D1532C00016: a Phase II, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy of AZD6244 (Hyd-Sulfate) in Combination with Docetaxel, Compared with Docetaxel Alone, in 2nd Line Patients with KRAS Mutation Positive Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB - IV)

INTERVENTION: Product Name: AZD6244 Product Code: AZD6244 Pharmaceutical Form: Capsule, hard CAS Number: 606143‐52‐6 Current Sponsor code: AZD6244 Other descriptive name: AZD6244 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Product Name: docetaxel Pharmaceutical Form: Concentrate and solvent for solution for injection INN or Proposed INN: docetaxel CAS Number: 114977‐28‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20‐ INN or Proposed INN: docetaxel CAS Number: 114977‐28‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 80‐ CONDITION: 2nd Line Patients with KRAS Mutation Positive Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB – IV) ; MedDRA version: 9.1 Level: LLT Classification code 10029521 Term: Non‐small cell lung cancer stage IIIB ; MedDRA version: 9.1 Level: LLT Classification code 10029522 Term: Non‐small cell lung cancer stage IV ; MedDRA version: 9.1 Level: LLT Classification code 10059515 Term: Non‐small cell lung cancer metastatic PRIMARY OUTCOME: Main Objective: To assess the efficacy in terms of progression free survival of AZD6244 in combination with docetaxel, compared with docetaxel alone, in 2nd line patients with KRAS mutation positive locally advanced or metastatic NSCLC Primary end point(s): Progression free survival Secondary Objective: 1) To further assess the efficacy of AZD6244 (in terms of overall survival, objective response rate, duration of response, change in tumour size at 12 weeks and alive and progression free at 6 months) in combination with docetaxel, compared with docetaxel alone, in 2nd line patients with KRAS mutation positive locally advanced or metastatic NSCLC.; 2) To assess the safety and tolerability profile of AZD6244 in combination with docetaxel.; 3) To investigate the use of plasma and serum as a potential source of circulating free tumour DNA (CFDNA) for the analysis of KRAS mutation status.; 4) To investigate the pharmacokinetics (PK) of AZD6244 and N‐desmethyl AZD6244 and any other known metabolites when AZD6244 is administered in combination with docetaxel. INCLUSION CRITERIA: 1. Provision of signed, written and dated informed consent prior to any study specific procedures. 2. Male or female, aged 18 years or older. 3. Histological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB‐IV). 4. Failure of 1st line anti‐cancer therapy (either radiological documentation of disease progression or due to toxicity) in advanced disease or subsequent relapse of disease following 1st line therapy. See Appendix L of the protocol for further details. See Section 5.2 of the protocol for specific 1st line agents not permitted in this study. 5. WHO Performance Status 0 – 1. 6. Patients must be eligible to receive treatment with docetaxel in accordance with docetaxel product information (available from Sanofi‐Aventis, the manufacturer of docetaxel – see Appendix J of the protocol for contact details). 7. At least one lesion, not previously irradiated, that can be accurately measured as =10 mm in the longest dia