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Trial record 1 of 4 for:    19726763 [PUBMED-IDS]
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GDC-0449 in Treating Patients With Locally Advanced or Metastatic Solid Tumors

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ClinicalTrials.gov Identifier: NCT00607724
Recruitment Status : Completed
First Posted : February 6, 2008
Results First Posted : October 8, 2015
Last Update Posted : October 8, 2015
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Information provided by (Responsible Party):
Genentech, Inc.

Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Unspecified Adult Solid Tumor, Protocol Specific
Intervention: Drug: GDC-0449

  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
Stage 1: GDC-0449 (150 mg) Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 milligram (mg) on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 150 mg, orally, continuing until disease progression (deterioration of evaluable lesions and/or tumor-related symptoms defined using Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST v1.0), maximum benefit, or intolerability.
Stage 1: GDC-0449 (270 mg) Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 270 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Stage 1: GDC-0449 (540 mg) Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Stage 2: Basal Cell Carcinoma [GDC-0449 (150 mg)] Participants with basal cell carcinoma (BCC) received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Stage 2: Basal Cell Carcinoma [GDC-0449 (270 mg)] Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Stage 2:Safety Expansion Cohort [GDC-0449 (150 mg)] Participants received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Stage 2: New Formulation [GDC-0449 (150 mg )] Participants received a daily oral dose of GDC-0449 Phase II drug product hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.

Participant Flow for 2 periods

Period 1:   Stage 1: Dose Escalation
    Stage 1: GDC-0449 (150 mg)   Stage 1: GDC-0449 (270 mg)   Stage 1: GDC-0449 (540 mg)   Stage 2: Basal Cell Carcinoma [GDC-0449 (150 mg)]   Stage 2: Basal Cell Carcinoma [GDC-0449 (270 mg)]   Stage 2:Safety Expansion Cohort [GDC-0449 (150 mg)]   Stage 2: New Formulation [GDC-0449 (150 mg )]
STARTED   7   9   4   0   0   0   0 
COMPLETED   0   1 [1]   0   0   0   0   0 
NOT COMPLETED   7   8   4   0   0   0   0 
Tumour Progression−Clinical/Radiographic                7                8                4                0                0                0                0 
[1] Participants still on treatment at time of study closure were considered ‘completers’.

Period 2:   Stage 2: Expanded Cohort
    Stage 1: GDC-0449 (150 mg)   Stage 1: GDC-0449 (270 mg)   Stage 1: GDC-0449 (540 mg)   Stage 2: Basal Cell Carcinoma [GDC-0449 (150 mg)]   Stage 2: Basal Cell Carcinoma [GDC-0449 (270 mg)]   Stage 2:Safety Expansion Cohort [GDC-0449 (150 mg)]   Stage 2: New Formulation [GDC-0449 (150 mg )]
STARTED   0   0   0   6   14   12   16 
COMPLETED   0   0   0   1 [1]   5 [1]   0   5 [1] 
NOT COMPLETED   0   0   0   5   9   12   11 
Adverse Event                0                0                0                0                0                0                1 
Tumour Progression−Clinical/Radiographic                0                0                0                4                8                11                10 
Physician Decision                0                0                0                0                1                1                0 
Withdrawal by Subject                0                0                0                1                0                0                0 
[1] Participants still on treatment at time of study closure were considered ‘completers’.



  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.
Safety-evaluable population included all participants who received any amount of GDC-0449.

Reporting Groups
  Description
Stage 1: GDC-0449 (150 mg) Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 150 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Stage 1: GDC-0449 (270 mg) Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 270 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Stage 1: GDC-0449 (540 mg) Participants with any tumor received a single oral dose of GDC-0449 hard gelatin capsules at a dosage of 540 mg on Day 1. Beginning on Day 8, participants received once daily doses of GDC-0449 540 mg, orally, continuing until disease progression, maximum benefit, or intolerability.
Stage 2: Basal Cell Carcinoma [GDC-0449 (150 mg)] Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Stage 2: Basal Cell Carcinoma [GDC-0449 (270 mg)] Participants with BCC received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 270 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Stage 2:Safety Expansion Cohort [GDC-0449 (150 mg)] Participants received a daily oral dose of GDC-0449 hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability.
Stage 2: New Formulation [GDC-0449 (150 mg )] Participants received a daily oral dose of GDC-0449 Phase II drug product hard gelatin capsules at a dosage of 150 mg starting on Day 1 and continuing until disease progression, maximum benefit, or intolerability
Total Total of all reporting groups

Baseline Measures
   Stage 1: GDC-0449 (150 mg)   Stage 1: GDC-0449 (270 mg)   Stage 1: GDC-0449 (540 mg)   Stage 2: Basal Cell Carcinoma [GDC-0449 (150 mg)]   Stage 2: Basal Cell Carcinoma [GDC-0449 (270 mg)]   Stage 2:Safety Expansion Cohort [GDC-0449 (150 mg)]   Stage 2: New Formulation [GDC-0449 (150 mg )]   Total 
Overall Participants Analyzed 
[Units: Participants]
 7   9   4   6   14   12   16   68 
Age 
[Units: Years]
Mean (Standard Deviation)
 57.6  (10.5)   59.9  (12.6)   42.3  (15.3)   54.2  (15.3)   54.7  (11.2)   55.3  (14.8)   54.6  (11.0)   55.0  (12.6) 
Gender 
[Units: Participants]
               
Female   2   5   1   1   4   5   6   24 
Male   5   4   3   5   10   7   10   44 


  Outcome Measures

1.  Primary:   Percentage of Participants With Dose-Limiting Toxicities (DLTs)   [ Time Frame: Up to Week 6 ]

2.  Primary:   Maximum Observed Plasma Concentration (Cmax) After a Single Dose of GDC-0449   [ Time Frame: -5 minutes (pre-dose) and 0.5, 1, 2, 4, 8, 24 hours post-dose on Day 1; additionally for stage 1 arms: 48 hours (Day 3), 72 hours (Day 4) post-dose and – 5 minutes (pre-dose) on Day 8 ]

3.  Primary:   Cmax After Multiple Doses of GDC-0449   [ Time Frame: -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years ]

4.  Primary:   Time to Maximum Plasma Concentration (Tmax) After a Single Dose of GDC-0449   [ Time Frame: -5 minutes (pre-dose) and 0.5, 1, 2, 4, 8, 24 hours post-dose on Day 1; additionally for stage 1 arms: 48 hours (Day 3), 72 hours (Day 4) post-dose and – 5 minutes (pre-dose) on Day 8 ]

5.  Primary:   Tmax After Multiple Doses of GDC-0449   [ Time Frame: -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years ]

6.  Primary:   Average Plasma Concentration at Steady State (Css, Avg) After Multiple Doses of GDC-0449   [ Time Frame: -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years ]

7.  Primary:   Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) After a Single Dose of GDC-0449   [ Time Frame: -5 minutes (pre-dose) and 0.5, 1, 2, 4, 8, 24 hours post-dose on Day 1; additionally for stage 1 arms: 48 hours (Day 3), 72 hours (Day 4) post-dose and – 5 minutes (pre-dose) on Day 8 ]

8.  Primary:   AUC0-24 After Multiple Doses of GDC-0449   [ Time Frame: -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years ]

9.  Primary:   Accumulation Index (AI) After Multiple Doses of GDC-0449   [ Time Frame: -5 minutes (pre-dose), 0.5,1,2,4,8 hours post-dose on Day [D] 1; 2,3,4; -5 minutes (pre-dose) on D8,15,22,29,36,64,92,120,148,176,204,232,260,288,316,344;every 4 weeks after D345; end of treatment and study (up to 28 days after last dose), up to 2 years ]

10.  Secondary:   Percentage of Participants With a Greater Than (>) 2-Fold Down-Modulation of GLI1 Expression in Skin Biopsy-Derived or Hair Follicle-Derived Messenger Ribonucleic Acid (mRNA)   [ Time Frame: Baseline up to Day 29 ]

11.  Secondary:   Percentage of Participants With a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR): All Participants   [ Time Frame: Screening, at Week 8 thereafter every 8 weeks, up to Week 116 ]

12.  Secondary:   Percentage of Participants With a BOR of CR or PR: Participants With Basal Cell Carcinoma   [ Time Frame: Screening, at Week 8 thereafter every 8 weeks, up to Week 116 ]

13.  Secondary:   Duration of Objective Response: All Participants   [ Time Frame: Screening, at Week 8 thereafter every 8 weeks, up to Week 116 ]

14.  Secondary:   Duration of Objective Response: Participants With BCC   [ Time Frame: Screening, at Week 8 thereafter every 8 weeks, up to Week 116 ]

15.  Secondary:   Progression-Free Survival (PFS): All Participants   [ Time Frame: Screening, at Week 8 thereafter every 8 weeks, up to Week 116 ]

16.  Secondary:   PFS: Participants With BCC   [ Time Frame: Screening, at Week 8 thereafter every 8 weeks, up to Week 116 ]


  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 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-LaRoche
phone: 800-821-8590
e-mail: genentech@druginfo.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00607724     History of Changes
Obsolete Identifiers: NCT00862771
Other Study ID Numbers: CDR0000585468
JHOC-J06131
GENETECH-SHH3925g
First Submitted: January 31, 2008
First Posted: February 6, 2008
Results First Submitted: July 22, 2015
Results First Posted: October 8, 2015
Last Update Posted: October 8, 2015