Back to resultsImmune-Modulated Study of Selected Small Molecules (Gefitinib, AZD9291, or Selumetinib + Docetaxel) or a 1st Immune-Mediated Therapy (IMT; Tremelimumab) With a Sequential Switch to a 2nd IMT (MEDI4736) in Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer
Primary Purpose
Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (Stage IIIB-IV)
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Gefitinib
AZD9291
Selumetinib+Docetaxel
Tremelimumab
Sponsored by
About this trial
This is an interventional treatment trial for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (Stage IIIB-IV) focused on measuring Lung cancer; NSCLC
Eligibility Criteria
Inclusion Criteria:
- Provision of archived tumor tissue sample and mandatory tissue biopsy
- Patients must have either histologically or cytologically documented NSCLC who present with locally advanced or metastatic stage IIIB-IV disease
- Life expectancy ≥12 weeks
- Patients must have measurable disease and at least 1 lesion not previously irradiated
- World Health Organization (WHO) performance status of 0 or 1
Exclusion Criteria:
- Mixed small cell and NSCLC histology
- Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Gefitinib with a Seq. Switch to a MEDI4736
AZD9291 with a Seq. Switch to a MEDI4736
Selumetinib+Docetaxel with a Seq. Switch to a MEDI4736
Tremelimumab with a Seq. Switch to a MEDI4736
Arm Description
Gefitinib once daily followed by MEDI4736
AZD9291 once daily followed by MEDI4736
Selumetinib twice daily + docetaxel, followed by MEDI4736
Tremelimumab every 4 weeks followed by MEDI4736
Outcomes
Primary Outcome Measures
Confirmed Complete Response (CR) Rate
To assess the efficacy of various sequences. CR (per RECIST 1.1 as assessed by the local/site Investigator) is defined as the disappearance of all target and non-target lesions. Confirmed complete response rate (CR rate) is defined as the number (%) of patients with a confirmed overall response of CR and was based on the evaluable analysis set.
Secondary Outcome Measures
Objective Response Rate (ORR)
To further assess the efficacy of various sequences. Objective response rate (ORR; per RECIST 1.1 as assessed by the site Investigator) is defined as the number (%) of patients with a confirmed overall response of CR or PR and was based on the evaluable analysis set. Per RECIST v1.0 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Progression-free Survival
Progression-free survival (per RECIST 1.1 as assessed by Investigator) is defined as the date of 1st dose of MEDI4736 until the date of objective disease progression or death. Progression of disease (PD) At least a 20% increase in the sum of diameters of TLs, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Duration of Response
Duration of response (DoR; per RECIST 1.1 as assessed by the site Investigator) will be defined as the time from the date of 1st documented response (which is subsequently confirmed) until the 1st date of documented progression or death in the absence of disease progression.
Overall Survival
To assess the efficacy of various sequences. In survival follow up at data cut off.
Full Information
NCT ID
NCT02179671
First Posted
June 30, 2014
Last Updated
August 1, 2019
Sponsor
AstraZeneca
Collaborators
Quintiles, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02179671
Brief Title
Immune-Modulated Study of Selected Small Molecules (Gefitinib, AZD9291, or Selumetinib + Docetaxel) or a 1st Immune-Mediated Therapy (IMT; Tremelimumab) With a Sequential Switch to a 2nd IMT (MEDI4736) in Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer
Official Title
A Phase IIa, Open-Label, Multi-Center, Multi-Cohort, Immune-Modulated Study of Selected Small Molecules (Gefitinib, AZD9291, or Selumetinib + Docetaxel) or a 1st Immune-Mediated Therapy (IMT; Tremelimumab) With a Sequential Switch to a 2nd IMT (MEDI4736) in Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (Stage IIIB-IV)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
July 25, 2014 (Actual)
Primary Completion Date
June 11, 2016 (Actual)
Study Completion Date
June 11, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
Collaborators
Quintiles, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Primary objective: To assess the efficacy of various sequences of either a small molecule or an IMT (IMT-A) followed by a IMT-B (MEDI4736) .
Detailed Description
This is a multi-arm, multi-cohort, Phase IIa, open-label study of selected small molecules (gefitinib, AZD9291, or selumetinib + docetaxel) or 1st IMT (hereafter referred to as IMT-A; tremelimumab) followed by sequential switch to a 2nd IMT (hereafter referred to as IMT-B; MEDI4736) in locally advanced or metastatic NSCLC (Stage IIIB-IV). Patients will be enrolled concurrently into multiple cohorts.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (Stage IIIB-IV)
Keywords
Lung cancer; NSCLC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Gefitinib with a Seq. Switch to a MEDI4736
Arm Type
Experimental
Arm Description
Gefitinib once daily followed by MEDI4736
Arm Title
AZD9291 with a Seq. Switch to a MEDI4736
Arm Type
Experimental
Arm Description
AZD9291 once daily followed by MEDI4736
Arm Title
Selumetinib+Docetaxel with a Seq. Switch to a MEDI4736
Arm Type
Experimental
Arm Description
Selumetinib twice daily + docetaxel, followed by MEDI4736
Arm Title
Tremelimumab with a Seq. Switch to a MEDI4736
Arm Type
Experimental
Arm Description
Tremelimumab every 4 weeks followed by MEDI4736
Intervention Type
Drug
Intervention Name(s)
Gefitinib
Intervention Description
Gefitinib once daily followed by MEDI4736
Intervention Type
Drug
Intervention Name(s)
AZD9291
Intervention Description
AZD9291 once daily followed by MEDI4736
Intervention Type
Drug
Intervention Name(s)
Selumetinib+Docetaxel
Intervention Description
Selumetinib twice daily + docetaxel, followed by MEDI4736
Intervention Type
Drug
Intervention Name(s)
Tremelimumab
Intervention Description
Tremelimumab every 4 weeks followed by MEDI4736
Primary Outcome Measure Information:
Title
Confirmed Complete Response (CR) Rate
Description
To assess the efficacy of various sequences. CR (per RECIST 1.1 as assessed by the local/site Investigator) is defined as the disappearance of all target and non-target lesions. Confirmed complete response rate (CR rate) is defined as the number (%) of patients with a confirmed overall response of CR and was based on the evaluable analysis set.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
To further assess the efficacy of various sequences. Objective response rate (ORR; per RECIST 1.1 as assessed by the site Investigator) is defined as the number (%) of patients with a confirmed overall response of CR or PR and was based on the evaluable analysis set. Per RECIST v1.0 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame
Up to 2 years
Title
Progression-free Survival
Description
Progression-free survival (per RECIST 1.1 as assessed by Investigator) is defined as the date of 1st dose of MEDI4736 until the date of objective disease progression or death. Progression of disease (PD) At least a 20% increase in the sum of diameters of TLs, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame
Up to 2 years
Title
Duration of Response
Description
Duration of response (DoR; per RECIST 1.1 as assessed by the site Investigator) will be defined as the time from the date of 1st documented response (which is subsequently confirmed) until the 1st date of documented progression or death in the absence of disease progression.
Time Frame
Within 12 months
Title
Overall Survival
Description
To assess the efficacy of various sequences. In survival follow up at data cut off.
Time Frame
Up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Provision of archived tumor tissue sample and mandatory tissue biopsy
Patients must have either histologically or cytologically documented NSCLC who present with locally advanced or metastatic stage IIIB-IV disease
Life expectancy ≥12 weeks
Patients must have measurable disease and at least 1 lesion not previously irradiated
World Health Organization (WHO) performance status of 0 or 1
Exclusion Criteria:
Mixed small cell and NSCLC histology
Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Samir N. Khleif, MD
Organizational Affiliation
International Coordinating Investigator
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Goodyear
State/Province
Arizona
ZIP/Postal Code
85338
Country
United States
Facility Name
Research Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Research Site
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Research Site
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
Facility Name
Research Site
City
Ashland
State/Province
Kentucky
ZIP/Postal Code
41101
Country
United States
Facility Name
Research Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Research Site
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
Research Site
City
Huntersville
State/Province
North Carolina
ZIP/Postal Code
28078
Country
United States
Facility Name
Research Site
City
Spokane
State/Province
Washington
ZIP/Postal Code
99208-1129
Country
United States
Facility Name
Research Site
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Immune-Modulated Study of Selected Small Molecules (Gefitinib, AZD9291, or Selumetinib + Docetaxel) or a 1st Immune-Mediated Therapy (IMT; Tremelimumab) With a Sequential Switch to a 2nd IMT (MEDI4736) in Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer
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