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

Purpose

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

Condition	Intervention	Phase
Locally Advanced or Metastatic Non Small Cell Lung Cancer Stage IIIb - IV	Drug: Selumetinib 75 mg Drug: Docetaxel 75 mg/m2 Drug: Docetaxel 60 mg/m2 Drug: Placebo	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	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)

Resource links provided by NLM:

Genetics Home Reference related topics: lung cancer

MedlinePlus related topics: Lung Cancer

Drug Information available for: Docetaxel

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

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 Outcome Measures:

Overall Survival (OS) [ Time Frame: 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) ]
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


Enrollment:	212
Actual Study Start Date:	December 18, 2012
Estimated Study Completion Date:	December 29, 2017
Primary Completion Date:	January 27, 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 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.	Drug: Selumetinib 75 mg Three selumetinib capsules (Hyd-Sulfate) 25 mg will be administered orally, twice daily, (75 mg dose bd) on an uninterrupted schedule. Drug: Docetaxel 75 mg/m2 Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.
Experimental: 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.	Drug: Selumetinib 75 mg Three selumetinib capsules (Hyd-Sulfate) 25 mg will be administered orally, twice daily, (75 mg dose bd) on an uninterrupted schedule. Drug: Docetaxel 60 mg/m2 Docetaxel 60 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.
Experimental: 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.	Drug: Docetaxel 75 mg/m2 Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle. Drug: Placebo Three placebo capsules will be administered orally uninterrupted twice daily.

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)

Eligibility


Ages Eligible for Study:	18 Years to 130 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01750281

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Sponsors and Collaborators

AstraZeneca

Investigators


Study Chair:	Gabriella Mariani, MD	AstraZeneca UK, MSD
Principal Investigator:	Pasi Janne, MD	Dana-Farber Cancer Institute, USA
Principal Investigator:	Jean-Charles Soria, MD	Institut de Cancerology Gustave Roussy, France

More Information


Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01750281 History of Changes
Other Study ID Numbers:	D1532C00064 2012-003622-25 ( EudraCT Number )
Study First Received:	December 12, 2012
Results First Received:	January 13, 2017
Last Updated:	June 21, 2017

Keywords provided by AstraZeneca:


Mitogen-Activated Protein Kinase Kinase inhibitor Non Small Cell Lung Cancer Metastatic Second line treatment for Non Small Cell Lung Cancer

Additional relevant MeSH terms:


Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases	Carcinoma, Bronchogenic Bronchial Neoplasms Docetaxel Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 21, 2017

Assess Efficacy and Safety of AZD6244 in Combination With Docetaxel in Patients Receiving Second Line Non Small Cell Lung Cancer Treatment. (SELECT-2)