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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

NCT01933932

Description:

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

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: D1532C00079
  • SECONDARY ID: 2013-001676-38
  • NCT ID: NCT01933932

Conditions

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

Interventions

DrugSynonymsArms
SelumetinibAZD6244; ARRY-142886Selumetinib + Docetaxel
DocetaxelSelumetinib + Docetaxel
PlaceboPlacebo + Docetaxel
Pegylated G-CSFPegfilgrastim 6 mgSelumetinib + Docetaxel

Purpose

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)
    

Trial Arms

NameTypeDescriptionInterventions
Selumetinib + DocetaxelExperimentalThree 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
  • Selumetinib
  • Docetaxel
  • Pegylated G-CSF
Placebo + DocetaxelExperimentalThree 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.
  • Docetaxel
  • Placebo
  • Pegylated G-CSF

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
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS)
Time Frame:Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)
Safety Issue:
Description: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)

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Measured at baseline until date of death due to any cause. Estimated final completion : approximately 3.5 years after FSI
Safety Issue:
Description:Overall Survival is defined as the time from the date of randomisation until death due to any cause.
Measure:Objective Response Rate (ORR)
Time Frame:Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)
Safety Issue:
Description: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)
Measure:Duration of Response (DoR)
Time Frame:Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)
Safety Issue:
Description: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)
Measure:Symptom Improvement Rate Using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS)
Time Frame: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)
Safety Issue:
Description: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.
Measure:Time to Symptom Progression Using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS)
Time Frame: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)
Safety Issue:
Description: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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Mitogen-Activated Protein Kinase Kinase inhibitor; Non Small Cell Lung Cancer; metastatic; second line treatment for Non Small Cell Lung Cancer; KRAS mutation

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