Assess Efficacy & Safety of Selumetinib in Combination With Docetaxel in Patients Receiving 2nd Line Treatment for v-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Positive NSCLC

Brief 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

Brief Title

Detailed 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)

Categories

Lung & Chest Cancers

Cancer

Lung

COVID-19

Asthma and Other Respiratory Diseases

Completion Date

2025-12-31

Completion Date Type

Estimated

Conditions

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

Eligibility 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)
* 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

Inclusion 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)
* 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

Gender

All

Gender Based

false

Keywords

Mitogen-Activated Protein Kinase Kinase inhibitor; Non Small Cell Lung Cancer; metastatic; second line treatment for Non Small Cell Lung Cancer; KRAS mutation

Healthy Volunteers

No

Last Update Post Date

Fri, 08/15/2025 - 12:00

Last Update Post Date Type

Actual

Last Update Submit Date

Wed, 08/13/2025 - 12:00

Maximum Age

130 Years

Minimum Age

18 Years

NCT Id

NCT01933932

Org Class

Industry

Org Full Name

AstraZeneca

Org Study Id

D1532C00079

Overall Status

Active, not recruiting

Phases

Phase 3

Primary Completion Date

Tue, 06/07/2016 - 12:00

Primary Completion Date Type

Actual

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)

Primary Outcomes

Outcome Description

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)

Outcome Measure

Progression-Free Survival (PFS)

Outcome 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 Ids

Secondary Id

2013-001676-38

Secondary Outcomes

Outcome Description

Overall Survival is defined as the time from the date of randomisation until death due to any cause.

Outcome Time Frame

Measured at baseline until date of death due to any cause. Estimated final completion : approximately 3.5 years after FSI

Outcome Measure

Overall Survival (OS)

Outcome Description

ORR is defined as the number (%) of subjects with at least one overall visit response of complete response (CR) or partial response (PR). Per RECIST v1.1 for target lesions and assessed by CT/MRI: CR - disappearance of all target lesions; PR - \>=30% decrease in the sum of the longest diameter of target lesion. (Non-target lesion and new lesion results are also taken into account for the overall visit result)

Outcome 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)

Outcome Measure

Objective Response Rate (ORR)

Outcome Description

Duration of response is defined as the time from the date of first documented response until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression)

Outcome 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)

Outcome Measure

Duration of Response (DoR)

Outcome Description

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.

Outcome 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)

Outcome Measure

Symptom Improvement Rate Using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS)

Outcome Description

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.

Outcome 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)

Outcome Measure

Time to Symptom Progression Using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS)