This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Randomized Phase II Study of AZD6244 (Mitogen-activated Protein Kinase Inhibitor) MEK-Inhibitor With Erlotinib in KRAS Wild Type Advanced Non-Small Cell Lung Cancer (NSCLC) and a Randomized Phase II Study of AZD6244 With Erlotinib in Mutant KRAS Adva...

This study has been completed.
Sponsor:
Collaborators:
University of California, Davis
University of Chicago
University of Southern California
City of Hope Medical Center
Information provided by (Responsible Party):
Arun Rajan, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01229150
First received: October 26, 2010
Last updated: April 17, 2017
Last verified: April 2017
Results First Received: October 23, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: No masking;   Primary Purpose: Treatment
Condition: Non Small Cell Lung Carcinoma
Interventions: Drug: AZD6244
Drug: Erlotinib
Drug: AZD6244 + Erlotinib

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
89 participants were enrolled and 79 participants started. 10 patients should be classified as screen failures. Of the 10, one died during the screening process, and one patient withdrew during the screening process.

Reporting Groups
  Description
KRAS Mut 2

KRAS Mutant patients randomized to combination therapy arm

AZD6244 + Erlotinib: For KRAS mutant patients and Wild-Type KRAS patients randomized to the combination arm (arms are stratified based on KRAS mutational status), AZD6244 150 mg qd (every day) + erlotinib mg qd.

KRAS Mut 1

KRAS Mutant patients randomized to monotherapy arm

AZD6244: For KRAS mutant patients randomized to the single agent arm, AZD6244 75 mg bid (twice a day).

WT KRAS 1

Wild-Type KRAS patients randomized to monotherapy arm

Erlotinib: For Wild-Type KRAS patients randomized to the single agent arm, Erlotinib 150 mg qd

WT KRAS 2

Wild-Type KRAS patients randomized to combination therapy arm

AZD6244 + Erlotinib: For KRAS mutant patients and Wild-Type KRAS patients randomized to the combination arm (arms are stratified based on KRAS mutational status), AZD6244 150 mg qd + erl mg qd.


Participant Flow:   Overall Study
    KRAS Mut 2   KRAS Mut 1   WT KRAS 1   WT KRAS 2
STARTED   30   11   19   19 
COMPLETED   28   9   19   19 
NOT COMPLETED   2   2   0   0 
Toxicity                2                2                0                0 



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
KRAS Mut 2

KRAS Mutant patients randomized to combination therapy arm

AZD6244 + Erlotinib: For KRAS mutant patients and Wild-Type KRAS patients randomized to the combination arm (arms are stratified based on KRAS mutational status), AZD6244 150 mg qd (every day) + erlotinib mg qd.

KRAS Mut 1

KRAS Mutant patients randomized to monotherapy arm

AZD6244: For KRAS mutant patients randomized to the single agent arm, AZD6244 75 mg bid (twice a day).

WT KRAS 1

Wild-Type KRAS patients randomized to monotherapy arm

Erlotinib: For Wild-Type KRAS patients randomized to the single agent arm, Erlotinib 150 mg qd

WT KRAS 2

Wild-Type KRAS patients randomized to combination therapy arm

AZD6244 + Erlotinib: For KRAS mutant patients and Wild-Type KRAS patients randomized to the combination arm (arms are stratified based on KRAS mutational status), AZD6244 150 mg qd + erl mg qd.

Total Total of all reporting groups

Baseline Measures
   KRAS Mut 2   KRAS Mut 1   WT KRAS 1   WT KRAS 2   Total 
Overall Participants Analyzed 
[Units: Participants]
 30   11   19   19   79 
Age 
[Units: Participants]
Count of Participants
         
<=18 years      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Between 18 and 65 years      16  53.3%      5  45.5%      11  57.9%      10  52.6%      42  53.2% 
>=65 years      14  46.7%      6  54.5%      8  42.1%      9  47.4%      37  46.8% 
Age 
[Units: Years]
Mean (Standard Deviation)
 66.05  (9.648)   64.31  (13.76)   63.75  (13.6)   64.84  (8.10)   65.22  (9.46) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
         
Female      16  53.3%      7  63.6%      9  47.4%      6  31.6%      38  48.1% 
Male      14  46.7%      4  36.4%      10  52.6%      13  68.4%      41  51.9% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
         
Hispanic or Latino      1   3.3%      2  18.2%      2  10.5%      3  15.8%      8  10.1% 
Not Hispanic or Latino      25  83.3%      9  81.8%      15  78.9%      12  63.2%      61  77.2% 
Unknown or Not Reported      4  13.3%      0   0.0%      2  10.5%      4  21.1%      10  12.7% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
         
American Indian or Alaska Native      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Asian      1   3.3%      1   9.1%      0   0.0%      1   5.3%      3   3.8% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Black or African American      3  10.0%      2  18.2%      4  21.1%      4  21.1%      13  16.5% 
White      26  86.7%      8  72.7%      14  73.7%      13  68.4%      61  77.2% 
More than one race      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Unknown or Not Reported      0   0.0%      0   0.0%      1   5.3%      1   5.3%      2   2.5% 
Region of Enrollment 
[Units: Participants]
Count of Participants
         
United States   30   11   19   19   79 
Histology 
[Units: Participants]
Count of Participants
         
Lung Cancer Adenocarcinoma   30   11   15   15   71 
Squamous cell   0   0   4   4   8 
Mutational Status [1] 
[Units: Participants]
Count of Participants
         
EGFR Mutated (L858R)   30   11   1   1   43 
EGFR Wild Type   0   0   18   18   36 
KRAS G12A   6   0   0   0   6 
KRAS G12C   8   4   0   0   12 
KRAS G12D   1   1   0   0   2 
KRAS G12K   1   1   0   0   2 
KRAS G12R   0   1   0   0   1 
KRAS G12S   1   0   0   0   1 
KRAS G12V   9   4   0   0   13 
KRAS Q61H   2   0   0   0   2 
KRAS Q61L   2   0   0   0   2 
KRAS   0   0   0   0   0 
[1] EGFR (epidermal growth factor receptor); KRAS (Kirsten Rat Sarcoma Viral Oncogene homolog). KRAS G12A (e.g. G is glycine, 12 is the codon or position and A is amino acid alanine); C is cysteine, D is aspartic acid, K is lysine, R is arginine, S is serine, V is valine, Q is glutamine, H is histidine, and L is leucine.
Eastern Cooperative Oncology Group (ECOG) [1] 
[Units: Participants]
Count of Participants
         
 3   1   2   2   8 
 14   5   11   7   37 
 13   5   6   10   34 
[1] ECOG Performance Status criteria: Grade 0 is normal activity. Fully active, able to carry on all pre-disease performance without restriction. Grade 1 is symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work). Grade 2 is in bed <50% of the time. Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours.
No. of Prior Regimens 
[Units: Participants]
Count of Participants
         
 12   6   10   8   36 
 18   5   9   11   43 
Smoking 
[Units: Participants]
Count of Participants
         
Current   9   0   0   0   9 
Former   21   11   13   16   61 
Never-smoker   0   0   6   3   9 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Progression Free Survival   [ Time Frame: 2.1 to 4 months ]

2.  Primary:   Objective Response   [ Time Frame: Up to 37 months ]

3.  Secondary:   Number of Participants With Adverse Events   [ Time Frame: 42 months ]

4.  Secondary:   Percentage of Participants With Disease Control/Stabilization   [ Time Frame: 3 cycles or up to 84 days ]

5.  Secondary:   Overall Survival   [ Time Frame: Up to 26 months ]

6.  Secondary:   Percentage of Th17 in Cluster of Differentiation 4 (CD4)+T Cells at Baseline in Relation to Response   [ Time Frame: Pretreatment - Cycle 1 Day 1 ]

7.  Secondary:   Number of Participants With a Reduction in Phosphorylated Extracellular Signal-Regulated Kinases (p-ERK) in Lymphocytes   [ Time Frame: Cycle 1 Day 1 pre-treatment with Cycle 1 Day 2 (1 day after starting treatment), and Cycle 1 Day 14 (2 weeks after starting treatment) ]

8.  Other Pre-specified:   Number of Participants With Changes in a Tumor's MIB-1 (Ki-67) Rate   [ Time Frame: At enrollment ]

9.  Other Pre-specified:   Change in T Cell Immunoglobulin Mucin 3 (TIM-3) on Tregs   [ Time Frame: Cycle 1 Day 1 pre-treatment with Cycle 1 Day 2 (1 day after starting treatment), and Cycle 1 Day 14 (2 weeks after starting treatment) ]

10.  Other Pre-specified:   Change in Cytotoxic T-lymphocyte Associated Protein 4 (CTLA-4) Expression on Tregs   [ Time Frame: Cycle 1 Day 1 pre-treatment with Cycle 1 Day 2 (1 day after starting treatment), and Cycle 1 Day 14 (2 weeks after starting treatment) ]

11.  Other Pre-specified:   Change in Programmed Cell Death-1 (PD-1) Expression on Tregs   [ Time Frame: Cycle 1 Day 1 pre-treatment with Cycle 1 Day 2 (1 day after starting treatment), and Cycle 1 Day 14 (2 weeks after starting treatment) ]

12.  Other Pre-specified:   Change in Programmed Cell Death-1 (PD-1) Expression on Cluster of Differentiation 8 (CD8)+T Cells   [ Time Frame: Cycle 1 Day 1 pre-treatment with Cycle 1 Day 2 (1 day after starting treatment), and Cycle 1 Day 14 (2 weeks after starting treatment) ]

13.  Other Pre-specified:   Phospho-ERK (p-ERK), Phospho Protein Kinase B (p-AKt) and Phosphatase and Tensin Homolog (PTEN) Expression Testing   [ Time Frame: At enrollment ]

14.  Other Pre-specified:   Number of Participants With Overexpression of Estimated Glomerular Filtration Rate (EGFR) and c-MET   [ Time Frame: At enrollment ]

15.  Other Pre-specified:   Number of Participants Who Underwent Mutational Analysis for Estimated Glomerular Filtration Rate (EGFR), Mitogen-activated Protein Kinase 1 (MEK 1), Proto-oncogene B-Raf (BRAF), and LKB1   [ Time Frame: At enrollment ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Arun Rajan
Organization: National Cancer Institute
phone: 301-594-5322
e-mail: rajana@mail.nih.gov


Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Arun Rajan, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT01229150     History of Changes
Obsolete Identifiers: NCT01239290
Other Study ID Numbers: 100218
10-C-0218
Study First Received: October 26, 2010
Results First Received: October 23, 2014
Last Updated: April 17, 2017