A Pharmacokinetic/Pharmacodynamic Study of RO5185426 in Previously Treated Patients With Metastatic Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01107418
First received: April 12, 2010
Last updated: July 29, 2015
Last verified: July 2015
Results First Received: July 29, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Pharmacokinetics/Dynamics Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Malignant Melanoma
Intervention: Drug: RO5185426

  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
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
Vemurafenib – All Cohorts Participants received vemurafenib (RO5185426) film-coated tablets, orally, twice daily at doses of 240, 480, 720, or 960 milligrams (mg) on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.

Participant Flow:   Overall Study
    Vemurafenib – All Cohorts  
STARTED     52  
COMPLETED     0  
NOT COMPLETED     52  
Disease Progression                 45  
Adverse Event                 3  
Withdrawal by Subject                 1  
Study Closing                 1  
Started Other Therapy                 1  
Entered Extension Study                 1  



  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.
Safety population included all participants who received at least one dose of vemurafenib.

Reporting Groups
  Description
Cohort 1 - Vemurafenib 240 mg Participants received vemurafenib film-coated tablet, orally, twice daily at a dose of 240 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
Cohort 2 - Vemurafenib 480 mg Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 480 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
Cohort 3 - Vemurafenib 720 mg Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 720 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants received vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
Cohort 4 - Vemurafenib 960 mg Participants received vemurafenib film-coated tablets, orally, twice daily at a dose of 960 mg on Days 1 to 15 (a single morning dose was administered on Day 15). Starting at Day 22, participants resumed vemurafenib 960 mg film-coated tablets orally twice daily in 21-day cycles until the development of progressive disease, unacceptable toxicity, consent withdrawal, or any other criteria for removal.
Total Total of all reporting groups

Baseline Measures
    Cohort 1 - Vemurafenib 240 mg     Cohort 2 - Vemurafenib 480 mg     Cohort 3 - Vemurafenib 720 mg     Cohort 4 - Vemurafenib 960 mg     Total  
Number of Participants  
[units: participants]
  12     12     12     16     52  
Age  
[units: years]
Mean (Standard Deviation)
  52.0  (15.06)     46.3  (10.58)     54.3  (10.70)     50.5  (11.91)     50.8  (12.14)  
Gender  
[units: participants]
         
Female     5     7     6     8     26  
Male     7     5     6     8     26  



  Outcome Measures
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1.  Primary:   Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1   [ Time Frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 ]

2.  Primary:   Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 1   [ Time Frame: Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 1 ]

3.  Primary:   Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 1   [ Time Frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 ]

4.  Primary:   Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 1   [ Time Frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 ]

5.  Primary:   Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 9   [ Time Frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9 ]

6.  Primary:   Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 9   [ Time Frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9 ]

7.  Primary:   Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 9   [ Time Frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9 ]

8.  Primary:   Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 15   [ Time Frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 15 ]

9.  Primary:   Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 15   [ Time Frame: Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 15 ]

10.  Primary:   Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC[0-168h]) of Vemurafenib on Day 15   [ Time Frame: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15 ]

11.  Primary:   Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15   [ Time Frame: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15 ]

12.  Primary:   Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 15   [ Time Frame: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15 ]

13.  Primary:   Apparent Clearance (CL/F) of Vemurafenib on Day 15   [ Time Frame: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15 ]

14.  Primary:   Terminal Elimination Half-Life (t1/2) of Vemurafenib on Day 15   [ Time Frame: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15 ]

15.  Primary:   Accumulation Ratio of Vemurafenib on Day 15   [ Time Frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 and 15 ]

16.  Secondary:   Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR)   [ Time Frame: Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13) ]

17.  Secondary:   Overall Survival (OS)   [ Time Frame: Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13) ]


  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
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  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: Medical Communications
Organization: Hoffmann-La Roche
phone: 800-821-8590
e-mail: genentech@druginfo.com


No publications provided by Hoffmann-La Roche

Publications automatically indexed to this study:

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01107418     History of Changes
Other Study ID Numbers: NP25163
Study First Received: April 12, 2010
Results First Received: July 29, 2015
Last Updated: July 29, 2015
Health Authority: United States: Food and Drug Administration