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

NCT ID: NCT01652469

Last Updated: 2022-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2015-12-31

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.

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

Conditions

Carcinoma, Non-Small-Cell Lung

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A: Erlotinib

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

Group Type: EXPERIMENTAL

Erlotinib

Intervention Type: DRUG

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

B: Docetaxel

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

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

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

Interventions

Erlotinib

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

Intervention Type: DRUG

Docetaxel

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

Intervention Type: DRUG

Other Intervention Names

Tarceva (Roche); Taxotere (Sanofi-Aventis)

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biodesix, Inc.

INDUSTRY

Sponsor Role: collaborator

ETOP IBCSG Partners Foundation

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Solange Peters, MD-PhD

Role: STUDY_CHAIR

Centre Pluridisciplinaire d'Oncologie, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland

Egbert Smit, MD-PhD

Role: STUDY_CHAIR

Vrije Universiteit VU, Medical Centre, 1007MB Amsterdam, The Netherlands

Rolf Stahel, MD

Role: STUDY_CHAIR

Laboratory of Molecular Oncology, Clinic of Oncology, University Hospital Zürich, 8044 Zürich, Switzerland

Locations

Krankenhaus Hietzing

Vienna, , Austria

Institut Jules Bordet

Brussels, , Belgium

Aarhus University Hospital

Aarhus, , Denmark

University Hospital of Heraklion

Heraklion, , Greece

National Institute of Oncology

Budapest, , Hungary

St James's Hospital

Dublin, , Ireland

Institution Rabin MC

Petah Tikwa, , Israel

Tel-Aviv Medical Center

Tel Aviv, , Israel

Medical Oncology, Second University Naples

Naples, , Italy

Vercelli Teaching Hospital

Vercelli, , Italy

Free University Medical Center

Amsterdam, , Netherlands

Hospital general de Alicante

Alicante, , Spain

Hospital Clínic Barcelona

Barcelona, , Spain

Institut Català d'Oncologia - L'Hospitalet

Barcelona, , Spain

Hospital San Pedro de Alcantara

Cáceres, , Spain

Ciudad Real General University Hospital

Ciudad Real, , Spain

Onkologikoa

Donostia / San Sebastian, , Spain

Hospital Severo Ochoa

Leganés, , Spain

Hospital 12 de Octubre

Madrid, , Spain

Carlos Haya Hospital

Málaga, , Spain

Hospital Universitari Sant Joan

Reus, , Spain

Hospital Arnau Vilanova Valencia

Valencia, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Hospital La Fe

Valencia, , Spain

University Hospital Basel

Basel, , Switzerland

Kantonsspital Graubünden

Chur, , Switzerland

Fondation du centre Pluridisciplinaire d'Oncologie (CePO)

Lausanne, , Switzerland

Kantonsspital Luzern

Lucerne, , Switzerland

Onkologiezentrum Berner Oberland

Thun, , Switzerland

Universitätsspital Zürich

Zurich, , Switzerland

University Hospital South Manchester

Manchester, , United Kingdom

Weston Park Hospital

Sheffield, , United Kingdom

Countries

Austria; Belgium; Denmark; Greece; Hungary; Ireland; Israel; Italy; Netherlands; Spain; Switzerland; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 19273711 (View on PubMed)

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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

PMID: 17909350 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15774793 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 1100130 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: Statistical Analysis Plan

View Document

Document Type: Statistical Analysis Plan: moc figures SAP

View Document

Document Type: Statistical Analysis Plan: moc tables SAP

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://www.etop-eu.org

Related information

Other Identifiers

2012-001896-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ETOP3-12

Identifier Type: -

Identifier Source: org_study_id