AZD6244 in Combination With Docetaxel Versus Docetaxel Alone in KRAS Mutation Positive NSCLC Patients
Condition: Non Small Cell Lung Cancer
MeSH terms: Carcinoma, Non-Small-Cell Lung
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to compare the efficacy of AZD6244 in combination with docetaxel
      versus docetaxel alone in patients with KRAS mutation positive locally advanced or metastatic
      non small cell lung cancer.
    

Detailed description: 
      The primary objective of this study was to assess the efficacy in terms of overall survival
      (OS) of AZD6244 in combination with docetaxel, compared with docetaxel alone, in second-line
      patients with KRAS mutation-positive locally advanced or metastatic NSCLC. Amendment 4 of the
      CSP altered the primary objective and outcome variable from progression-free survival (PFS)
      to OS, and the secondary outcome variable changed from OS to PFS.

      The secondary objectives of the study were:

        -  To further assess the efficacy of AZD6244 in combination with docetaxel, compared with
           docetaxel alone, in second-line patients with KRAS mutation-positive locally advanced or
           metastatic NSCLC

        -  To assess the safety and tolerability profile of AZD6244 in combination with docetaxel

        -  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

        -  To investigate the PK of AZD6244 and N-desmethyl AZD6244 and any other known metabolites
           when AZD6244 is administered in combination with docetaxel.

      The exploratory objectives of the study were:

        -  To assess the prevalence, severity and change over time of advanced NSCLC cancer
           specific symptoms in patients receiving AZD6244 in combination with docetaxel and
           docetaxel alone

        -  To explore potential biomarkers in residual tumour, plasma and/or serum taken for KRAS
           mutational analysis which may influence development of NSCLC (and associated clinical
           characteristics) and/or response (optional)

        -  To investigate the relationship between AZD6244 and/or N-desmethyl AZD6244 and any other
           known metabolite plasma concentrations or exposure and clinical outcomes, efficacy, AEs,
           and/or safety parameters if deemed appropriate

        -  To collect and store deoxyribonucleic acid (DNA), derived from a blood sample, for
           future exploratory research into genes that may influence response, eg, distribution,
           safety, tolerability, and efficacy of AZD6244 and/or agents used in combination and/or
           as comparators (optional).
    

Intervention name(s): AZD6244; docetaxel; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): oral capsules, 75mg twice daily; 75mg/m2 iv on day 1 of every 21 day cycle; placebo
Other intervention name(s): Selumetinib; Taxotere
Intervention MeSH terms: Docetaxel
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Non small cell lung cancer (NSCLC); KRAS mutation