Locally Advanced or Metastatic Non Small Cell Lung Cancer stage IIIb - IV
Conditions
Interventions
Product Name: Selumetinib
Product Code: AZD6244 blue 25 mg capsule
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: selumetinib
CAS Number: 943332-08-9
Current Sponsor code: AZD6244 Hydrogen Su
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 190 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 444
Exclusion criteria
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. Any systemic anti-cancer therapy within 4 weeks prior to starting study treatment (6 weeks for nitrosoureas, mitomycin, and suramin) or any anti-cancer therapy which has not been cleared from the body by the time of starting study treatement Prior treatment with a MEK inhibitor or any docetaxel-containing regimen (prior treatment with paclitaxel is acceptable)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy in terms of Progression-Free-Survival (PFS) of selumetinib in combination with docetaxel, compared to placebo in combination with docetaxel PFS using investigator site assessments according to RECIST 1.1 ;Secondary Objective: To assess the efficacy of selumetinib in combination with docetaxel, compared with placebo in combination with docetaxel in terms of - OS - ORR using investigator site assessments according to RECIST 1.1 - DoR using investigator site assessments according to RECIST 1.1 To assess the efficacy of selumetinib in combination with docetaxel compared with placebo in combination with docetaxel on NSCLC symptoms. ASBI of the six symptoms (appetite, fatigue, coughing, shortness of breath, blood in sputum and pain) in the LCSS will be used to assess: Time to symptom progression and Symptom improvement rate To assess the safety and tolerability profile of selumetinib in combination with docetaxel compared with placebo in combination in terms of AEs, Clinical chemistry, haematology and urinalysis, Vital signs and ECHO/MUGA To investigate the PK of selumetinib and N-desmethyl selumetinib when administered in combination with docetaxel (other selumetinib metabolites may also be assessed);Primary end point(s): Progression-Free Survival (PFS) 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). ;Timepoint(s) of evaluation of this end point: Measured at baseline until the date of first documented objective disease progression, assessed up to 33 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Survival (OS) Overall Survival is defined as the time from the date of randomisation until death due to any cause. Objective Response Rate (ORR) 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 (DoR) 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. Symptom improvement rate (using ASBI from LCSS) Time to symptom progression (using ASBI from LCSS) The safety and tolerability profie of Selumetinib in Combination with Docetaxel by assessing of adverse events, Clinical chemistry, haematology and urinalysis, vital signs, ECG and Echocardiogram The pharmacokinetics (PK) of selumetinib and N-desmethyl selumetinib when administered in combination with docetaxel by assessment of area under plasma concentration time curve (AUC + Cmax);Timepoint(s) of evaluation of this end point: Overall Survival (OS) Measured at baseline until date of death due to any cause, assessed up to 41 months Objective Response Rate (ORR) Measured at baseline until the date of first documented objective disease progression, assessed up to 33 months Symptom improvement rate (using ASBI from LCSS); Measured from date of randomisation until 30 days post treatment discontinuation, assessed up to 33 months Time to symptom progression (using ASBI from LCSS); Measured from date of randomisation until 30 days post treatment discontinuation, assessed up to 33 months. The safety and tolerability profie of Selumetinib in Combination with Docetaxel; Measured from date of randomisation until 30 days post treatment discontinuation, assessed up to 33 months PK samples will be taken on day 22 | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, France, Germany, Hungary, Israel, Italy, Mexico, Netherlands, Poland, Portugal, Romania, Russian Federation, Spain, Sweden, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactInformation Centre
AstraZeneca
Outcome results
None listed