Overview

This trial is active, not recruiting.

Condition locally advanced or metastatic non small cell lung cancer stage iiib - iv
Treatments selumetinib, docetaxel, placebo, pegylated g-csf
Phase phase 3
Target MEK
Sponsor AstraZeneca
Start date September 2013
End date June 2016
Trial size 3332 participants
Trial identifier NCT01933932, 2013-001676-38, D1532C00079

Summary

The purpose of this study is to assess the efficacy of selumetinib in combination with docetaxel (75mg/m2) vs placebo in combination with docetaxel (75mg/m2) in patients with locally advance or metastatic NSCLCs that harbor mutations of KRAS. This study will also assess the PK, safety, patient reported outcomes (PRO) and tolerability profile of the selumetinib/docetaxel combination, compared to placebo in combination with docetaxel

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Three 25mg 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 AZD6244; ARRY-142886
Three 25 mg selumetinib capsules (Hyd-Sulfate) be administered orally, twice daily, (total dose 75 mg dose bd) on an uninterrupted schedule.
docetaxel
Docetaxel 75 mg/m2 will be administered intravenously on day 1 of each 21 day cycle.
pegylated g-csf Pegfilgrastim 6 mg
All patients will receive pegylated Granulocyte Colony Stimulating Factor (G-CSF) at least 24 hours after administration of every docetaxel dose and not within 14 days prior to the next docetaxel administration.
(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
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 in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.
pegylated g-csf Pegfilgrastim 6 mg
All patients will receive pegylated Granulocyte Colony Stimulating Factor (G-CSF) at least 24 hours after administration of every docetaxel dose and not within 14 days prior to the next docetaxel administration.

Primary Outcomes

Measure
Progression-Free Survival (PFS)
time frame: Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)

Secondary Outcomes

Measure
Overall Survival (OS)
time frame: Measured at baseline until date of death due to any cause. Estimated final completion : approximately 3.5 years after FSI
Objective Response Rate (ORR)
time frame: Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)
Duration of Response (DoR)
time frame: Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)
Symptom improvement rate using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS)
time frame: Measured from date of randomisation until 30 days post treatment discontinuation or 30 days post progression (if study treatment is discontinued before progression). Estimated final completion : approximately 3 years after first subject in (FSI)
Time to symptom progression using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS)
time frame: Measured from date of randomisation until 30 days post treatment discontinuation or 30 days post progression (if study treatment is discontinued before progression). Estimated final completion : approximately 3 years after first subject in (FSI)
Investigate safety and tolerability profile of Selumetinib in combination with docetaxel compared with placebo in combination with docetaxel by assessing of frequency of adverse events
time frame: Measured from baseline until 30 days after the date of discontinuation of the last study treatment. Estimated final completion : approximately 3 years after first subject in (FSI)
Investigate safety and tolerability profile of Selumetinib in combination with docetaxel compared with placebo in combination with docetaxel by assessing laboratory variables
time frame: Measured from baseline until 30 days after the date of discontinuation of the last study treatment. Estimated final completion : approximately 3 years after first subject in (FSI)
Investigate safety and tolerability profile of Selumetinib in combination with docetaxel compared with placebo in combination with docetaxel by assessing vital signs
time frame: Measured from baseline until 30 days after the date of discontinuation of the last study treatment. Estimated final completion : approximately 3 years after first subject in (FSI)
Investigate safety and tolerability profile of Selumetinib in combination with docetaxel compared with placebo in combination with docetaxel by assessing Echocardiogram (ECHO) / Multi Gated Acquisition (MUGA) scan
time frame: Measured from baseline until 30 days after the date of discontinuation of the last study treatment. Estimated final completion : approximately 3 years after first subject in (FSI)
Investigate safety and tolerability profile of Selumetinib in combination with docetaxel compared with placebo in combination with docetaxel by assessing Opthalmological examinations
time frame: Measured from baseline until 30 days after the date of discontinuation of the last study treatment. Estimated final completion : approximately 3 years after first subject in (FSI)
Investigate the pharmacokinetics (PK) of selumetinib and N-desmethyl selumetinib when administered in combination with docetaxel by assessing the area under plasma concentration time curve (AUC)
time frame: PK blood samples will be collected pre-dose and up to 8 hours post-dose on day 1 and day 22. Estimated final completion : approximately 3 years after first subject in (FSI)
Investigate the pharmacokinetics (PK) of selumetinib and N-desmethyl selumetinib when administered in combination with docetaxel by assessing Cmax
time frame: PK blood samples will be collected pre-dose and up to 8 hours post-dose on day 1 and day 22. Estimated final completion : approximately 3 years after first subject in (FSI)

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) - KRAS mutation positive tumour sample as determined by the designated testing 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. - Receiving or have received systemic anti-cancer therapy within 30 days prior to starting study treatment - Other concomitant anti-cancer therapy agents excepts steroids - Prior treatment with a Mitogen-Activated protein Kinase (MEK) inhibitor or any docetaxel-containing regimen (prior treatment with paclitaxel is acceptable). - Last radiation therapy within 4 weeks prior 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 III, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy and Safety of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Combination With Docetaxel, in Patients Receiving Second Line Treatment for KRAS Mutation-Positive Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB - IV) (SELECT 1)
Principal investigator Pasi Jänne, MD
Description A Phase III, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy and Safety of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Combination with Docetaxel, in Patients receiving second line treatment for KRAS Mutation-Positive Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB - IV) (SELECT-1)
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by AstraZeneca.