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Erlotinib Plus Tivantinib (ARQ 197) Versus Single Agent Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT01395758
Recruitment Status : Completed
First Posted : July 18, 2011
Results First Posted : April 3, 2018
Last Update Posted : April 3, 2018
Sponsor:
Information provided by (Responsible Party):
ArQule

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Metastatic Non-Small Cell Lung Cancer
Interventions: Drug: ARQ 197 plus erlotinib
Drug: Pemetrexed, docetaxel or gemcitabine

  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
No text entered.

Reporting Groups
  Description
Tivantinib Plus Erlotinib Arm Tivantinib 360 mg twice daily (BID) (total daily dose 720 mg) plus erlotinib 150 mg once daily (QD), tablets, orally in 3-week cycles until disease progression or unacceptable toxicity
Chemotherapy Arm Investigator's choice of single agent chemotherapy (pemetrexed, docetaxel, or gemcitabine) administered in 3-week cycles according to the approved label until disease progression or unacceptable toxicity. Subjects who discontinued chemotherapy could be switched to the Crossover Arm (tivantinib plus erlotinib) and continue treatment until disease progression or unacceptable toxicity.
Crossover Arm

Following radiographically confirmed progression, subjects in the Chemotherapy Arm had the option to enroll in the Crossover Arm to receive tivantinib plus erlotinib.

Crossover subjects were treated with tivantinib 360 mg BID (total daily dose 720 mg) plus erlotinib 150 mg QD, tablets, orally in 3-week cycles until disease progression or unacceptable toxicity.


Participant Flow for 2 periods

Period 1:   Open-label Treatment Period
    Tivantinib Plus Erlotinib Arm   Chemotherapy Arm   Crossover Arm
STARTED   51   45   0 
COMPLETED   47   45   0 
NOT COMPLETED   4   0   0 
Withdrawal by Subject                4                0                0 

Period 2:   Crossover Period
    Tivantinib Plus Erlotinib Arm   Chemotherapy Arm   Crossover Arm
STARTED   0   0   26 
COMPLETED   0   0   26 
NOT COMPLETED   0   0   0 



  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
Tivantinib Plus Erlotinib Arm Tivantinib 360 mg BID (total daily dose 720 mg) plus erlotinib 150 mg QD, tablets, orally in 3-week cycles until disease progression or unacceptable toxicity
Chemotherapy Arm Investigator's choice of single agent chemotherapy (pemetrexed, docetaxel, or gemcitabine) administered in 3-week cycles according to the approved label until disease progression or unacceptable toxicity. Subjects who discontinued chemotherapy could be switched to the crossover arm (tivantinib plus erlotinib) and continue treatment until disease progression or unacceptable toxicity.
Total Total of all reporting groups

Baseline Measures
   Tivantinib Plus Erlotinib Arm   Chemotherapy Arm   Total 
Overall Participants Analyzed 
[Units: Participants]
 51   45   96 
Age 
[Units: Participants]
Count of Participants
     
<=18 years      0   0.0%      0   0.0%      0   0.0% 
Between 18 and 65 years      28  54.9%      16  35.6%      44  45.8% 
>=65 years      23  45.1%      29  64.4%      52  54.2% 
Age 
[Units: Years]
Mean (Standard Deviation)
 62.6  (9.23)   65.2  (9.55)   63.8  (9.43) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      33  64.7%      30  66.7%      63  65.6% 
Male      18  35.3%      15  33.3%      33  34.4% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
     
Hispanic or Latino      1   2.0%      0   0.0%      1   1.0% 
Not Hispanic or Latino      50  98.0%      45 100.0%      95  99.0% 
Unknown or Not Reported      0   0.0%      0   0.0%      0   0.0% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
     
American Indian or Alaska Native      0   0.0%      0   0.0%      0   0.0% 
Asian      1   2.0%      2   4.4%      3   3.1% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0% 
Black or African American      1   2.0%      2   4.4%      3   3.1% 
White      47  92.2%      41  91.1%      88  91.7% 
More than one race      0   0.0%      0   0.0%      0   0.0% 
Unknown or Not Reported      2   3.9%      0   0.0%      2   2.1% 
Region of Enrollment 
[Units: Participants]
     
United States   51   45   96 
Cigarette Use 
[Units: Participants]
Count of Participants
     
Yes      46  90.2%      42  93.3%      88  91.7% 
No      5   9.8%      3   6.7%      8   8.3% 
Weight 
[Units: Kilograms]
Mean (Standard Deviation)
 72.50  (17.31)   68.86  (15.19)   70.79  (16.37) 
Height 
[Units: Centimeters]
Mean (Standard Deviation)
 166.38  (10.28)   164.88  (9.42)   165.68  (9.86) 
Eastern Cooperative Oncology Group (ECOG) Performance Status Score [1] 
[Units: Participants]
Count of Participants
     
Grade 0      12  23.5%      8  17.8%      20  20.8% 
Grade 1      32  62.7%      33  73.3%      65  67.7% 
Grade 2      7  13.7%      4   8.9%      11  11.5% 
[1]

Grade 0: Normal activity, fully active. Able to carry on all pre-disease performance without restriction.

Grade 1: 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: In bed < 50% of the time. Ambulatory and capable of all self-care, but unable to carry out work activities. Up and about more than 50% of waking hours.

Confirmation of Kirsten rat sarcoma (KRAS) Mutation 
[Units: Participants]
Count of Participants
     
Yes      51 100.0%      45 100.0%      96 100.0% 
No      0   0.0%      0   0.0%      0   0.0% 


  Outcome Measures

1.  Primary:   Progression-free Survival (PFS) Among Subjects With KRAS Mutation Positive NSCLC (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Single Agent Chemotherapy.   [ Time Frame: Date of randomization until disease progression per RECIST (v 1.1) or death from any cause, whichever came first, assessed up to 24 months. ]

2.  Secondary:   Overall Survival (OS) Among All Eligible Subjects (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Chemotherapy.   [ Time Frame: Date of randomization to the date of death from any cause, assessed up to 24 months ]

3.  Secondary:   Objective Response Rate (ORR) Among All Eligible Subjects (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Chemotherapy.   [ Time Frame: Date of randomization to the date of death from any cause or to the date that the subject discontinues from the study, assessed up to 24 months ]

4.  Secondary:   ORR Among Subjects in the Crossover Period Treated With Erlotinib Plus Tivantinib   [ Time Frame: Date of randomization to the date of death from any cause or to the date that the subject discontinues from the study, assessed up to 24 months. ]


  Serious Adverse Events


  Other Adverse Events


  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

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: Brian Schwartz, MD Chief Medical Officer
Organization: ArQule, Inc.
phone: 781-994-0300
e-mail: ClinicalTrials@arqule.com



Responsible Party: ArQule
ClinicalTrials.gov Identifier: NCT01395758     History of Changes
Other Study ID Numbers: ARQ 197-218
First Submitted: July 1, 2011
First Posted: July 18, 2011
Results First Submitted: January 31, 2018
Results First Posted: April 3, 2018
Last Update Posted: April 3, 2018