A Phase I/II Clinical Trial of Vorinostat in Combination With Erlotinib for Patients With Relapsed/Refractory Non-Small-Cell Lung Cancer (0683-025)

This study has been terminated.
(This trial is being closed based on lack of substantive efficacy, slow accrual and overall tolerance in patients treated to date.)
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00251589
First received: November 7, 2005
Last updated: February 20, 2014
Last verified: February 2014
Results First Received: October 27, 2008  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Carcinoma, Non-Small-Cell Lung
Interventions: Drug: Vorinostat
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 conducted at 12 investigative sites in the United States. The first patient’s first visit was 30 March 2006. The study was terminated early on 12 Oct 2007 and the last patient’s last visit was 30 Oct 2007.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Enrolled patients were assigned to 1 of 2 dose escalating cohorts (A and B) in the Phase I portion of the study to determine the maximum tolerated dose (MTD). Once determined, new patients were assigned to the Phase II portion of the study and treated with the MTD. Active Phase I patients continued into Phase II.

Reporting Groups
  Description
Vorinostat 200 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk Vorinostat 200 mg twice a day for 3 days a week + erlotinib 150 mg once a day was evaluated in the Phase I portion of the study and determined to be the MTD and therefore the recommended Phase II dose. Of the 16 patients treated at this dose level, 4 were assigned to the Phase I portion of the study and 12 were assigned to the Phase II portion.
Vorinostat 300 mg q.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk Vorinostat 300 mg once a day for 3 days a week + erlotinib 150 mg once a day was evaluated in the Phase I portion of the amended study and exceeded the MTD. All patients treated at this dose level were assigned to the Phase I portion of the study.
Vorinostat 300 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk Vorinostat 300 mg twice a day for 3 days a week + erlotinib 150 mg once a day was evaluated in the Phase I portion of the study and exceeded the MTD. All patients treated at this dose level were assigned to the Phase I portion of the study.
Vorinostat 400 mg q.d. 21d/4wk + Erlotinib 150 mg q.d. 7d/wk Vorinostat 400 mg once a day for 21 out of 28 days + erlotinib 150 mg once a day was evaluated in the Phase I portion of the original study and exceeded MTD. This cohort was then amended (Amendment 1) to identify a more tolerable once daily vorinostat dosing regimen. All patients treated at this dose level were assigned to the Phase I portion of the study.

Participant Flow:   Overall Study
    Vorinostat 200 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk     Vorinostat 300 mg q.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk     Vorinostat 300 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk     Vorinostat 400 mg q.d. 21d/4wk + Erlotinib 150 mg q.d. 7d/wk  
STARTED     16 [1]   3     2     2  
COMPLETED     1     0     0     0  
NOT COMPLETED     15     3     2     2  
Adverse Event                 5                 1                 2                 1  
Withdrawal by Subject                 1                 1                 0                 0  
Discontinued due to progressive disease                 9                 1                 0                 1  
[1] 4 of the 16 patients participated in Phase I and II portions. 12 participated in Phase II only.



  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.
No text entered.

Reporting Groups
  Description
Vorinostat 200 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk Vorinostat 200 mg twice a day for 3 days a week + erlotinib 150 mg once a day was evaluated in the Phase I portion of the study and determined to be the MTD and therefore the recommended Phase II dose. Of the 16 patients treated at this dose level, 4 were assigned to the Phase I portion of the study and 12 were assigned to the Phase II portion.
Vorinostat 300 mg q.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk Vorinostat 300 mg once a day for 3 days a week + erlotinib 150 mg once a day was evaluated in the Phase I portion of the amended study and exceeded the MTD. All patients treated at this dose level were assigned to the Phase I portion of the study.
Vorinostat 300 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk Vorinostat 300 mg twice a day for 3 days a week + erlotinib 150 mg once a day was evaluated in the Phase I portion of the study and exceeded the MTD. All patients treated at this dose level were assigned to the Phase I portion of the study.
Vorinostat 400 mg q.d. 21d/4wk + Erlotinib 150 mg q.d. 7d/wk Vorinostat 400 mg once a day for 21 out of 28 days + erlotinib 150 mg once a day was evaluated in the Phase I portion of the original study and exceeded MTD. This cohort was then amended (Amendment 1) to identify a more tolerable once daily vorinostat dosing regimen. All patients treated at this dose level were assigned to the Phase I portion of the study.
Total Total of all reporting groups

Baseline Measures
    Vorinostat 200 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk     Vorinostat 300 mg q.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk     Vorinostat 300 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk     Vorinostat 400 mg q.d. 21d/4wk + Erlotinib 150 mg q.d. 7d/wk     Total  
Number of Participants  
[units: participants]
  16     3     2     2     23  
Age  
[units: Years]
Mean ± Standard Deviation
  53.0  ± 4.36     66.0  ± 8.49     48.5  ± 20.51     59.1  ± 11.59     60.7  ± 11.41  
Age, Customized  
[units: Participants]
         
≤ 65 years     11     3     1     2     17  
> 65 years     5     0     1     0     6  
Gender  
[units: participants]
         
Female     8     2     1     1     12  
Male     8     1     1     1     11  



  Outcome Measures
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1.  Primary:   Dose Limiting Toxicity (DLT) Occurring in Cycle 1 of the Phase I Portion of the Study   [ Time Frame: Day 1 to 28 in the Phase I portion of the study ]

2.  Primary:   Dose Limiting Toxicity Occurring in Cycle 1 of the Phase II Portion of the Study   [ Time Frame: Day 1 to 28 in the Phase II portion of the study ]

3.  Secondary:   Unconfirmed Partial Response (UPR) Based on Response Criteria in Solid Tumors (RECIST)   [ Time Frame: Every 57 days beginning with Cycle 3, or more frequently if appropriate ]

4.  Secondary:   Stable Disease (SD) as Best Response Based on Response Criteria in Solid Tumors (RECIST)   [ Time Frame: Every 57 days beginning with Cycle 3, or more frequently if appropriate ]

5.  Secondary:   Progressive Disease (PD) as Best Response Based on Response Criteria in Solid Tumors (RECIST)   [ Time Frame: Every 57 days beginning with Cycle 3, or more frequently if appropriate ]

6.  Secondary:   Disease Progression After Week 8 Based on Response Criteria in Solid Tumors (RECIST)   [ Time Frame: Every 57 days beginning with Cycle 3 (Week 8), or more frequently if appropriate ]

7.  Secondary:   Progression-free Survival   [ Time Frame: Day 1 to disease progression or death ]

8.  Post-Hoc:   Dose Limiting Toxicity Occurring in Cycles 2 and Beyond of the Phase II Portion of the Study   [ Time Frame: After day 28 in the Phase II portion of the study ]


  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
Due to the slow pace of patient accrual, failure to observe meaningful efficacy in treated patients, and overall intolerance of the combination regimen, the study was terminated prematurely on 12-Oct-2007.


  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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
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.


Results Point of Contact:  
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372
e-mail: ClinicalTrialsDisclosure@merck.com


No publications provided


Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00251589     History of Changes
Other Study ID Numbers: 0683-025, MK0683-025, 2005_080
Study First Received: November 7, 2005
Results First Received: October 27, 2008
Last Updated: February 20, 2014
Health Authority: United States: Food and Drug Administration