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Erlotinib Hydrochloride and Cabozantinib-s-Malate Alone or in Combination as Second or Third Line Therapy in Treating Patients With Stage IV Non-small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01708954
First received: October 15, 2012
Last updated: October 6, 2016
Last verified: October 2016
Results First Received: October 6, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Non-Small Cell Lung Cancer
Interventions: Drug: Cabozantinib
Drug: Erlotinib

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was activated on February 7, 2013 and closed to accrual on July 1, 2014 with final accrual of 125 patients. Among these, a total of 20 patients registered to Step 2.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Arm A (Erlotinib) Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Arm B (Cabozantinib) Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Arm C (Erlotinib+Cabozantinib) Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Participant Flow for 2 periods

Period 1:   Step 1
    Arm A (Erlotinib)   Arm B (Cabozantinib)   Arm C (Erlotinib+Cabozantinib)
STARTED   42   40   43 
Started Protocol Therapy   40   40   39 
Eligible and Treated   38   38   35 
Patients With MET Status Data Available   30   32   24 
COMPLETED   0 [1]   0 [1]   0 [1] 
NOT COMPLETED   42   40   43 
Disease progression                26                17                14 
Adverse Event                3                11                13 
Death                3                2                3 
Withdrawal by Subject                2                5                3 
Other complicating disease                0                2                0 
Crossed over to Step 2                2                0                0 
Symptomatic deterioration                1                0                1 
Off-treatment reason not submitted                1                1                1 
Ineligible or never received treatment                4                2                8 
[1] Treatment continued until progressive disease or unacceptable toxicity.

Period 2:   Step 2
    Arm A (Erlotinib)   Arm B (Cabozantinib)   Arm C (Erlotinib+Cabozantinib)
STARTED   13 [1]   7 [1]   0 [2] 
COMPLETED   0 [3]   0 [3]   0 
NOT COMPLETED   13   7   0 
Disease progression                9                4                0 
Adverse Event                3                2                0 
Withdrawal by Subject                1                1                0 
[1] Only patients with disease progression in Step 1 are eligible to register to Step 2.
[2] Only patients with disease progression on Arms A and B were allowed to register to Step 2.
[3] Treatment continued until progressive disease or unacceptable toxicity.



  Baseline Characteristics
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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.
Eligible and treated patients

Reporting Groups
  Description
Arm A (Erlotinib) Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Arm B (Cabozantinib) Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Arm C (Erlotinib+Cabozantinib) Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Total Total of all reporting groups

Baseline Measures
   Arm A (Erlotinib)   Arm B (Cabozantinib)   Arm C (Erlotinib+Cabozantinib)   Total 
Overall Participants Analyzed 
[Units: Participants]
 38   38   35   111 
Age 
[Units: Years]
Median (Full Range)
 68 
 (34 to 83) 
 65 
 (46 to 88) 
 63 
 (44 to 82) 
 66 
 (34 to 88) 
Gender 
[Units: Participants]
       
Female   20   24   17   61 
Male   18   14   18   50 


  Outcome Measures
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1.  Primary:   Progression-free Survival (PFS)   [ Time Frame: Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry ]

2.  Secondary:   Overall Survival (OS)   [ Time Frame: Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry ]

3.  Secondary:   Proportion of Patients With Objective Response   [ Time Frame: Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry ]

4.  Secondary:   Proportion of Patients With MET Positivity   [ Time Frame: Assessed at baseline ]

5.  Secondary:   Proportion of Patients With Worst Grade Toxicities of Grade 3 or Higher   [ Time Frame: Assessed every 4 weeks while on treatment and for 30 days after the end of treatment ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Study Statistician
Organization: ECOG-ACRIN Statistical Office
phone: 617-632-3012


Publications of Results:
Neal, J.W., Dahlberg, S.E., Wakelee, H.A., Aisner, J., Bowden, M., Carbone, D.P., Ramalingam, S.S.: A randomized phase 2 trial of cabozantinib, erlotinib or the combination as 2nd or 3rd line therapy in EGFR wild-type NSCLC: ECOG-ACRIN E1512. J Thorac Oncol 2015;10(9)(2):S373. Abstract 30.04.
Neal, J.W., Dahlberg, S.E., Wakelee, H.A., Aisner, S., Bowden, M., Carbone, D.P., Ramalingam, S.S.: Cabozantinib (C), erlotinib (E) or the combination (E+C) as second- or third-line therapy in patients with EGFR wild-type (wt) non-small cell lung cancer (NSCL): A randomized phase 2 trial of the ECOG-ACRIN Cancer Research Group (E1512). J Clin Oncol 2015;33(15s). Abstract 8003.


Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01708954     History of Changes
Other Study ID Numbers: NCI-2012-01938
NCI-2012-01938 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
E1512 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
U10CA180820 ( US NIH Grant/Contract Award Number )
U10CA021115 ( US NIH Grant/Contract Award Number )
Study First Received: October 15, 2012
Results First Received: October 6, 2016
Last Updated: October 6, 2016
Health Authority: United States: Food and Drug Administration