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)
Overview
- Phase
- Phase 2
- Intervention
- Selumetinib 75 mg
- Conditions
- Locally Advanced or Metastatic Non Small Cell Lung Cancer Stage IIIb - IV
- Sponsor
- AstraZeneca
- Enrollment
- 212
- Locations
- 1
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of this study is to treat patients with locally advanced or metastatic NSCLC with a combination therapy of selumetinib and two different doses of docetaxel 75mg/m2 or 60 mg/m2 vs placebo and compare how well each dose affects how their cancer responds. It will also help us to understand the tolerability profile of the different dosing regimens in these patients
Detailed Description
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)
Investigators
Eligibility 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)
- •Prospective confirmation of KRAS mutation negative status as determined via an AZ approved 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
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.
- •Other concomitant anti-cancer therapy agents except steroids
- •Prior treatment with a MEK (Mitogen-Activated Protein Kinase) inhibitor or any docetaxel-containing regimen (prior treatment with paclitaxel is acceptable)
- •The last radiation therapy within 4 weeks prior to starting study treatment, or limited field of radiation for palliation within 7 days of the first dose of study treatment.
Arms & Interventions
Selumetinib 75 mg twice daily +Docetaxel 75 mg/m2
Selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.
Intervention: Selumetinib 75 mg
Selumetinib 75 mg twice daily +Docetaxel 75 mg/m2
Selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.
Intervention: Docetaxel 75 mg/m2
Selumetinib 75 mg twice daily + Docetaxel 60 mg/m2
Selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 60 mg/m2 intravenously administered on day 1 of each 21 day cycle.
Intervention: Selumetinib 75 mg
Selumetinib 75 mg twice daily + Docetaxel 60 mg/m2
Selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 60 mg/m2 intravenously administered on day 1 of each 21 day cycle.
Intervention: Docetaxel 60 mg/m2
Placebo twice daily + Docetaxel 75 mg/m2
Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.
Intervention: Docetaxel 75 mg/m2
Placebo twice daily + Docetaxel 75 mg/m2
Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.
Intervention: Placebo
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: Baseline and then every 6 weeks after randomization until objective disease progression, up to 29 months (at the time of the analysis)
Median time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined using Response Evaluation Criteria in Solid Tumours (RECIST v1.1): \>= 20% increase in the sum of diameters of Target Lesions (TL) and an absolute increase in sum of diameters of \>=5mm (compared to the previous minimum sum) or progression of Non TLs or a new lesion.
Secondary Outcomes
- Overall Survival (OS)(Following progression, survival status was collected every 8 weeks until death, withdrawal of consent, or end of study, whichever occurred first, up to 29 months (at the time of the analysis))