Back to resultsAssess Safety & Efficacy of Selumetinib When Given in Combination With Standard First Line Treatment for Advanced Non-small Cell Lung Cancer (SELECT-3)
Primary Purpose
Locally Advanced or Metastatic NSCL Cancer Stage IIIB IV
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
selumetinib
gemcitabine
cisplatin
carboplatin
pemetrexed
Sponsored by
About this trial
This is an interventional treatment trial for Locally Advanced or Metastatic NSCL Cancer Stage IIIB IV focused on measuring MEK1/2 inhibitor,, Non Small Cell Lung Cancer,, metastatic,, first line treatment for Non Small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
- Provision of signed, written and dated 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)
- Female patients must not be breast-feeding and have a negative pregnancy test prior to start of dosing or must have evidence of non-child-bearing potential
- Patients must be eligible to receive treatment with the platinum doublet combination with which selumetinib is being combined and in accordance with the local product information
Exclusion Criteria:
- Prior chemotherapy or other systemic anti-cancer treatment for advanced NSCLC.
- Prior surgery or radiotherapy within 6 months or palliative radiotherapy within 4 weeks of start of study treatment.
- Female patients who are breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
- Another primary malignancy within 5 years of starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ.
- As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, active bleeding diatheses, renal transplant, or active infection
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Selumetinib+standard chemotherapy
Arm Description
Selumetinib plus gemcitabine; or pemetrexed and cisplatin or carboplatin
Outcomes
Primary Outcome Measures
Dose Limiting Toxicity (DLT) Events in Chemotherapy in Combination With Selumetinib
Any toxicity not attributable to the disease or disease-related processess under investigation, considered related to the combination of chemotherapy plus selumetinib, which occurs within the timeframe and is dose limiting
Secondary Outcome Measures
Best Objective Response
The best response a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression. Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); Progressive Disease (PD), >=20% increase in the sum of the longest diameter of target lesions, the sum must also demonstrate an absolute increase of >=5mm; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm
Percentage Change From Baseline at 6 Weeks in Target Lesion Size
The percentage change in the sum of the diameters of target lesions
Best Percentage Change From Baseline in Target Lesion Size
The best percentage change in tumour size a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression. Percentage change was derived at each visit by the percentage change in the sum of the diameters of target lesions
Objective Response Rate (ORR)
The number of patients who had at least 1 confirmed visit response of Complete Response (CR) or Partial Response (PR) prior to any evidence of progression. Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm; Objective Response Rate (ORR) = CR + PR
AUC (0-tau)
Area under the concentration time curve (AUC) over a dosing interval at steady state (0-tau)
Cmax,ss
Maximum plasma concentration at steady state
Tmax,ss
Time to reach maximum plasma concentration at steady state
CL/F
Apparent oral plasma clearance
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01809210
Brief Title
Assess Safety & Efficacy of Selumetinib When Given in Combination With Standard First Line Treatment for Advanced Non-small Cell Lung Cancer
Acronym
SELECT-3
Official Title
A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Selumetinib (AZD6244; ARRY-142886) in Combination With First Line Chemotherapy Regimens in Patients With Non-Small Cell Lung Cancer (NSCLC)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
April 4, 2013 (Actual)
Primary Completion Date
January 4, 2016 (Actual)
Study Completion Date
January 4, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Phase I, open label multicentre study of selumetinib administered orally in combination with first line chemotherapy regimens to patients with advanced/metastatic NSCLC. The study has been designed to allow an investigation of the optimal dose of selumetinib in combination with various standard first line double-platinum chemotherapy regimens. Initial assessment will be based on tolerability of selumetinib in combination with one or more selected regimens that are considered to be tolerated also being assessed for preliminary evidence of activity.
This study is a dose finding and optional cohort expansion; In addition all patients will be assessed for anti-cancer efficacy of the combination of selumetinib and chemotherapy.
Detailed Description
A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Selumetinib (AZD6244; ARRY-142886) in Combination with First Line Chemotherapy Regimens in Patients with Non-Small Cell Lung Cancer (NSCLC)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced or Metastatic NSCL Cancer Stage IIIB IV
Keywords
MEK1/2 inhibitor,, Non Small Cell Lung Cancer,, metastatic,, first line treatment for Non Small Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
55 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Selumetinib+standard chemotherapy
Arm Type
Experimental
Arm Description
Selumetinib plus gemcitabine; or pemetrexed and cisplatin or carboplatin
Intervention Type
Drug
Intervention Name(s)
selumetinib
Intervention Description
2 x 25mg capsules bd continuously in cohort 1 (with gemcitabine and cisplatin). If tolerated - next cohort 3 x 25mg capsules bd continuously. if higher doses are explored, required number of capsules will be provided. Option to administer on D2-19 of each 21 day cycle if required to assess tolerability of combinations with chemotherapy
Intervention Type
Drug
Intervention Name(s)
gemcitabine
Intervention Description
1250 mg/m2 iv on Day 1 and 8 of each 21 day cycle. If combination not tolerated, option to give 1000 mg/m2 iv on Day 1 and Day 8 of each 21 day cycle
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Description
75 mg/m2 iv on Day 1 of each 21 day cycle. If combination not tolerated, option to give 50 mg/m2 iv on Day 1 or 25mg/m2 iv on Day 1 and Day 8 of each 21 day cycle
Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Description
If it is not possible to identify a tolerable combination of selumetinib, gemcitabine and cisplatin, cisplatin may be replaced with carboplatin (AUC5) iv on Day 1 of each 21 day cycle
Intervention Type
Drug
Intervention Name(s)
pemetrexed
Intervention Description
Gemcitabine may be replaced with pemetrexed 500 mg/m2 iv on Day 1 of each 21 day cycle.
Primary Outcome Measure Information:
Title
Dose Limiting Toxicity (DLT) Events in Chemotherapy in Combination With Selumetinib
Description
Any toxicity not attributable to the disease or disease-related processess under investigation, considered related to the combination of chemotherapy plus selumetinib, which occurs within the timeframe and is dose limiting
Time Frame
The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks
Secondary Outcome Measure Information:
Title
Best Objective Response
Description
The best response a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression. Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); Progressive Disease (PD), >=20% increase in the sum of the longest diameter of target lesions, the sum must also demonstrate an absolute increase of >=5mm; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm
Time Frame
Screening, week 6 and week 12
Title
Percentage Change From Baseline at 6 Weeks in Target Lesion Size
Description
The percentage change in the sum of the diameters of target lesions
Time Frame
Week 6
Title
Best Percentage Change From Baseline in Target Lesion Size
Description
The best percentage change in tumour size a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression. Percentage change was derived at each visit by the percentage change in the sum of the diameters of target lesions
Time Frame
Screening, week 6 and week 12
Title
Objective Response Rate (ORR)
Description
The number of patients who had at least 1 confirmed visit response of Complete Response (CR) or Partial Response (PR) prior to any evidence of progression. Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm; Objective Response Rate (ORR) = CR + PR
Time Frame
Up until progression or last evaluable assessment in the absence of progression, up to 9 months
Title
AUC (0-tau)
Description
Area under the concentration time curve (AUC) over a dosing interval at steady state (0-tau)
Time Frame
Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
Title
Cmax,ss
Description
Maximum plasma concentration at steady state
Time Frame
Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
Title
Tmax,ss
Description
Time to reach maximum plasma concentration at steady state
Time Frame
Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
Title
CL/F
Description
Apparent oral plasma clearance
Time Frame
Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Provision of signed, written and dated 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)
Female patients must not be breast-feeding and have a negative pregnancy test prior to start of dosing or must have evidence of non-child-bearing potential
Patients must be eligible to receive treatment with the platinum doublet combination with which selumetinib is being combined and in accordance with the local product information
Exclusion Criteria:
Prior chemotherapy or other systemic anti-cancer treatment for advanced NSCLC.
Prior surgery or radiotherapy within 6 months or palliative radiotherapy within 4 weeks of start of study treatment.
Female patients who are breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
Another primary malignancy within 5 years of starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ.
As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, active bleeding diatheses, renal transplant, or active infection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gabriella Mariani, MD
Organizational Affiliation
AstraZeneca UK, MSD
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Emma Dean, BMEDSCI, BM, BS, PHD
Organizational Affiliation
The Christie NHS Foundation Trust, UK
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Fiona Blackhall, PhD, FRCP
Organizational Affiliation
The Christie NHS Foundation Trust Clinical Trials Unit; UK
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Glasgow
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Facility Name
Research Site
City
London
ZIP/Postal Code
W1G 6AD
Country
United Kingdom
Facility Name
Research Site
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Research Site
City
Newcastle upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
12. IPD Sharing Statement
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=1179&filename=D1532C00070revisedCSP-2_Redacted.pdf
Description
D1532C00070revisedCSP-2_Redacted
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Assess Safety & Efficacy of Selumetinib When Given in Combination With Standard First Line Treatment for Advanced Non-small Cell Lung Cancer
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