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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 : March 28, 2019
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 March 28, 2019
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
 (submitted: August 29, 2013)
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 Complete list of historical versions of study NCT01933932 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 28, 2017)
  • 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
 (submitted: August 29, 2013)
  • 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
 (submitted: August 28, 2017)
510
Original Estimated Enrollment  ICMJE
 (submitted: August 29, 2013)
634
Estimated Study Completion Date  ICMJE December 31, 2019
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 No
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 Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Gabriella Mariani, MD AstraZeneca UK, MSD
Principal Investigator: Pasi Jänne, MD Dana-Faber Cancer Institute, USA
PRS Account AstraZeneca
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP