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 (SELECT-1)

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ClinicalTrials.gov Identifier: NCT01933932

Recruitment Status : Active, not recruiting

First Posted : September 2, 2013

Results First Posted : August 29, 2017

Last Update Posted : October 17, 2023

View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

AstraZeneca

Tracking Information

First Submitted Date ^ICMJE

August 29, 2013

First Posted Date ^ICMJE

September 2, 2013

Results First Submitted Date ^ICMJE

February 27, 2017

Results First Posted Date ^ICMJE

August 29, 2017

Last Update Posted Date

October 17, 2023

Actual Study Start Date ^ICMJE

September 25, 2013

Actual Primary Completion Date

June 7, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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) ]

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)

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Current Secondary Outcome Measures ^ICMJE

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 ]
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. Estimated final completion : approximately 3 years after first subject in (FSI) ]
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)
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) ]
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)
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) ]
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 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 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.

Original Secondary Outcome Measures ^ICMJE

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 ]
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.Estimated final completion : approximately 3 years after first subject in (FSI) ]
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 (DoR) [ Time Frame: Measured from date of randomisation until 30 days post treatment discontinuation. Estimated final completion : approximately 3 years after first subject in (FSI) ]
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
Symptom improvement rate (using ASBI from LCSS) [ Time Frame: Measured from date of randomisation until 30 days post treatment discontinuation. Estimated final completion : approximately 3 years after first subject in (FSI) ]
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. Estimated final completion : approximately 3 years after first subject in (FSI) ]
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.
Investigate safety and tolerability profie 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) ]
Aderse events graded according to the National Cancer Insitute Common Terminology Criteria for AEs (CTCAE)
Investigate safety and tolerability profie 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) ]
Laboratory parameter: Clinical chemistry, haematology and urinalysis
Investigate safety and tolerability profie 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) ]
Vital signs assessments inlcude weight, body temperature and supine blood pressure.
Investigate safety and tolerability profie of Selumetinib in combination with docetaxel compared with placebo in combination with docetaxel by assessing ECHO/MUGA [ 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) ]
Echocardiogram will be performed before the start of selumetinib therapy, every 12 weeks and as clinically indicated during the course of the study until 30 days after the last dose of selumetinib. If an echocardiogram scan cannot be taken, a MUGA scan will be conducted.
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) ]

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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)

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

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)

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition ^ICMJE

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

Intervention ^ICMJE

Drug: Selumetinib
Three 25 mg selumetinib capsules (Hyd-Sulfate) be administered orally, twice daily, (total dose 75 mg dose bd) on an uninterrupted schedule.

Other Name: AZD6244; ARRY-142886
Drug: Docetaxel
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 in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.
Drug: Pegylated G-CSF
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.

Other Name: Pegfilgrastim 6 mg

Study Arms ^ICMJE

Experimental: Selumetinib + Docetaxel
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
Interventions:
- Drug: Selumetinib
- Drug: Docetaxel
- Drug: Pegylated G-CSF
Experimental: Placebo + Docetaxel
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.
Interventions:
- Drug: Docetaxel
- Drug: Placebo
- Drug: Pegylated G-CSF

Publications *

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Active, not recruiting

Actual Enrollment ^ICMJE

510

Original Estimated Enrollment ^ICMJE

634

Estimated Study Completion Date ^ICMJE

December 29, 2023

Actual Primary Completion Date

June 7, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years to 130 Years (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, France, Germany, Hungary, Israel, Italy, Mexico, Netherlands, Peru, Poland, Portugal, Romania, Russian Federation, Spain, Sweden, Turkey, Ukraine, United Kingdom, United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT01933932

Other Study ID Numbers ^ICMJE

D1532C00079
2013-001676-38 ( EudraCT Number )

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Not Provided

IPD Sharing Statement ^ICMJE

Plan to Share IPD:	Yes
Plan Description:	Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Supporting Materials:	Study Protocol
Supporting Materials:	Statistical Analysis Plan (SAP)
Time Frame:	AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Access Criteria:	When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
URL:	https://astrazenecagroup-dt.pharmacm.com/DT/Home