Overview

This trial is active, not recruiting.

Condition locally advanced or metastatic non small cell lung cancer stage iiib - iv
Treatments selumetinib 75 mg, docetaxel 75 mg/m2, docetaxel 60 mg/m2, placebo
Phase phase 2
Target MEK
Sponsor AstraZeneca
Start date December 2012
End date January 2016
Trial size 466 participants
Trial identifier NCT01750281, 2012-003622-25, D1532C00064

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
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.
selumetinib 75 mg
Three selumetinib capsules (Hyd-Sulfate) 25 mg will be administered orally, twice daily, (75 mg dose bd) on an uninterrupted schedule.
docetaxel 75 mg/m2
Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.
(Experimental)
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.
selumetinib 75 mg
Three selumetinib capsules (Hyd-Sulfate) 25 mg will be administered orally, twice daily, (75 mg dose bd) on an uninterrupted schedule.
docetaxel 60 mg/m2
Docetaxel 60 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.
(Experimental)
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.
docetaxel 75 mg/m2
Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.
placebo
Three placebo capsules will be administered orally uninterrupted twice daily.

Primary Outcomes

Measure
Progression-Free Survival (PFS)
time frame: Measured at baseline until the date of first documented objective disease progression, assessed up to approximately 3 years.

Secondary Outcomes

Measure
Overall Survival (OS)
time frame: Measured at baseline until the date of death due to any cause, assessed up to approximately 3 years.
Objective Response Rate (ORR)
time frame: Measured at baseline until the date of first documented objective disease progression, assessed up to approximately 3 years.
Duration of Response
time frame: Measured at baseline until the date of first documented objective disease progression, assessed up to approximately 3 years.
Change in tumour size at week 6
time frame: At baseline and at week 6
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.
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.
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.
The pharmacokinetics (PK) of selumetinib and N-desmethyl selumetinib measured by AUC, Cmax.
time frame: PK samples taken on day 22
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.
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.

Eligibility Criteria

Male or female participants from 18 years up to 130 years old.

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.

Additional Information

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)
Principal investigator Pasi Janne, MD
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)
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by AstraZeneca.