Clinical trial NCT01652469: Testing of Drugs Erlotinib and Docetaxel in Lung Cancer Patients Classified Regarding Their Outlook Using VeriStrat®.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: squamous cell
NSCLC
TKI
Erlotinib
Docetaxel
VeriStrat
protein signature
Lead sponsor: ETOP IBCSG Partners Foundation
Sponsor class: NETWORK
Collaborators: name: Biodesix, Inc.
First posted: 2012-07-30
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Progression-free Survival
timeFrame: 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:
measure: Overall Survival
timeFrame: All patients will be followed for survival status every 12 weeks up to 24 months after the last patient is randomized
measure: Objective Response
timeFrame: Same as primary outcome: 24 months
measure: Disease Control
timeFrame: Same as primary outcome: 24 months
measure: Number of Participants With Adverse Events
timeFrame: Same as primary outcome: 24 months
Other outcomes:
Locations:
city: Wien
country: Austria
facility: Krankenhaus Hietzing
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Heraklion
country: Greece
facility: University Hospital of Heraklion
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Dublin
country: Ireland
facility: St James's Hospital
city: Petah Tikwa
country: Israel
facility: Institution Rabin MC
city: Tel-Aviv
country: Israel
facility: Tel-Aviv Medical Center
city: Naples
country: Italy
facility: Medical Oncology, Second University Naples
city: Vercelli
country: Italy
facility: Vercelli Teaching Hospital
city: Amsterdam
country: Netherlands
facility: Free University Medical Center
city: Alicante
country: Spain
facility: Hospital general de Alicante
city: Barcelona
country: Spain
facility: Hospital Clínic Barcelona
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia - L'Hospitalet
city: Ciudad Real
country: Spain
facility: Ciudad Real General University Hospital
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Donostia
country: Spain
facility: Onkologikoa
city: Leganés
country: Spain
facility: Hospital Severo Ochoa
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Malaga
country: Spain
facility: Carlos Haya Hospital
city: Reus
country: Spain
facility: Hospital Universitari Sant Joan
city: Valencia
country: Spain
facility: Hospital Arnau Vilanova Valencia
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital La Fe
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden
city: Lausanne
country: Switzerland
facility: Fondation du centre Pluridisciplinaire d'Oncologie (CePO)
city: Luzern
country: Switzerland
facility: Kantonsspital Luzern
city: Thun
country: Switzerland
facility: Onkologiezentrum Berner Oberland
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
city: Manchester
country: United Kingdom
facility: University Hospital South Manchester
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
Study officials:
affiliation: Centre Pluridisciplinaire d'Oncologie, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
name: Solange Peters, MD-PhD
role: STUDY_CHAIR
affiliation: Vrije Universiteit VU, Medical Centre, 1007MB Amsterdam, The Netherlands
name: Egbert Smit, MD-PhD
role: STUDY_CHAIR
affiliation: Laboratory of Molecular Oncology, Clinic of Oncology, University Hospital Zürich, 8044 Zürich, Switzerland
name: Rolf Stahel, MD
role: STUDY_CHAIR
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