Clinical trial NCT01933932: Assess Efficacy & Safety of Selumetinib in Combination With Docetaxel in Patients Receiving 2nd Line Treatment for v-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Positive NSCLC
Official title: A Phase III, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy and Safety of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Combination With Docetaxel, in Patients Receiving Second Line Treatment for KRAS Mutation-Positive Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB - IV) (SELECT 1)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Locally Advanced or Metastatic Non Small Cell Lung Cancer Stage IIIb - IV
Keywords: Mitogen-Activated Protein Kinase Kinase inhibitor; Non Small Cell Lung Cancer; metastatic; second line treatment for Non Small Cell Lung Cancer; KRAS mutation
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2013-09-02
Enrollment: 510
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy of selumetinib in combination with docetaxel (75mg/m2) vs placebo in combination with docetaxel (75mg/m2) in patients with locally advance or metastatic NSCLCs that harbor mutations of KRAS. This study will also assess the PK, safety, patient reported outcomes (PRO) and tolerability profile of the selumetinib/docetaxel combination, compared to placebo in combination with docetaxel

Detailed description: A Phase III, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy and Safety of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Combination with Docetaxel, in Patients receiving second line treatment for KRAS Mutation-Positive Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB - IV) (SELECT-1)

Eligibility criteria: Inclusion Criteria:

* Provision of signed, written and dated informed consent prior to any study specific procedures
* Male or female, aged 18 years or older
* Histological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB-IV)
* KRAS mutation positive tumour sample as determined by the designated testing laboratory
* Failure of 1st line anti-cancer therapy due to radiological documentation of disease progression in advanced disease or subsequent relapse of disease following 1st line therapy

Exclusion Criteria:

* Mixed small cell and non-small cell lung cancer histology.
* Received \>1 prior anti-cancer drug regimen for advanced or metastatic NSCLC. Patients who develop disease progression while on switch maintenance therapy (maintenance using an agent not in the first-line regimen) will not be eligible.
* Receiving or have received systemic anti-cancer therapy within 30 days prior to starting study treatment
* Other concomitant anti-cancer therapy agents excepts steroids
* Prior treatment with a Mitogen-Activated protein Kinase (MEK) inhibitor or any docetaxel-containing regimen (prior treatment with paclitaxel is acceptable).
* Last radiation therapy within 4 weeks prior starting study treatment, or limited field of radiation for palliation within 7 days of the first dose of study treatment

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Measured at baseline until date of death due to any cause. Estimated final completion : approximately 3.5 years after FSI
measure: Objective Response Rate (ORR)
timeFrame: Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)
measure: Duration of Response (DoR)
timeFrame: Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)
measure: Symptom Improvement Rate Using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS)
timeFrame: Measured from date of randomisation until 30 days post treatment discontinuation or 30 days post progression (if study treatment is discontinued before progression). Estimated final completion : approximately 3 years after first subject in (FSI)
measure: Time to Symptom Progression Using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS)
timeFrame: Measured from date of randomisation until 30 days post treatment discontinuation or 30 days post progression (if study treatment is discontinued before progression). Estimated final completion : approximately 3 years after first subject in (FSI)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Pembroke Pines
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
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state: Illinois
city: Metairie
country: United States
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state: Louisiana
city: Boston
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state: Massachusetts
city: Boston
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state: Massachusetts
city: Danvers
country: United States
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state: Massachusetts
city: New York
country: United States
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state: New York
city: New York
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state: New York
city: Durham
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state: North Carolina
city: Hershey
country: United States
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state: Pennsylvania
city: Philadelphia
country: United States
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city: Nashville
country: United States
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city: Nashville
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state: Tennessee
city: Seattle
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state: Washington
city: Morgantown
country: United States
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state: West Virginia
city: Buenos Aires
country: Argentina
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city: Buenos Aires
country: Argentina
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city: Ciudad de Buenos Aires
country: Argentina
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country: Argentina
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country: Argentina
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country: Australia
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country: Australia
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city: Darlinghurst
country: Australia
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city: Fitzroy
country: Australia
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country: Australia
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city: Kurralta Park
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city: Malvern
country: Australia
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city: Wendouree
country: Australia
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city: Woodville South
country: Australia
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city: Innsbruck
country: Austria
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city: Linz
country: Austria
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city: Salzburg
country: Austria
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city: Vienna
country: Austria
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city: Wien
country: Austria
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city: Brussels
country: Belgium
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city: Bruxelles
country: Belgium
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city: Bruxelles
country: Belgium
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city: Gent
country: Belgium
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city: Leuven
country: Belgium
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city: Roeselare
country: Belgium
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city: Barretos
country: Brazil
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city: Ijui
country: Brazil
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city: Pelotas
country: Brazil
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city: Porto Alegre
country: Brazil
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country: Brazil
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country: Brazil
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country: Brazil
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city: São José do Rio Preto
country: Brazil
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country: Brazil
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city: Plovdiv
country: Bulgaria
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city: Sofia
country: Bulgaria
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country: Bulgaria
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country: Bulgaria
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country: Bulgaria
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country: Bulgaria
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city: Edmonton
country: Canada
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state: Alberta
city: Kelowna
country: Canada
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city: Surrey
country: Canada
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city: Toronto
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city: Montreal
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city: Regina
country: Canada
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city: Saskatoon
country: Canada
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state: Saskatchewan
city: Quebec
country: Canada
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city: Santiago
country: Chile
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city: Santiago
country: Chile
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city: Santiago
country: Chile
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city: Santiago
country: Chile
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city: Santiago
country: Chile
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city: Santiago
country: Chile
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city: Brest Cedex
country: France
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country: France
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country: France
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country: France
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country: France
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city: Marseille Cedex 20
country: France
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city: Paris
country: France
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city: Pierre Benite Cedex
country: France
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city: RENNES Cedex 9
country: France
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city: Toulouse Cedex 09
country: France
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city: Augsburg
country: Germany
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city: Bad Berka
country: Germany
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city: Dortmund
country: Germany
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city: Gerlingen
country: Germany
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city: Grosshansdorf
country: Germany
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city: Halle
country: Germany
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city: Heidelberg
country: Germany
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city: Homburg
country: Germany
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city: Köln
country: Germany
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city: Löwenstein
country: Germany
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country: Germany
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city: München
country: Germany
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city: Ulm
country: Germany
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city: Wiesbaden
country: Germany
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city: Würzburg
country: Germany
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city: Budapest
country: Hungary
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city: Budapest
country: Hungary
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city: Edelény
country: Hungary
facility: Research Site
city: Győr
country: Hungary
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city: Kaposvár
country: Hungary
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city: Miskolc
country: Hungary
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city: Nyíregyháza
country: Hungary
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country: Hungary
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city: Beer Sheva
country: Israel
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country: Israel
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country: Israel
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city: Petah Tikva
country: Israel
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city: Tel Hashomer
country: Israel
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city: Tel-Aviv
country: Israel
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city: Bari
country: Italy
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city: Genova
country: Italy
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city: Livorno
country: Italy
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city: Milano
country: Italy
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city: Napoli
country: Italy
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country: Italy
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country: Italy
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country: Italy
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country: Italy
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city: Mexico
country: Mexico
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city: Monterrey
country: Mexico
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city: Amsterdam
country: Netherlands
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city: Amsterdam
country: Netherlands
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country: Netherlands
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city: Den Bosch
country: Netherlands
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city: Maastricht
country: Netherlands
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city: Lima
country: Peru
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city: Lima
country: Peru
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city: Lima
country: Peru
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city: Lima
country: Peru
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city: Lima
country: Peru
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country: Peru
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country: Peru
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city: Brzozow
country: Poland
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city: Bydgoszcz
country: Poland
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country: Poland
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country: Poland
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country: Poland
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country: Poland
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country: Poland
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country: Poland
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country: Poland
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city: Sucha Beskidzka
country: Poland
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city: Szczecin
country: Poland
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city: Warszawa
country: Poland
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city: Amadora
country: Portugal
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city: Coimbra
country: Portugal
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city: Lisboa
country: Portugal
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city: Lisboa
country: Portugal
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city: Porto
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Vila Nova de Gaia
country: Portugal
facility: Research Site
city: Cluj Napoca
country: Romania
facility: Research Site
city: Cluj Napoca
country: Romania
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Volgograd
country: Russian Federation
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Vigo(Pontevedra)
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Linköping
country: Sweden
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
city: Örebro
country: Sweden
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: İstanbul
country: Turkey
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city: Izmir
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Manisa
country: Turkey
facility: Research Site
city: Chernivtsі
country: Ukraine
facility: Research Site
city: Dnipro
country: Ukraine
facility: Research Site
city: Kharkiv Region
country: Ukraine
facility: Research Site
city: Kryvyi Rih
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Sumy
country: Ukraine
facility: Research Site
city: Uzhhorod
country: Ukraine
facility: Research Site
city: Zaporizhzhia
country: Ukraine
facility: Research Site
city: Aberdeen
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
city: Wolverhampton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca UK, MSD
name: Gabriella Mariani, MD
role: STUDY_CHAIR
affiliation: Dana-Faber Cancer Institute, USA
name: Pasi Jänne, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Janne PA, van den Heuvel MM, Barlesi F, Cobo M, Mazieres J, Crino L, Orlov S, Blackhall F, Wolf J, Garrido P, Poltoratskiy A, Mariani G, Ghiorghiu D, Kilgour E, Smith P, Kohlmann A, Carlile DJ, Lawrence D, Bowen K, Vansteenkiste J. Selumetinib Plus Docetaxel Compared With Docetaxel Alone and Progression-Free Survival in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer: The SELECT-1 Randomized Clinical Trial. JAMA. 2017 May 9;317(18):1844-1853. doi: 10.1001/jama.2017.3438.
citation: Janne PA, Mann H, Ghiorghiu D. Study Design and Rationale for a Randomized, Placebo-Controlled, Double-Blind Study to Assess the Efficacy and Safety of Selumetinib in Combination With Docetaxel as Second-Line Treatment in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer (SELECT-1). Clin Lung Cancer. 2016 Mar;17(2):e1-4. doi: 10.1016/j.cllc.2015.12.010. Epub 2015 Dec 30.