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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02179671
Recruitment Status : Completed
First Posted : July 2, 2014
Results First Posted : August 2, 2019
Last Update Posted : August 2, 2019
Sponsor:
Collaborator:
Quintiles, Inc.
Information provided by (Responsible Party):
AstraZeneca

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) .

Condition or disease Intervention/treatment Phase
Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (Stage IIIB-IV) Drug: Gefitinib Drug: AZD9291 Drug: Selumetinib+Docetaxel Drug: Tremelimumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : July 25, 2014
Actual Primary Completion Date : June 11, 2016
Actual Study Completion Date : June 11, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Gefitinib with a Seq. Switch to a MEDI4736
Gefitinib once daily followed by MEDI4736
Drug: Gefitinib
Gefitinib once daily followed by MEDI4736

Experimental: AZD9291 with a Seq. Switch to a MEDI4736
AZD9291 once daily followed by MEDI4736
Drug: AZD9291
AZD9291 once daily followed by MEDI4736

Experimental: Selumetinib+Docetaxel with a Seq. Switch to a MEDI4736
Selumetinib twice daily + docetaxel, followed by MEDI4736
Drug: Selumetinib+Docetaxel
Selumetinib twice daily + docetaxel, followed by MEDI4736

Experimental: Tremelimumab with a Seq. Switch to a MEDI4736
Tremelimumab every 4 weeks followed by MEDI4736
Drug: Tremelimumab
Tremelimumab every 4 weeks followed by MEDI4736




Primary Outcome Measures :
  1. Confirmed Complete Response (CR) Rate [ Time Frame: Up to 2 years ]
    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 :
  1. Objective Response Rate (ORR) [ Time Frame: Up to 2 years ]
    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.

  2. Progression-free Survival [ Time Frame: Up to 2 years ]
    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.

  3. Duration of Response [ Time Frame: Within 12 months ]
    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.

  4. Overall Survival [ Time Frame: Up to 2 years ]
    To assess the efficacy of various sequences. In survival follow up at data cut off.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02179671


Locations
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United States, Arizona
Research Site
Goodyear, Arizona, United States, 85338
United States, District of Columbia
Research Site
Washington, District of Columbia, United States, 20007
United States, Georgia
Research Site
Augusta, Georgia, United States, 30912
Research Site
Marietta, Georgia, United States, 30060
United States, Kentucky
Research Site
Ashland, Kentucky, United States, 41101
United States, Missouri
Research Site
Saint Louis, Missouri, United States, 63110
United States, New York
Research Site
Mineola, New York, United States, 11501
United States, North Carolina
Research Site
Huntersville, North Carolina, United States, 28078
United States, Washington
Research Site
Spokane, Washington, United States, 99208-1129
Research Site
Tacoma, Washington, United States, 98405
Sponsors and Collaborators
AstraZeneca
Quintiles, Inc.
Investigators
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Principal Investigator: Samir N. Khleif, MD International Coordinating Investigator

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02179671    
Other Study ID Numbers: D4191C00011
First Posted: July 2, 2014    Key Record Dates
Results First Posted: August 2, 2019
Last Update Posted: August 2, 2019
Last Verified: August 2019
Keywords provided by AstraZeneca:
Lung cancer; NSCLC
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Docetaxel
Gefitinib
Durvalumab
Tremelimumab
Osimertinib
Antibodies, Monoclonal
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Immunological
Immunologic Factors
Physiological Effects of Drugs