Assess Safety & Efficacy of Selumetinib When Given in Combination With Standard First Line Treatment for Advanced Non-small Cell Lung Cancer
Condition: Locally Advanced or Metastatic NSCL Cancer Stage IIIB IV
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: selumetinib; gemcitabine; cisplatin; carboplatin; pemetrexed
Intervention description: 2 x 25mg capsules bd continuously in cohort 1 (with gemcitabine and cisplatin). If tolerated - next cohort 3 x 25mg capsules bd continuously. if higher doses are explored, required number of capsules will be provided. Option to administer on D2-19 of each 21 day cycle if required to assess tolerability of combinations with chemotherapy; 1250 mg/m2 iv on Day 1 and 8 of each 21 day cycle. If combination not tolerated, option to give 1000 mg/m2 iv on Day 1 and Day 8 of each 21 day cycle; 75 mg/m2 iv on Day 1 of each 21 day cycle. If combination not tolerated, option to give 50 mg/m2 iv on Day 1 or 25mg/m2 iv on Day 1 and Day 8 of each 21 day cycle; If it is not possible to identify a tolerable combination of selumetinib, gemcitabine and cisplatin, cisplatin may be replaced with carboplatin (AUC5) iv on Day 1 of each 21 day cycle; Gemcitabine may be replaced with pemetrexed 500 mg/m2 iv on Day 1 of each 21 day cycle.
Intervention MeSH terms: Carboplatin; Gemcitabine; Pemetrexed
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 55.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: MEK1/2 inhibitor,; Non Small Cell Lung Cancer,; metastatic,; first line treatment for Non Small Cell Lung Cancer

Summary:

      This is a Phase I, open label multicentre study of selumetinib administered orally in
      combination with first line chemotherapy regimens to patients with advanced/metastatic NSCLC.
      The study has been designed to allow an investigation of the optimal dose of selumetinib in
      combination with various standard first line double-platinum chemotherapy regimens. Initial
      assessment will be based on tolerability of selumetinib in combination with one or more
      selected regimens that are considered to be tolerated also being assessed for preliminary
      evidence of activity.

      This study is a dose finding and optional cohort expansion; In addition all patients will be
      assessed for anti-cancer efficacy of the combination of selumetinib and chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provision of signed, written and dated 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)

          -  Female patients must not be breast-feeding and have a negative pregnancy test prior to
             start of dosing or must have evidence of non-child-bearing potential

          -  Patients must be eligible to receive treatment with the platinum doublet combination
             with which selumetinib is being combined and in accordance with the local product
             information

        Exclusion Criteria:

          -  Prior chemotherapy or other systemic anti-cancer treatment for advanced NSCLC.

          -  Prior surgery or radiotherapy within 6 months or palliative radiotherapy within 4
             weeks of start of study treatment.

          -  Female patients who are breast-feeding or male or female patients of reproductive
             potential who are not employing an effective method of birth control

          -  Another primary malignancy within 5 years of starting study treatment, except for
             adequately treated basal or squamous cell carcinoma of the skin or cancer of the
             cervix in situ.

          -  As judged by the Investigator, any evidence of severe or uncontrolled systemic
             diseases, active bleeding diatheses, renal transplant, or active infection