Assess Efficacy and Safety of AZD6244 in Combination With Docetaxel in Patients Receiving Second Line Non Small Cell Lung Cancer Treatment. (SELECT-2)

A Phase II, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy and Safety of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Combination With Docetaxel, Compared With Placebo in Combination With Docetaxel, in Patients Receiving Second Line Treatment for Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB - IV)

The purpose of this study is to treat patients with locally advanced or metastatic NSCLC with a combination therapy of selumetinib and two different doses of docetaxel 75mg/m2 or 60 mg/m2 vs placebo and compare how well each dose affects how their cancer responds. It will also help us to understand the tolerability profile of the different dosing regimens in these patients

Study Overview

• Status: Completed
• Conditions: Locally Advanced or Metastatic Non Small Cell Lung Cancer Stage IIIb - IV
• Intervention / Treatment: Drug: Selumetinib 75 mg; Drug: Docetaxel 75 mg/m2; Drug: Docetaxel 60 mg/m2; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 212
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Barretos, Brazil, 14784-400
    • Research Site
  • Brasilia, Brazil, 70390-055
    • Research Site
  • Ijuí, Brazil, 98700-000
    • Research Site
  • Porto Alegre, Brazil, 90035-003
    • Research Site
  • Porto Alegre, Brazil, 91350-200
    • Research Site
  • Porto Alegre, Brazil, 90619-900
    • Research Site
  • Santo André, Brazil, 09060-650
    • Research Site
  • Sao Paulo, Brazil, 01246-000
    • Research Site
  • Sao Paulo, Brazil, 01221-020
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Research Site
  • São Paulo, Brazil, 04039-002
    • Research Site
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • Research Site
  • Plovdiv, Bulgaria, 4004
    • Research Site
  • Sofia, Bulgaria, 1233
    • Research Site
  • Sofia, Bulgaria, 1756
    • Research Site
  • Sofia, Bulgaria, 1330
    • Research Site
  • Sofia, Bulgaria, 1303
    • Research Site
  • Varna, Bulgaria, 9010
    • Research Site
  • Vratza, Bulgaria, 3000
    • Research Site
• France
  • Brest Cedex, France, 29609
    • Research Site
  • Caen, France, F-14033
    • Research Site
  • Clermont Ferrand, France, 63003
    • Research Site
  • Lille, France, 59000
    • Research Site
  • Pierre Benite Cedex, France, 69310
    • Research Site
  • Villejuif, France, 94805
    • Research Site
• Germany
  • Essen, Germany, 45122
    • Research Site
  • Esslingen, Germany, 73730
    • Research Site
  • Großhansdorf, Germany, 22927
    • Research Site
  • Karlsruhe, Germany, 76137
    • Research Site
  • Löwenstein, Germany, 74245
    • Research Site
  • Moers, Germany, 47441
    • Research Site
  • Wiesbaden, Germany, 65199
    • Research Site
  • Würzburg, Germany, 97080
    • Research Site
• Hungary
  • Budapest, Hungary, 1121
    • Research Site
  • Budapest, Hungary, 1122
    • Research Site
  • Budapest, Hungary, 1032
    • 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
  • Székesfehérvár, Hungary, 8000
    • Research Site
  • Törökbálint, Hungary, 2045
    • 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
• Poland
  • Gdańsk, Poland, 80-219
    • Research Site
  • Grudziądz, Poland, 86-300
    • Research Site
  • Kraków, Poland, 31-202
    • Research Site
  • Olsztyn, Poland, 10-357
    • Research Site
  • Poznań, Poland, 61-848
    • Research Site
  • Sucha Beskidzka, Poland, 34-200
    • Research Site
  • Szczecin, Poland, 70-891
    • Research Site
• United States
  • California
    • Santa Monica, California, United States, 90404
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
  • Florida
    • Hollywood, Florida, United States, 33028
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • New York
    • Mineola, New York, United States, 11501
      • Research Site
    • New York, New York, United States, 10032
      • Research Site
    • New York, New York, United States, 10011
      • Research Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19107
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • 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)
• Prospective confirmation of KRAS mutation negative status as determined via an AZ approved 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.
• Other concomitant anti-cancer therapy agents except steroids
• Prior treatment with a MEK (Mitogen-Activated Protein Kinase) inhibitor or any docetaxel-containing regimen (prior treatment with paclitaxel is acceptable)
• The last radiation therapy within 4 weeks prior to 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Selumetinib 75 mg twice daily +Docetaxel 75 mg/m2; 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 75 mg; Three selumetinib capsules (Hyd-Sulfate) 25 mg will be administered orally, twice daily, (75 mg dose bd) on an uninterrupted schedule.; Drug: Docetaxel 75 mg/m2; Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.
Experimental: Selumetinib 75 mg twice daily + Docetaxel 60 mg/m2; Selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 60 mg/m2 intravenously administered on day 1 of each 21 day cycle.	Drug: Selumetinib 75 mg; Three selumetinib capsules (Hyd-Sulfate) 25 mg will be administered orally, twice daily, (75 mg dose bd) on an uninterrupted schedule.; Drug: Docetaxel 60 mg/m2; Docetaxel 60 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.
Experimental: Placebo twice daily + Docetaxel 75 mg/m2; 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 75 mg/m2; Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.; Drug: Placebo; Three placebo capsules will be administered orally uninterrupted twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Median time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined using Response Evaluation Criteria in Solid Tumours (RECIST v1.1): >= 20% increase in the sum of diameters of Target Lesions (TL) and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of Non TLs or a new lesion.	Baseline and then every 6 weeks after randomization until objective disease progression, up to 29 months (at the time of the analysis)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	The time from randomisation until death due to any cause. Any subject not known to have died at the time of analysis will be censored based on the last recorded date on which the subject was known to be alive	Following progression, survival status was collected every 8 weeks until death, withdrawal of consent, or end of study, whichever occurred first, up to 29 months (at the time of the analysis)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Pasi Janne, MD, Dana-Farber Cancer Institute, USA; Principal Investigator: Jean-Charles Soria, MD, Institut de Cancerology Gustave Roussy, France; Study Chair: Gabriella Mariani, MD, AstraZeneca UK, MSD

Publications and helpful links

General Publications

• Soria JC, Fulop A, Maciel C, Fischer JR, Girotto G, Lago S, Smit E, Ostoros G, Eberhardt WEE, Lishkovska P, Lovick S, Mariani G, McKeown A, Kilgour E, Smith P, Bowen K, Kohlmann A, Carlile DJ, Janne PA. SELECT-2: a phase II, double-blind, randomized, placebo-controlled study to assess the efficacy of selumetinib plus docetaxel as a second-line treatment of patients with advanced or metastatic non-small-cell lung cancer. Ann Oncol. 2017 Dec 1;28(12):3028-3036. doi: 10.1093/annonc/mdx628.

Helpful Links

• CSR Synopsis Redacted

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2012
• Primary Completion (Actual): January 27, 2016
• Study Completion (Actual): October 31, 2022

Study Registration Dates

• First Submitted: December 12, 2012
• First Submitted That Met QC Criteria: December 13, 2012
• First Posted (Estimated): December 17, 2012

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 12, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Non Small Cell Lung Cancer; Metastatic; Mitogen-Activated Protein Kinase Kinase inhibitor; Second line treatment for Non Small Cell Lung Cancer
• 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: D1532C00064; 2012-003622-25 (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