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 Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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: Cancer 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: Measured at baseline until the date of first documented objective disease progression, assessed up to approximately 3 years. ] [ Designated as safety issue: No ]
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).

Secondary Outcome Measures:

Overall Survival (OS) [ Time Frame: Measured at baseline until the date of death due to any cause, assessed up to approximately 3 years. ] [ Designated as safety issue: No ]
Overall Survival is defined as the time from the date of randomisation until death due to any cause.
Objective Response Rate (ORR) [ Time Frame: Measured at baseline until the date of first documented objective disease progression, assessed up to approximately 3 years. ] [ Designated as safety issue: No ]
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 [ Time Frame: Measured at baseline until the date of first documented objective disease progression, assessed up to approximately 3 years. ] [ Designated as safety issue: No ]
Duration of response is defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression.
Change in tumour size at week 6 [ Time Frame: At baseline and at week 6 ] [ Designated as safety issue: No ]
Percentage change from baseline in tumour size at week 6 based on RECIST 1.1 target lesion measurement.
The safety and tolerability profile of Selumetinib in Combination With Docetaxel [ Time Frame: Measured from baseline until 30 days after the date of discontinuation of the last study treatment, assessed up to approximately 3 years. ] [ Designated as safety issue: Yes ]
The safety and tolerability profile of Selumetinib in Combination With Docetaxel will be assessed using adverse events, clinical chemistry, haematology and urinalysis, vital signs, ECGs and echocardiograms/MUGA, ophthalmological examination.
Correlation of KRAS mutation status with efficacy of treatment [ Time Frame: Measured from date of randomisation until the date of first documented objective disease progression, assessed up to approximately 3 years. ] [ Designated as safety issue: No ]
Efficacy will be assessed within KRAS mutation subgroups in terms of PFS, OS, ORR and change in tumour size at week 6. KRAS: v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog
The effect on health-related quality of life (HRQoL) [ Time Frame: Measured from baseline until the date of discontinuation of study treatment, assessed up to approximately 3 years. ] [ Designated as safety issue: No ]
The effect of HRQoL will be assessed using the summary items of the LCSS-Lung Cancer Symptom Scale (symptom distress, interference with activity levels and global HRQoL); the average LCSS score (the mean of all 9 items of the LCSS); the scores for each of the 8 health domain scales as well as the 2 summary measures of the SF-36v2 (Short Form Health Survey - 36 Items (Version 2)).
The pharmacokinetics (PK) of selumetinib and N-desmethyl selumetinib measured by AUC, Cmax. [ Time Frame: PK samples taken on day 22 ] [ Designated as safety issue: No ]
The pharmacokinetics (PK) of selumetinib and N-desmethyl selumetinib when administered in combination with docetaxel measured by derived PK parameters, such as AUC and Cmax.

AUC: Area under plasma concentration time curve
Symptom improvement rate (using ASBI from LCSS) [ Time Frame: Measured from date of randomisation until 30 days post treatment discontinuation, assessed up to approximately 3 years. ] [ Designated as safety issue: No ]
The symptom improvement rate will be defined as the number (%) of patients with two consecutive assessments at least 18 days apart (ie 21 days allowing a visit window of 3 days) which showed a clinically meaningful improvement in symptoms from baseline (defined as a decrease in the ASBI from baseline ≥10). LCSS-Lung Cancer Symptom Scale; ASBI-Average symptom burden index.
Time to symptom progression (using ASBI from LCSS) [ Time Frame: Measured from date of randomisation until 30 days post treatment discontinuation, assessed up to approximately 3 years. ] [ Designated as safety issue: No ]
Time to symptom progression will be defined as the time from randomization until the date of first clinically meaningful symptom deterioration (defined as an increase in the ASBI from baseline ≥10), or death (by any cause). LCSS-Lung Cancer Symptom Scale; ASBI-Average symptom burden index.


Enrollment:	466
Study Start Date:	December 2012
Estimated Study Completion Date:	December 2016
Primary Completion Date:	January 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)
Genders Eligible for Study:	Both
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
Study First Received:	December 12, 2012
Last Updated:	August 31, 2016
Health Authority:	United States: Food and Drug Administration France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices Hungary: National Institute of Pharmacy Brazil: National Health Surveillance Agency Brazil: National Committee of Ethics in Research Bulgaria: Bulgarian Drug Agency Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

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 23, 2016

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