Assess Efficacy and Safety of AZD6244 in Combination With Docetaxel in Patients Receiving Second Line Non Small Cell Lung Cancer Treatment.

Study Overview
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Brief Summary
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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
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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)

Official Title
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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)

Conditions
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Locally Advanced or Metastatic Non Small Cell Lung Cancer Stage IIIb - IV

Intervention / Treatment
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* Drug: Selumetinib 75 mg
* Drug: Docetaxel 75 mg/m2
* Drug: Docetaxel 60 mg/m2
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selumetinib 75 mg twice daily +Docetaxel 75 mg/m2<br>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. | Drug: Selumetinib 75 mg<br>* Three selumetinib capsules (Hyd-Sulfate) 25 mg will be administered orally, twice daily, (75 mg dose bd) on an uninterrupted schedule.<br>Drug: Docetaxel 75 mg/m2<br>* Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.<br>|
| Experimental: Selumetinib 75 mg twice daily + Docetaxel 60 mg/m2<br>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. | Drug: Selumetinib 75 mg<br>* Three selumetinib capsules (Hyd-Sulfate) 25 mg will be administered orally, twice daily, (75 mg dose bd) on an uninterrupted schedule.<br>Drug: Docetaxel 60 mg/m2<br>* Docetaxel 60 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.<br>|
| Experimental: Placebo twice daily + Docetaxel 75 mg/m2<br>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. | Drug: Docetaxel 75 mg/m2<br>* Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.<br>Drug: Placebo<br>* Three placebo capsules will be administered orally uninterrupted twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | 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. | Baseline and then every 6 weeks after randomization until objective disease progression, up to 29 months (at the time of the analysis) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | The time from randomisation until death due to any cause. Any subject not known to have died at the time of analysis will be censored based on the last recorded date on which the subject was known to be alive | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mitogen-Activated Protein Kinase Kinase inhibitor, Non Small Cell Lung Cancer, Metastatic, Second line treatment for Non Small Cell Lung Cancer