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

Carcinoma, Non-Small-Cell Lung Clinical Trial

— EMPHASIS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01652469
• Other study ID #: ETOP3-12
• Secondary ID: 2012-001896-35
• Status: Completed
• Phase: Phase 3
• Start date: August 2012
• Est. completion date: December 2015

Study information

• Verified date: August 2022
• Source: ETOP IBCSG Partners Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Erlotinib
Erlotinib 150 mg/day p.o. continuously with 21 days cycle.
• Docetaxel
Docetaxel 75 mg/m2 as an IV infusion every 21 days.

Locations

Country	Name	City	State
Austria	Krankenhaus Hietzing	Wien
Belgium	Institut Jules Bordet	Brussels
Denmark	Aarhus University Hospital	Aarhus
Greece	University Hospital of Heraklion	Heraklion
Hungary	National Institute of Oncology	Budapest
Ireland	St James's Hospital	Dublin
Israel	Institution Rabin MC	Petah Tikwa
Israel	Tel-Aviv Medical Center	Tel-Aviv
Italy	Medical Oncology, Second University Naples	Naples
Italy	Vercelli Teaching Hospital	Vercelli
Netherlands	Free University Medical Center	Amsterdam
Spain	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
Spain	Hospital Severo Ochoa	Leganés
Spain	Hospital 12 de Octubre	Madrid
Spain	Carlos Haya Hospital	Malaga
Spain	Hospital Universitari Sant Joan	Reus
Spain	Hospital Arnau Vilanova Valencia	Valencia
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital La Fe	Valencia
Switzerland	University Hospital Basel	Basel
Switzerland	Kantonsspital Graubünden	Chur
Switzerland	Fondation du centre Pluridisciplinaire d'Oncologie (CePO)	Lausanne
Switzerland	Kantonsspital Luzern	Luzern
Switzerland	Onkologiezentrum Berner Oberland	Thun
Switzerland	Universitätsspital Zürich	Zürich
United Kingdom	University Hospital South Manchester	Manchester
United Kingdom	Weston Park Hospital	Sheffield

Sponsors (2)

Lead Sponsor	Collaborator
ETOP IBCSG Partners Foundation	Biodesix, Inc.

Countries where clinical trial is conducted

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

References & 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. — View Citation

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

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. — View Citation

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. — View Citation

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, Santabárbara 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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival	Defined as time from the date of randomization until death from any cause.	All patients will be followed for survival status every 12 weeks up to 24 months after the last patient is randomized
Secondary	Objective Response	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.	Same as primary outcome: 24 months
Secondary	Disease Control	Disease control is defined as achieving objective response or stable disease for at least 6 weeks.	Same as primary outcome: 24 months
Secondary	Number of Participants With Adverse Events	Adverse events classified according to NCI CTCAE version 4	Same as primary outcome: 24 months

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