGROUND

• 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. doi: 10.1056/NEJMoa050753.

  PMID: 16014882 BACKGROUND

• 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. doi: 10.1093/jnci/djk195.

  PMID: 17551144 BACKGROUND

• 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. doi: 10.1097/JTO.0b013e31814b8be7.

  PMID: 17909350 BACKGROUND

• 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. doi: 10.1200/JCO.2005.01.112.

  PMID: 15774793 BACKGROUND

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

  PMID: 1100130 BACKGROUND

Related Links

• Related information

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Heidi Roschitzki-Voser, Lead Trial Activities
• Organization: European Thoracic Oncology Platform (ETOP)

Heidi.Roschitzki@etop-eu.org

+41 31 511 94 18

Study Officials

• 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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2012
• First Posted: July 30, 2012
• Study Start: August 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: August 24, 2022
• Results First Posted: August 8, 2019

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1); IE (1); GR (1); GB (2); IL (2); NL (1); AU (1); IT (2); BE (1); DK (1); CH (6); ES (13)