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

• Progression-Free Survival (PFS) [ Time Frame: Measured at baseline until the date of first documented objective disease progression, assessed up to 16 months. ] [ Designated as safety issue: No ]
  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).
  
  

• Overall Survival (OS) [ Time Frame: Measured at baseline until the date of death due to any cause, assessed up to 16 months. ] [ Designated as safety issue: No ]
  Overall Survival is defined as the time from the date of randomisation until death due to any cause.
  
  
• Objective Response Rate (ORR) [ Time Frame: Measured at baseline until the date of first documented objective disease progression, assessed up to 16 months. ] [ Designated as safety issue: No ]
  ORR is defined as the number (%) of subjects with at least one visit response of complete response (CR) or partial response (PR).
  
  
• Duration of Response [ Time Frame: Measured at baseline until the date of first documented objective disease progression, assessed up to 16 months. ] [ Designated as safety issue: No ]
  Duration of response will be defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression.
  
  
• Change in tumour size at week 6 [ Time Frame: At baseline and at week 6 ] [ Designated as safety issue: No ]
  Percentage change from baseline in tumour size at week 6 based on RECIST 1.1 target lesion measurement.
  
  
• The safety and tolerability profile of Selumetinib in Combination With Docetaxel [ Time Frame: Measured from baseline until 30 days after the date of discontinuation of the last study treatment, assessed up to 16 months. ] [ Designated as safety issue: Yes ]
  The safety and tolerability profile of Selumetinib in Combination With Docetaxel will be assessed using adverse events, clinical chemistry, haematology and urinalysis, vital signs, ECGs and echocardiograms.
  
  
• Correlation of KRAS mutation status with efficacy of treatment [ Time Frame: Measured from date of randomisation until the date of first documented objective disease progression, assessed up to 16 months. ] [ Designated as safety issue: No ]

  Efficacy will be assessed within KRAS mutation subgroups in terms of PFS, OS, ORR and change in tumour size at week 6.

  KRAS: v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog

  
  
• The effect on health-related quality of life (HRQoL) [ Time Frame: Measured from baseline until the date of discontinuation of study treatment, assessed up to 16 months. ] [ Designated as safety issue: No ]
  The effect of HRQoL will be assessed using the summary items of the LCSS-Lung Cancer Symptom Scale (symptom distress, interference with activity levels and global HRQoL); the average LCSS score (the mean of all 9 items of the LCSS); the scores for each of the 8 health domain scales as well as the 2 summary measures of the SF-36v2 (Short Form Health Survey - 36 Items (Version 2)).
  
  
• The pharmacokinetics (PK) of selumetinib and N-desmethyl selumetinib measured by AUC, Cmax. [ Time Frame: PK samples taken on day 22 ] [ Designated as safety issue: No ]

  The pharmacokinetics (PK) of selumetinib and N-desmethyl selumetinib when administered in combination with docetaxel measured by derived PK parameters, such as AUC and Cmax.

  AUC: Area under plasma concentration time curve

  
  
• Symptom improvement rate (using ASBI from LCSS) [ Time Frame: Measured from date of randomisation until 30 days post treatment discontinuation, assessed up to 16 months. ] [ Designated as safety issue: No ]
  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.
  
  
• Time to symptom progression (using ASBI from LCSS) [ Time Frame: Measured from date of randomisation until 30 days post treatment discontinuation, assessed up to 16 months. ] [ Designated as safety issue: No ]
  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.
  
  

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)