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

NCT ID: NCT01933932

Last Updated: 2025-11-19

Study Results

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

510 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-25

Study Completion Date

2025-12-31

Brief Summary

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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

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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)

Conditions

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Locally Advanced or Metastatic Non Small Cell Lung Cancer Stage IIIb - IV

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Selumetinib + Docetaxel

Three 25mg Selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle

Group Type EXPERIMENTAL

Selumetinib

Intervention Type DRUG

Three 25 mg selumetinib capsules (Hyd-Sulfate) be administered orally, twice daily, (total dose 75 mg dose bd) on an uninterrupted schedule.

Docetaxel

Intervention Type DRUG

Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.

Pegylated G-CSF

Intervention Type DRUG

All patients will receive pegylated Granulocyte Colony Stimulating Factor (G-CSF) at least 24 hours after administration of every docetaxel dose and not within 14 days prior to the next docetaxel administration.

Placebo + Docetaxel

Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.

Group Type EXPERIMENTAL

Docetaxel

Intervention Type DRUG

Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.

Placebo

Intervention Type DRUG

Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.

Pegylated G-CSF

Intervention Type DRUG

All patients will receive pegylated Granulocyte Colony Stimulating Factor (G-CSF) at least 24 hours after administration of every docetaxel dose and not within 14 days prior to the next docetaxel administration.

Interventions

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Selumetinib

Three 25 mg selumetinib capsules (Hyd-Sulfate) be administered orally, twice daily, (total dose 75 mg dose bd) on an uninterrupted schedule.

Intervention Type DRUG

Docetaxel

Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.

Intervention Type DRUG

Placebo

Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.

Intervention Type DRUG

Pegylated G-CSF

All patients will receive pegylated Granulocyte Colony Stimulating Factor (G-CSF) at least 24 hours after administration of every docetaxel dose and not within 14 days prior to the next docetaxel administration.

Intervention Type DRUG

Other Intervention Names

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AZD6244; ARRY-142886 Pegfilgrastim 6 mg

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gabriella Mariani, MD

Role: STUDY_CHAIR

AstraZeneca UK, MSD

Pasi Jänne, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Faber Cancer Institute, USA

Locations

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Aurora, Colorado, United States

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Pembroke Pines, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Metairie, Louisiana, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Danvers, Massachusetts, United States

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New York, New York, United States

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New York, New York, United States

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Durham, North Carolina, United States

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Hershey, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Nashville, Tennessee, United States

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Nashville, Tennessee, United States

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Seattle, Washington, United States

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Morgantown, West Virginia, United States

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Buenos Aires, , Argentina

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Ciudad de Buenos Aires, , Argentina

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Ciudad de Buenos Aires, , Argentina

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Córdoba, , Argentina

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Rosario, , Argentina

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Camperdown, , Australia

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Chermside, , Australia

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Darlinghurst, , Australia

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Fitzroy, , Australia

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Kogarah, , Australia

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Kurralta Park, , Australia

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Malvern, , Australia

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Wendouree, , Australia

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Woodville South, , Australia

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Innsbruck, , Austria

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Linz, , Austria

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Salzburg, , Austria

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Vienna, , Austria

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Vienna, , Austria

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Brussels, , Belgium

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Brussels, , Belgium

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Brussels, , Belgium

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Ghent, , Belgium

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Leuven, , Belgium

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Roeselare, , Belgium

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Barretos, , Brazil

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Ijuí, , Brazil

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Pelotas, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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São José do Rio Preto, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Vratsa, , Bulgaria

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Edmonton, Alberta, Canada

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Kelowna, British Columbia, Canada

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Surrey, British Columbia, Canada

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Halifax, Nova Scotia, Canada

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Oshawa, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Regina, Saskatchewan, Canada

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Saskatoon, Saskatchewan, Canada

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Santiago, , Chile

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Santiago, , Chile

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Santiago, , Chile

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Santiago, , Chile

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Santiago, , Chile

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Brest, , France

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Caen, , France

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Clermont-Ferrand, , France

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Dijon, , France

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Lille, , France

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Marseille, , France

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Paris, , France

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Pierre-Bénite, , France

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Rennes, , France

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Toulouse, , France

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Augsburg, , Germany

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Bad Berka, , Germany

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Cologne, , Germany

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Dortmund, , Germany

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Gerlingen, , Germany

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Großhansdorf, , Germany

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Halle, , Germany

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Heidelberg, , Germany

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Homburg, , Germany

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Löwenstein, , Germany

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Moers, , Germany

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München, , Germany

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Ulm, , Germany

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Wiesbaden, , Germany

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Würzburg, , Germany

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Budapest, , Hungary

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Budapest, , Hungary

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Edelény, , Hungary

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Győr, , Hungary

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Kaposvár, , Hungary

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Miskolc, , Hungary

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Nyíregyháza, , Hungary

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Törökbálint, , Hungary

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Beersheba, , Israel

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Haifa, , Israel

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Kfar Saba, , Israel

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Petah Tikva, , Israel

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Tel Aviv, , Israel

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Tel Litwinsky, , Israel

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Bari, , Italy

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Genova, , Italy

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Livorno, , Italy

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Milan, , Italy

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Napoli, , Italy

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Orbassano, , Italy

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Parma, , Italy

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Perugia, , Italy

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Roma, , Italy

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Roma, , Italy

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México, , Mexico

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Monterrey, , Mexico

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's-Hertogenbosch, , Netherlands

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Amsterdam, , Netherlands

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Amsterdam, , Netherlands

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Bergen op Zoom, , Netherlands

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Maastricht, , Netherlands

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Lima, , Peru

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Miraflores, , Peru

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Brzozów, , Poland

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Bydgoszcz, , Poland

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Gdansk, , Poland

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Gdansk, , Poland

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Grudziądz, , Poland

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Krakow, , Poland

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Lubin, , Poland

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Olsztyn, , Poland

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Opole, , Poland

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Sucha Beskidzka, , Poland

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Szczecin, , Poland

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Warsaw, , Poland

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Amadora, , Portugal

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Coimbra, , Portugal

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Lisbon, , Portugal

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Porto, , Portugal

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Porto, , Portugal

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Vila Nova de Gaia, , Portugal

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Cluj-Napoca, , Romania

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Cluj-Napoca, , Romania

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Kazan', , Russia

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Moscow, , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Volgograd, , Russia

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Barcelona, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Seville, , Spain

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Vigo(Pontevedra), , Spain

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Zaragoza, , Spain

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Linköping, , Sweden

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Örebro, , Sweden

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Uppsala, , Sweden

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Manisa, , Turkey (Türkiye)

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Chernivtsі, , Ukraine

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Dnipro, , Ukraine

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Kharkiv Region, , Ukraine

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Kryvyi Rih, , Ukraine

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Kyiv, , Ukraine

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Sumy, , Ukraine

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Uzhhorod, , Ukraine

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Zaporizhzhia, , Ukraine

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Aberdeen, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Nottingham, , United Kingdom

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Sutton, , United Kingdom

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Wolverhampton, , United Kingdom

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Countries

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United States Argentina Australia Austria Belgium Brazil Bulgaria Canada Chile France Germany Hungary Israel Italy Mexico Netherlands Peru Poland Portugal Romania Russia Spain Sweden Turkey (Türkiye) Ukraine United Kingdom

References

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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.

Reference Type DERIVED
PMID: 28492898 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26837474 (View on PubMed)

Related Links

Other Identifiers

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2013-001676-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D1532C00079

Identifier Type: -

Identifier Source: org_study_id

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