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 (SELECT-1)

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)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Locally Advanced or Metastatic Non Small Cell Lung Cancer Stage IIIb - IV
• Intervention / Treatment: Drug: Selumetinib; Drug: Docetaxel; Drug: Pegylated G-CSF; Drug: Placebo

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)

• Study Type: Interventional
• Enrollment (Actual): 510
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1025ABI
    • Research Site
  • Buenos Aires, Argentina, 1426
    • Research Site
  • Ciudad de Buenos Aires, Argentina, 1180
    • Research Site
  • Cordoba, Argentina, 5000
    • Research Site
  • Rosario, Argentina, S2000KZE
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• Australia
  • Camperdown, Australia, 2050
    • Research Site
  • Chermside, Australia, 4032
    • Research Site
  • Darlinghurst, Australia, 2010
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  • Fitzroy, Australia, 3065
    • Research Site
  • Kogarah, Australia, 2217
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  • Kurralta Park, Australia, 5037
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  • Malvern, Australia, 3144
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  • Wendouree, Australia, 3355
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  • Woodville South, Australia, 5011
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• Austria
  • Innsbruck, Austria, 6020
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  • Linz, Austria, 4020
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  • Salzburg, Austria, 5020
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  • Vienna, Austria, 1160
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  • Wien, Austria, 1100
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• Belgium
  • Brussels, Belgium, 1090
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  • Bruxelles, Belgium, 1200
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  • Bruxelles, Belgium, 1000
    • Research Site
  • Gent, Belgium, 9000
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Roeselare, Belgium, 8800
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• Brazil
  • Barretos, Brazil, 14784-400
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  • Ijui, Brazil, 98700-000
    • Research Site
  • Pelotas, Brazil, 096015-280
    • Research Site
  • Porto Alegre, Brazil, 90035-003
    • Research Site
  • Porto Alegre, Brazil, 90610-000
    • Research Site
  • Sao Paulo, Brazil
    • Research Site
  • Sao Paulo, Brazil, 01246-000
    • Research Site
  • Sao Paulo, Brazil, 01209-000
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Research Site
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • Research Site
  • Sofia, Bulgaria, 1233
    • Research Site
  • Sofia, Bulgaria, 1330
    • Research Site
  • Sofia, Bulgaria, 1303
    • Research Site
  • Varna, Bulgaria, 9010
    • Research Site
  • Vratza, Bulgaria, 3000
    • Research Site
• Canada
  • Quebec, Canada, G1V 4G5
    • Research Site
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Research Site
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • Research Site
    • Surrey, British Columbia, Canada, V3V 1Z2
      • Research Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Research Site
  • Ontario
    • Oshawa, Ontario, Canada, L1G 2B9
      • Research Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Research Site
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Research Site
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Research Site
• Chile
  • Santiago, Chile, 7520349
    • Research Site
  • Santiago, Chile, 8360160
    • Research Site
  • Santiago, Chile, 7500921
    • Research Site
  • Santiago, Chile, 8380456
    • Research Site
  • Santiago, Chile, 8420383
    • Research Site
  • Santiago, Chile, 7630370
    • Research Site
• France
  • Brest Cedex, France, 29609
    • Research Site
  • Caen, France, F-14033
    • Research Site
  • Clermont Ferrand, France, 63003
    • Research Site
  • Dijon, France, 21079
    • Research Site
  • Lille, France, 59000
    • Research Site
  • Marseille Cedex 20, France, 13915
    • Research Site
  • Paris, France, 75020
    • Research Site
  • Pierre Benite Cedex, France, 69310
    • Research Site
  • RENNES Cedex 9, France, 35033
    • Research Site
  • Toulouse Cedex 09, France, 31059
    • Research Site
• Germany
  • Augsburg, Germany, 86156
    • Research Site
  • Bad Berka, Germany, 99437
    • Research Site
  • Dortmund, Germany, 44309
    • Research Site
  • Gerlingen, Germany, 70839
    • Research Site
  • Großhansdorf, Germany, 22927
    • Research Site
  • Halle, Germany, 06120
    • Research Site
  • Heidelberg, Germany, 69126
    • Research Site
  • Homburg, Germany, 66424
    • Research Site
  • Köln, Germany, 50937
    • Research Site
  • Löwenstein, Germany, 74245
    • Research Site
  • Moers, Germany, 47441
    • Research Site
  • München, Germany, 81925
    • Research Site
  • Ulm, Germany, 89081
    • Research Site
  • Wiesbaden, Germany, 65199
    • Research Site
  • Würzburg, Germany, 97080
    • Research Site
• Hungary
  • Budapest, Hungary, 1121
    • Research Site
  • Budapest, Hungary, 1122
    • Research Site
  • Edelény, Hungary, 3780
    • Research Site
  • Győr, Hungary, 9024
    • Research Site
  • Kaposvár, Hungary, 7400
    • Research Site
  • Miskolc, Hungary, 3529
    • Research Site
  • Nyíregyháza, Hungary, 4400
    • Research Site
  • Törökbálint, Hungary, 2045
    • Research Site
• Israel
  • Beer Sheva, Israel, 8410101
    • Research Site
  • Haifa, Israel, 31096
    • Research Site
  • Kfar Saba, Israel, 4428164
    • Research Site
  • Petah Tikva, Israel, 49100
    • Research Site
  • Tel Hashomer, Israel, 52621
    • Research Site
  • Tel-Aviv, Israel, 64239
    • Research Site
• Italy
  • Bari, Italy, 70124
    • Research Site
  • Genova, Italy, 16100
    • Research Site
  • Livorno, Italy, 57100
    • Research Site
  • Milano, Italy, 20132
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
  • Orbassano, Italy, 10043
    • Research Site
  • Parma, Italy, 43126
    • Research Site
  • Perugia, Italy, 06132
    • Research Site
  • Roma, Italy, 00128
    • Research Site
  • Roma, Italy, 00144
    • Research Site
• Mexico
  • Mexico, Mexico, 14080
    • Research Site
  • Monterrey, Mexico, 64460
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Research Site
  • Amsterdam, Netherlands, 1081 HV
    • Research Site
  • Bergen Op Zoom, Netherlands, 4624 VT
    • Research Site
  • Den Bosch, Netherlands, 5223 GZ
    • Research Site
  • Maastricht, Netherlands, 6202 AZ
    • Research Site
• Peru
  • Lima, Peru, 15033
    • Research Site
  • Lima, Peru, L27
    • Research Site
  • Lima, Peru, LIMA 34
    • Research Site
  • Lima, Peru, LIMA 01
    • Research Site
  • Lima, Peru, LIMA 29
    • Research Site
  • Lima, Peru, LIMA 11
    • Research Site
  • Lima, Peru, 15073
    • Research Site
  • Miraflores, Peru, 15046
    • Research Site
• Poland
  • Brzozow, Poland, 36-200
    • Research Site
  • Bydgoszcz, Poland, 85-796
    • Research Site
  • Gdańsk, Poland, 80-214
    • Research Site
  • Gdańsk, Poland, 80-219
    • Research Site
  • Grudziądz, Poland, 86-300
    • Research Site
  • Kraków, Poland, 31-202
    • Research Site
  • Lubin, Poland, 59-301
    • Research Site
  • Olsztyn, Poland, 10-357
    • Research Site
  • Opole, Poland, 45-061
    • Research Site
  • Sucha Beskidzka, Poland, 34-200
    • Research Site
  • Szczecin, Poland, 70-891
    • Research Site
  • Warszawa, Poland, 02-781
    • Research Site
• Portugal
  • Amadora, Portugal, 2720-276
    • Research Site
  • Coimbra, Portugal, 3040-316
    • Research Site
  • Lisboa, Portugal, 1099-023
    • Research Site
  • Lisboa, Portugal, 1769-001
    • Research Site
  • Porto, Portugal, 4200-319
    • Research Site
  • Porto, Portugal, 4100-180
    • Research Site
  • Vila Nova de Gaia, Portugal, 4434-502
    • Research Site
• Romania
  • Cluj Napoca, Romania, 400015
    • Research Site
  • Cluj Napoca, Romania, 400058
    • Research Site
• Russian Federation
  • Kazan, Russian Federation, 420012
    • Research Site
  • Moscow, Russian Federation, 115478
    • Research Site
  • Moscow, Russian Federation, 105229
    • Research Site
  • Saint Petersburg, Russian Federation, 197342
    • Research Site
  • Saint Petersburg, Russian Federation, 197758
    • Research Site
  • Saint-Petersburg, Russian Federation, 194291
    • Research Site
  • Volgograd, Russian Federation, 400138
    • Research Site
• Spain
  • Barcelona, Spain, 08003
    • Research Site
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Madrid, Spain, 08035
    • Research Site
  • Málaga, Spain, 29010
    • Research Site
  • Sevilla, Spain, 41013
    • Research Site
  • Vigo(Pontevedra), Spain, 36204
    • Research Site
  • Zaragoza, Spain, 50009
    • Research Site
• Sweden
  • Linköping, Sweden, 581 85
    • Research Site
  • Uppsala, Sweden, SE-751 85
    • Research Site
  • Örebro, Sweden, 701 85
    • Research Site
• Turkey
  • Ankara, Turkey, 06230
    • Research Site
  • Ankara, Turkey, 06280
    • Research Site
  • Istanbul, Turkey, 34662
    • Research Site
  • Izmir, Turkey, 35100
    • Research Site
  • Izmir, Turkey, 35110
    • Research Site
  • Manisa, Turkey, 45030
    • Research Site
  • İstanbul, Turkey, 34844
    • Research Site
• Ukraine
  • Chernivtsі, Ukraine, 58013
    • Research Site
  • Dnipro, Ukraine, 49102
    • Research Site
  • Kharkiv Region, Ukraine, 61070
    • Research Site
  • Kryvyi Rih, Ukraine, 50048
    • Research Site
  • Kyiv, Ukraine, 03115
    • Research Site
  • Sumy, Ukraine, 40022
    • Research Site
  • Uzhhorod, Ukraine, 88000
    • Research Site
  • Zaporizhzhia, Ukraine, 69040
    • Research Site
• United Kingdom
  • Aberdeen, United Kingdom, AB2 2ZB
    • Research Site
  • London, United Kingdom, SW3 6JJ
    • Research Site
  • Manchester, United Kingdom, M20 4BX
    • Research Site
  • Nottingham, United Kingdom, NG5 1PB
    • Research Site
  • Sutton, United Kingdom, SM2 5PT
    • Research Site
  • Wolverhampton, United Kingdom, WV10 0QP
    • Research Site
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
  • Florida
    • Pembroke Pines, Florida, United States, 33028
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Research Site
    • Boston, Massachusetts, United States, 02215
      • Research Site
    • Danvers, Massachusetts, United States, 01923
      • Research Site
  • New York
    • New York, New York, United States, 10032
      • Research Site
    • New York, New York, United States, 10011
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Research Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19107
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Research Site
    • Nashville, Tennessee, United States, 37232
      • Research Site
  • Washington
    • Seattle, Washington, United States, 98104
      • Research Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Selumetinib; Three 25 mg selumetinib capsules (Hyd-Sulfate) be administered orally, twice daily, (total dose 75 mg dose bd) on an uninterrupted schedule.; Other Names: AZD6244; ARRY-142886; Drug: Docetaxel; Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.; 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.; Other Names: Pegfilgrastim 6 mg
Experimental: 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.	Drug: Docetaxel; Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.; 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.; Other Names: Pegfilgrastim 6 mg; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Progression free survival is defined as the time from randomisation until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression)	Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall Survival is defined as the time from the date of randomisation until death due to any cause.	Measured at baseline until date of death due to any cause. Estimated final completion : approximately 3.5 years after FSI
Objective Response Rate (ORR)	ORR is defined as the number (%) of subjects with at least one overall visit response of complete response (CR) or partial response (PR). Per RECIST v1.1 for target lesions and assessed by CT/MRI: CR - disappearance of all target lesions; PR - >=30% decrease in the sum of the longest diameter of target lesion. (Non-target lesion and new lesion results are also taken into account for the overall visit result)	Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)
Duration of Response (DoR)	Duration of response is defined as the time from the date of first documented response until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression)	Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)
Symptom Improvement Rate Using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS)	The symptom improvement rate will be defined as the number (%) of patients with two consecutive assessments at least 18 days apart (ie 21 days allowing a visit window of 3 days) which showed a clinically meaningful improvement in symptoms from baseline (defined as a decrease in the ASBI from baseline ≥10). LCSS-Lung Cancer Symptom Scale; ASBI-Average symptom burden index.	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)
Time to Symptom Progression Using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS)	Time to symptom progression will be defined as the time from randomization until the date of first clinically meaningful symptom deterioration (defined as an increase in the ASBI from baseline ≥10), or death (by any cause). LCSS-Lung Cancer Symptom Scale; ASBI-Average symptom burden index.	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)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Pasi Jänne, MD, Dana-Faber Cancer Institute, USA; Study Chair: Gabriella Mariani, MD, AstraZeneca UK, MSD

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• CSP_redacted

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2013
• Primary Completion (Actual): June 7, 2016
• Study Completion (Estimated): December 29, 2023

Study Registration Dates

• First Submitted: August 29, 2013
• First Submitted That Met QC Criteria: August 29, 2013
• First Posted (Estimated): September 2, 2013

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Mitogen-Activated Protein Kinase Kinase inhibitor; Non Small Cell Lung Cancer; metastatic; second line treatment for Non Small Cell Lung Cancer; KRAS mutation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: D1532C00079; 2013-001676-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP