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A Study of Vismodegib in Patients With Advanced Solid Malignancies Including Hepatocellular Carcinoma With Varying Degrees of Renal or Hepatic Function

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01546519
First received: March 2, 2012
Last updated: April 14, 2016
Last verified: April 2016
Results First Received: October 13, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Cancer
Intervention: Drug: Vismodegib

  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 was an open-label study with no randomization. Participants were categorized according to their baseline renal and hepatic function, and assigned to one of the five cohorts.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
After assessing the additional data since the study initiation and after discussions with regulators, the sponsor concluded that renal impairment does not impact the pharmacokinetics of vismodegib and, therefore, a dedicated renal impairment cohort was eliminated.

Reporting Groups
  Description
Control Cohort With Normal Renal and Normal Hepatic Function Participants with normal renal and normal hepatic function were included. Normal renal function was defined as Body Surface Area (BSA) - indexed creatinine clearance (CrCl) (mL/min) = / >= 60 Normal hepatic function was indicated by total bilirubin (TB) <= upper limit of normal (ULN) range and aspartate transaminase (AST) <= ULN Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.
Mild Hepatic Impairment and Normal Renal Function (Mild HI)

Participants with mild hepatic impairment and normal renal function were included.

Mild Hepatic was defined as = TB<=ULN, AST>ULN; OR ULN<TB<=1.5× ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60 Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.

Moderate Hepatic Impairment and Normal Renal Function (Mod HI)

Participants with moderate hepatic impairment and normal renal function were included.

Moderate hepatic impairment was defined as 1.5 × ULN< TB<3× ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60 Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.

Severe Hepatic Impairment and Normal Renal Function (Sev HI)

Participants with severe hepatic impairment and normal renal function were included.

Severe hepatic impairment is defined as 3×ULN<TB<10×ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60 Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.


Participant Flow:   Overall Study
    Control Cohort With Normal Renal and Normal Hepatic Function   Mild Hepatic Impairment and Normal Renal Function (Mild HI)   Moderate Hepatic Impairment and Normal Renal Function (Mod HI)   Severe Hepatic Impairment and Normal Renal Function (Sev HI)
STARTED   9   8   8   6 
Safety-Evaluable Participants   9   8   8   6 
COMPLETED   0   0   0   0 
NOT COMPLETED   9   8   8   6 
Adverse Event                0                0                1                1 
Death                0                1                3                1 
related to disease progression                2                2                2                1 
Physician Decision                6                5                2                3 
Withdrawal by Subject                1                0                0                0 



  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
Control Cohort With Normal Renal and Normal Hepatic Function

Participants with normal renal and normal hepatic function were included. Normal renal function was defined as Body Surface Area (BSA) - indexed creatinine clearance (CrCl) (mL/min) = / >= 60 Normal hepatic function was indicated by total bilirubin (TB) <= upper limit of normal (ULN) range and aspartate transaminase (AST) <= ULN.

Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.

Mild Hepatic Impairment and Normal Renal Function (Mild HI)

Participants with mild hepatic impairment and normal renal function were included.

Mild Hepatic was defined as = TB<=ULN, AST>ULN; OR ULN<TB<=1.5× ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.

Moderate Hepatic Impairment and Normal Renal Function (Mod HI)

Participants with moderate hepatic impairment and normal renal function were included.

Moderate hepatic impairment was defined as 1.5 × ULN< TB<3× ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.

Severe Hepatic Impairment and Normal Renal Function (Sev HI)

Participants with severe hepatic impairment and normal renal function were included.

Severe hepatic impairment is defined as 3×ULN<TB<10×ULN, AST any Normal renal function was defined as BSA - indexed CrCl (mL/min) = / >= 60. Participants were administered 150 mg oral vismodegib once daily for 8 consecutive days (Day 1 to Day 7 doses were taken with or without food; Day 8 dose was administered on an empty stomach) at approximately the same time with about 240 mL of water.

Total Total of all reporting groups

Baseline Measures
   Control Cohort With Normal Renal and Normal Hepatic Function   Mild Hepatic Impairment and Normal Renal Function (Mild HI)   Moderate Hepatic Impairment and Normal Renal Function (Mod HI)   Severe Hepatic Impairment and Normal Renal Function (Sev HI)   Total 
Overall Participants Analyzed 
[Units: Participants]
 9   8   8   6   31 
Age 
[Units: Years]
Mean (Standard Deviation)
 63.3  (12.6)   60.6  (14.1)   65.8  (10.7)   64.0  (8.4)   63.4  (11.4) 
Gender 
[Units: Participants]
         
Female   1   3   2   1   7 
Male   8   5   6   5   24 


  Outcome Measures
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1.  Primary:   Maximum Observed Plasma Concentration and Concentration at Steady-state Following Multiple Doses of Vismodegib   [ Time Frame: Day 1,2,4 and 0, 0.5, 1, 2, 4, 8 and 24 hours post dose on Day 8 ]

2.  Primary:   The Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC[0-24hours]) Following Multiple Doses of Vismodegib   [ Time Frame: Day 1, 2, 4 and 0, 0.5, 1, 2, 4, 8 and 24 hours postdose on Day 8 ]

3.  Secondary:   The Percentage of Dose of Vismodegib in 24-hour Total Urine   [ Time Frame: 24 hr total interval on Day 8 ]

4.  Secondary:   Renal Clearance of Vismodegib   [ Time Frame: 0, 0.5, 1, 2, 4, 8 and 24 hours postdose on Day 8 ]

5.  Secondary:   Amount of Vismodegib Excreted Into Urine in 24 Hours (Ae0-24hr)   [ Time Frame: 24 hr total interval on Day 8 ]

6.  Secondary:   Time to Maximum Plasma Concentration (Tmax) of Vismodegib   [ Time Frame: Up to 8 days ]

7.  Secondary:   Minimum Plasma Concentration (Cmin) of Vismodegib   [ Time Frame: Up to 8 days ]

8.  Secondary:   Apparent Clearance (CL/F) of Vismodegib   [ Time Frame: Up to 8 days ]

9.  Secondary:   Apparent Non-renal Clearance (CLNR/F) of Vismodegib   [ Time Frame: Up to 8 days ]


  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: Roche Trial Information Hotline
Organization: F. Hoffmann-La Roche AG
phone: +41 61 6878333
e-mail: global.trial_information@roche.com



Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01546519     History of Changes
Other Study ID Numbers: GP27839
Study First Received: March 2, 2012
Results First Received: October 13, 2015
Last Updated: April 14, 2016
Health Authority: United States: Food and Drug Administration