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Trial record 12 of 109 for:    hedgehog

A Study of Hedgehog Pathway Inhibitor GDC-0449 in Patients With Locally Advanced or Metastatic Solid Tumors That Are Refractory to Standard Therapy or for Whom No Standard Therapy Exists

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ClinicalTrials.gov Identifier: NCT00968981
Recruitment Status : Completed
First Posted : August 31, 2009
Results First Posted : December 9, 2015
Last Update Posted : July 11, 2017
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Solid Cancers
Intervention Drug: GDC-0449
Enrollment 67

Recruitment Details  
Pre-assignment Details  
Arm/Group Title GDC-0449 150 mg QD GDC-0449 150 mg TIW GDC-0449 150 mg QW
Hide Arm/Group Description Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule once daily (QD) orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QD orally from Day 15 to Day 57 (maintenance dose). Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule three times weekly (TIW) orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule TIW orally from Day 15 to Day 57 (maintenance dose). Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule once weekly (QW) orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QW orally from Day 15 to Day 57 (maintenance dose).
Period Title: Overall Study
Started 23 22 22
Pharmacokinetic(PK) Evaluable Population 20 [1] 21 [1] 22 [1]
Completed 1 0 0
Not Completed 22 22 22
Reason Not Completed
Adverse Event             2             0             0
Disease Progression             14             16             13
Lost to Follow-up             0             0             1
Physician Decision             5             3             5
Withdrawal by Subject             1             3             3
[1]
Participants with sufficient data to ensure reliable estimation of PK for at least Day 1 PK profile.
Arm/Group Title GDC-0449 150 mg QD GDC-0449 150 mg TIW GDC-0449 150 mg QW Total
Hide Arm/Group Description Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QD orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QD orally from Day 15 to Day 57 (maintenance dose). Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule TIW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule TIW orally from Day 15 to Day 57 (maintenance dose). Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QW orally from Day 15 to Day 57 (maintenance dose). Total of all reporting groups
Overall Number of Baseline Participants 23 22 22 67
Hide Baseline Analysis Population Description
All enrolled participants were included for baseline parameters.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 23 participants 22 participants 22 participants 67 participants
62.1  (10.4) 64.0  (12.3) 62.9  (10.3) 63.0  (10.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 22 participants 22 participants 67 participants
Female
10
  43.5%
9
  40.9%
10
  45.5%
29
  43.3%
Male
13
  56.5%
13
  59.1%
12
  54.5%
38
  56.7%
1.Primary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax) at Steady-State for Both Total and Unbound GDC-0449
Hide Description [Not Specified]
Time Frame Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PK Evaluable Population. Number of participants analyzed (N) is equal to (=) participants with baseline and at least one post-baseline assessment for this outcome; n = participants evaluable at specified time-points.
Arm/Group Title GDC-0449 150 mg QD GDC-0449 150 mg TIW GDC-0449 150 mg QW
Hide Arm/Group Description:
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QD orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QD orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule TIW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule TIW orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QW orally from Day 15 to Day 57 (maintenance dose).
Overall Number of Participants Analyzed 15 18 18
Median (Full Range)
Unit of Measure: hours
Total: Days 29-36 (n=15,18,18)
24
(1 to 168)
72
(0 to 96)
15
(1 to 96)
Total: Days 50-57 (n=11,13,10)
74
(4 to 164)
74
(4 to 164)
24
(4 to 74)
Unbound; Days 29-36 (n=15, 18, 18)
24
(0 to 168)
6
(0 to 168)
6
(1 to 72)
Unbound: Days 50-57 (n=11,13,10)
104
(4 to 164)
94
(4 to 104)
4
(4 to 74)
2.Primary Outcome
Title Number of Participants With Greater Than (>) 50 Percent (%) Decrease in Trough Concentration at Steady State (Css, Trough)
Hide Description Percent change = ([trough concentration on Day 15 minus trough concentration on Day 57] divided by trough concentration on Day 15) multiplied by 100.
Time Frame Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Evaluable Population. Here number of participants analyzed (N) = participants with baseline and at least 1 post baseline assessment for this outcome.
Arm/Group Title GDC-0449 150 mg QD GDC-0449 150 mg TIW GDC-0449 150 mg QW
Hide Arm/Group Description:
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QD orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QD orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule TIW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule TIW orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QW orally from Day 15 to Day 57 (maintenance dose).
Overall Number of Participants Analyzed 7 13 9
Measure Type: Number
Unit of Measure: participants
Total GDC−0449 0 1 4
Unbound GDC−0449 0 6 9
3.Primary Outcome
Title Ratio of Total and Unbound Trough GDC-0449 Concentration Between Day 57 to Day 15
Hide Description Ratio = trough concentration on Day 57 divided by trough concentration on Day 15. If the ratio of total and unbound trough GDC-0449 concentration between Day 57 to Day 15 is less than 1, then it indicates reduction in total and unbound trough GDC-0449 concentration between Day 15 to Day 57.
Time Frame Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PK Evaluable Population. N = participants who completed Day 57 of the study were included in this analysis.
Arm/Group Title GDC-0449 150 mg QD GDC-0449 150 mg TIW GDC-0449 150 mg QW
Hide Arm/Group Description:
Single dose of GDC­0449 150 mg capsule orally on Day 1 and then one capsule QD orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QD orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule TIW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule TIW orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QW orally from Day 15 to Day 57 (maintenance dose).
Overall Number of Participants Analyzed 7 13 9
Mean (Full Range)
Unit of Measure: ratio
Css,trough for Total GDC-0449
1.23
(1.01 to 1.73)
0.87
(0.49 to 1.27)
0.54
(0.47 to 0.66)
Css,trough for Unbound GDC-0449
1.34
(0.96 to 2.21)
0.58
(0.28 to 1.49)
0.20
(0.11 to 0.35)
4.Primary Outcome
Title Plasma Concentration at Steady State (Css) for Total and Unbound GDC−0449
Hide Description Plasma GDC-0449 concentrations were reported in nanogram per milliliter (ng/mL) units and converted to micromolar (mcM) units using the molecular weight (421.30 grams per mole [g/mol]) prior to PK analysis. Css was calculated for Days 28 to 56.
Time Frame Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Evaluable Population. N = participants with baseline and post baseline data available for measurement of Css at steady state.
Arm/Group Title GDC-0449 150 mg QD GDC-0449 150 mg TIW GDC-0449 150 mg QW
Hide Arm/Group Description:
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QD orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QD orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule TIW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule TIW orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QW orally from Day 15 to Day 57 (maintenance dose).
Overall Number of Participants Analyzed 15 18 18
Mean (Standard Deviation)
Unit of Measure: mcM
Total GDC−0449 28  (11.4) 26.1  (11.8) 16.9  (5.89)
Unbound GDC−0449 0.163  (0.056) 0.088  (0.0408) 0.0489  (0.0259)
5.Primary Outcome
Title Maximum Plasma Concentration (Cmax) of Total and Unbound GDC−0449
Hide Description Plasma GDC-0449 concentrations were reported in ng/mL units and converted to mcM units using the molecular weight (421.30 g/mol) prior to PK analysis.
Time Frame 0, 1, 2, 4, 6, 24, 48, 72 hours on Day 1, 15 and 57 post-dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Evaluable Population. 'n' signifies number of participants with data available at specified timepoint in each group.
Arm/Group Title GDC-0449 150 mg QD GDC-0449 150 mg TIW GDC-0449 150 mg QW
Hide Arm/Group Description:
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QD orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QD orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule TIW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule TIW orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QW orally from Day 15 to Day 57 (maintenance dose).
Overall Number of Participants Analyzed 20 21 22
Mean (Standard Deviation)
Unit of Measure: mcM
Cmax,Total GDC−0449: Single Dose (n=20,21,22) 7.09  (3.66) 8.08  (3.48) 7.29  (3.24)
Cmax,Total GDC−0449: Day 29-36 (n=15,18,18) 30.4  (11.6) 29.5  (12.6) 21.2  (5.59)
Cmax,Total GDC−0449: Day 50-57 (n=11,13,10) 33.9  (12.2) 28.6  (13.8) 18.2  (4.23)
Cmax,Unbound GDC−0449: Single Dose (n=20,21,22) 0.02  (0.02) 0.02  (0.02) 0.02  (0.01)
Cmax,Unbound GDC−0449:Day 29-36 (n=15,18,18) 0.215  (0.0797) 0.122  (0.0602) 0.0998  (0.0516)
Cmax,Unbound GDC−0449:Day 50-57 (n=11,13,10) 0.247  (0.0841) 0.132  (0.0717) 0.0688  (0.0312)
6.Primary Outcome
Title Area Under the Curve From Time Zero to 24 Hour (AUC0-24) for Total and Unbound GDC-0449
Hide Description AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. AUC values were calculated using the linear trapezoidal method when the concentrations were rising and using the logarithmic trapezoidal method when the concentrations were declining (linear up/log down rule in WinNonlin). Below the limit of quantitation (BLQ) values at pre-dose were considered as zero for PK analysis.
Time Frame Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Evaluable Population. n = number of participants with data available at specified timepoint in each group.
Arm/Group Title GDC-0449 150 mg QD GDC-0449 150 mg TIW GDC-0449 150 mg QW
Hide Arm/Group Description:
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QD orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QD orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule TIW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule TIW orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QW orally from Day 15 to Day 57 (maintenance dose).
Overall Number of Participants Analyzed 20 21 22
Mean (Standard Deviation)
Unit of Measure: mcM*hour
AUC0-24,Total GDC−0449: Single Dose (n=20,21,22) 130.88  (73.69) 129.44  (71.66) 126.05  (61.73)
AUC0-24,Total GDC−0449: Day 29 (n=14,17,18) 696  (258) 595  (241) 455  (116)
AUC0-24,Total GDC−0449: Day 50 (n=11,13,9) 729  (251) 587  (274) 387  (86)
AUC0-24,Unbound GDC−0449: Single Dose (n=20,21,22) 0.38  (0.31) 0.30  (0.27) 0.32  (0.20)
AUC0-24,Unbound GDC−0449:Day 29 (n=14,17,17) 4.06  (1.13) 2.39  (1.29) 1.81  (0.958)
AUC0-24,Unbound GDC−0449:Day 50 (n=11,13,9) 4.8  (1.75) 2.44  (1.19) 1.51  (0.615)
7.Primary Outcome
Title Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) for Total and Unbound GDC-0449
Hide Description AUC values were calculated using the linear trapezoidal method when the concentrations were rising and using the logarithmic trapezoidal method when the concentrations were declining (linear up/log down rule in WinNonlin). BLQ values at pre-dose were considered as zero for PK analysis.
Time Frame Predose and 1, 2, 4, 6, 24, 48, and 72 on Days 1, 29, 50, and 54 and predose on Days 8, 10, 15, 22, 33, 36, 43, and 57
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Evaluable Population. n = number of participants with data available at specified time point in each group.
Arm/Group Title GDC-0449 150 mg QD GDC-0449 150 mg TIW GDC-0449 150 mg QW
Hide Arm/Group Description:
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QD orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QD orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule TIW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule TIW orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QW orally from Day 15 to Day 57 (maintenance dose).
Overall Number of Participants Analyzed 20 21 22
Mean (Standard Deviation)
Unit of Measure: mcM*hour
AUClast,Total GDC−0449: Single Dose (n=20,21,22) 431.20  (201.18) 478.38  (212.88) 453.14  (209.48)
AUClast,Total GDC−0449: Day 28-35 (n=14,14,18) 4834.06  (1708.27) 4302.84  (1691.87) 2935.33  (926.74)
AUClast,Total GDC−0449: Day 49-56 (n=9,13,9) 5235.09  (2010.93) 4074.88  (1779.33) 2656.65  (666.09)
AUClast,Unbound GDC−0449: Single Dose (n=20,21,22) 1.19  (0.73) 1.08  (0.82) 1.09  (0.65)
AUClast,Unbound GDC−0449:Day 28-35 (n=14,17,17) 28.32  (8.37) 15.69  (7.79) 10.50  (6.08)
AUClast,Unbound GDC−0449:Day 49-56 (n=8,13,9) 33.40  (11.91) 15.57  (6.52) 8.76  (3.23)
8.Primary Outcome
Title Time to Achieve Maximum Observed Plasma Concentration (Tmax) After a Single Dose of GDC-0449
Hide Description [Not Specified]
Time Frame 0, 1, 2, 4, 6, 24, 48, 72 hours on Day 1
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PK Evaluable Population.
Arm/Group Title GDC-0449 150 mg: All Participants
Hide Arm/Group Description:
All participants received single dose of GDC-0449 150 mg capsule orally on Day 1.
Overall Number of Participants Analyzed 63
Median (Full Range)
Unit of Measure: hours
Total GDC−0449
48
(1 to 72)
Unbound GDC−0449
48
(1 to 72)
9.Secondary Outcome
Title Percentage of Participants With Disease Progression or Death
Hide Description Disease progression (assessed by Response Evaluation Criteria in Solid Tumors [RECIST]) was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions or the appearance of one or more new lesions and/or unequivocal progression of existing non target lesions.
Time Frame Screening, Day 57, and every 8 weeks thereafter up to 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy Evaluable Population: all participants who had measurable disease at baseline and either had at least one follow-up tumor assessment or discontinued the study due to disease progression.
Arm/Group Title GDC-0449 150 mg QD GDC-0449 150 mg TIW GDC-0449 150 mg QW
Hide Arm/Group Description:
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QD orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QD orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule TIW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule TIW orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QW orally from Day 15 to Day 57 (maintenance dose).
Overall Number of Participants Analyzed 17 20 20
Measure Type: Number
Unit of Measure: percentage of participants
52.9 75.0 40.0
10.Secondary Outcome
Title Percentage of Participants With a Response by Best Overall Response (BOR)
Hide Description BOR was defined as the best overall response observed during the treatment period according to RECIST. CR: disappearance of all TLs, with any pathological lymph nodes (whether target or non-target) having a reduction in short axis to less than 10 mm. PR: at least a 30% decrease in the sum of diameters of TLs, taking as reference the BL sum diameters. Progressive disease (PD): at least a 20% increase in the sum of diameters of TLs, taking as a reference the smallest sum on study (this included the baseline sum if that is the smallest on study). In addition to the relative increase in 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Stable disease (SD) was defined as neither sufficient shrinkages to qualify for PR, nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time Frame Screening Day 57, and every 8 weeks thereafter up to 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy Evaluable Population; only participants with measurable disease at baseline were included in the analysis.
Arm/Group Title GDC-0449 150 mg QD GDC-0449 150 mg TIW GDC-0449 150 mg QW
Hide Arm/Group Description:
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QD orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QD orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule TIW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule TIW orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QW orally from Day 15 to Day 57 (maintenance dose).
Overall Number of Participants Analyzed 13 18 15
Measure Type: Number
Unit of Measure: percentage of participants
Complete Response 0.0 0.0 0.0
Partial Response 7.7 0.0 0.0
Stable Disease 30.8 22.2 53.3
Progressive Disease 61.5 77.8 40.0
Unevaluable (UE) 0.0 0.0 6.7
11.Secondary Outcome
Title Progression-Free Survival (PFS) Time
Hide Description PFS defined as the time from study treatment initiation to the first occurrence of disease progression, as determined by the investigator review of tumor assessments using RECIST, or death from any cause during the study (i.e., within 30 days after the last dose of study treatment).
Time Frame Screening Day 57, and every 8 weeks thereafter up to 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy Evaluable Population.
Arm/Group Title GDC-0449 150 mg QD GDC-0449 150 mg TIW GDC-0449 150 mg QW
Hide Arm/Group Description:
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QD orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QD orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule TIW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule TIW orally from Day 15 to Day 57 (maintenance dose).
Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QW orally from Day 15 to Day 57 (maintenance dose).
Overall Number of Participants Analyzed 17 20 20
Median (95% Confidence Interval)
Unit of Measure: months
1.9
(1.45 to 2.04)
1.9
(1.84 to 1.97)
2.2
(1.74 to 4.01)
12.Secondary Outcome
Title Duration of Response (DR)
Hide Description DR during first line therapy is defined as the time from when response (complete response [CR] or partial response [PR]) was first documented to first documented disease progression or death (whichever occurs first) during first line therapy. This was only be calculated for participants who achieved a best overall response of CR or PR. Participants who did not progress or die after they had a confirmed response were censored at the date of their last tumor measurement or last follow up for progression of disease during first line therapy. CR: disappearance of all target lesions (TLs) with any pathological lymph nodes (whether target or non-target) having a reduction in short axis to less than 10 millimeters. PR: at least a 30% decrease in the sum of diameters of TLs, with reference to baseline sum diameters. DR was not calculated as only 1 responding participant reached their response at the last scheduled response assessment, hence follow-up data are not available.
Time Frame Screening Day 57, and every 8 weeks thereafter up to 52 weeks
Outcome Measure Data Not Reported
Time Frame From signature of informed consent up to 30 days after last dose of study medication (maximum 57 days on study medication).
Adverse Event Reporting Description Safety Population included all participants who received at least 1 dose of study medication.
 
Arm/Group Title GDC-0449 150 mg QD GDC-0449 150 mg TIW GDC-0449 150 mg QW
Hide Arm/Group Description Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QD orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QD orally from Day 15 to Day 57 (maintenance dose). Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule TIW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule TIW orally from Day 15 to Day 57 (maintenance dose). Single dose of GDC-0449 150 mg capsule orally on Day 1 and then one capsule QW orally from Day 4 to Day 14 (loading dose) followed by 150 mg capsule QW orally from Day 15 to Day 57 (maintenance dose).
All-Cause Mortality
GDC-0449 150 mg QD GDC-0449 150 mg TIW GDC-0449 150 mg QW
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
GDC-0449 150 mg QD GDC-0449 150 mg TIW GDC-0449 150 mg QW
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/20 (30.00%)   8/21 (38.10%)   8/22 (36.36%) 
Gastrointestinal disorders       
Intestinal obstruction * 1  3/20 (15.00%)  0/21 (0.00%)  0/22 (0.00%) 
Small intestinal obstruction * 1  1/20 (5.00%)  0/21 (0.00%)  1/22 (4.55%) 
Abdominal pain upper * 1  0/20 (0.00%)  0/21 (0.00%)  1/22 (4.55%) 
Constipation * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Jejunal ulcer * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Ileus paralytic * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Gastrointestinal haemorrhage * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Upper gastrointestinal haemorrhage * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
General disorders       
Gait disturbance * 1  0/20 (0.00%)  0/21 (0.00%)  1/22 (4.55%) 
Pain * 1  0/20 (0.00%)  1/21 (4.76%)  0/22 (0.00%) 
Infections and infestations       
Urosepsis * 1  0/20 (0.00%)  2/21 (9.52%)  0/22 (0.00%) 
Abdominal wall abscess * 1  0/20 (0.00%)  1/21 (4.76%)  0/22 (0.00%) 
Pneumonia * 1  0/20 (0.00%)  0/21 (0.00%)  1/22 (4.55%) 
Cystitis * 1  0/20 (0.00%)  0/21 (0.00%)  1/22 (4.55%) 
Injury, poisoning and procedural complications       
Thoracic vertebral fracture * 1  0/20 (0.00%)  0/21 (0.00%)  1/22 (4.55%) 
Metabolism and nutrition disorders       
Dehydration * 1  1/20 (5.00%)  0/21 (0.00%)  1/22 (4.55%) 
Musculoskeletal and connective tissue disorders       
Back pain * 1  0/20 (0.00%)  0/21 (0.00%)  1/22 (4.55%) 
Nervous system disorders       
Headache * 1  0/20 (0.00%)  1/21 (4.76%)  0/22 (0.00%) 
Spinal cord compression * 1  0/20 (0.00%)  1/21 (4.76%)  0/22 (0.00%) 
Psychiatric disorders       
Mental status changes * 1  0/20 (0.00%)  1/21 (4.76%)  0/22 (0.00%) 
Renal and urinary disorders       
Renal failure acute * 1  0/20 (0.00%)  1/21 (4.76%)  0/22 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Chronic obstructive pulmonary disease * 1  0/20 (0.00%)  1/21 (4.76%)  0/22 (0.00%) 
Vascular disorders       
Lymphoedema * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (13.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
GDC-0449 150 mg QD GDC-0449 150 mg TIW GDC-0449 150 mg QW
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   19/20 (95.00%)   19/21 (90.48%)   20/22 (90.91%) 
Blood and lymphatic system disorders       
Anaemia * 1  4/20 (20.00%)  4/21 (19.05%)  2/22 (9.09%) 
Thrombocytopenia * 1  0/20 (0.00%)  2/21 (9.52%)  1/22 (4.55%) 
Iron deficiency anaemia * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Paratracheal lymphadenopathy * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Cardiac disorders       
Tachycardia * 1  1/20 (5.00%)  2/21 (9.52%)  1/22 (4.55%) 
Sinus bradycardia * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Ear and labyrinth disorders       
Ear congestion * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Endocrine disorders       
Adrenal insufficiency * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Eye disorders       
Conjunctivitis * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Photopsia * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Visual impairment * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Gastrointestinal disorders       
Nausea * 1  11/20 (55.00%)  8/21 (38.10%)  8/22 (36.36%) 
Vomiting * 1  7/20 (35.00%)  3/21 (14.29%)  8/22 (36.36%) 
Abdominal pain * 1  3/20 (15.00%)  4/21 (19.05%)  6/22 (27.27%) 
Abdominal pain upper * 1  3/20 (15.00%)  3/21 (14.29%)  5/22 (22.73%) 
Constipation * 1  4/20 (20.00%)  2/21 (9.52%)  4/22 (18.18%) 
Diarrhoea * 1  4/20 (20.00%)  1/21 (4.76%)  2/22 (9.09%) 
Dysphagia * 1  3/20 (15.00%)  1/21 (4.76%)  1/22 (4.55%) 
Abdominal discomfort * 1  1/20 (5.00%)  1/21 (4.76%)  2/22 (9.09%) 
Abdominal distension * 1  2/20 (10.00%)  1/21 (4.76%)  1/22 (4.55%) 
Ascites * 1  3/20 (15.00%)  0/21 (0.00%)  1/22 (4.55%) 
Abdominal pain lower * 1  2/20 (10.00%)  0/21 (0.00%)  1/22 (4.55%) 
Dry mouth * 1  0/20 (0.00%)  0/21 (0.00%)  3/22 (13.64%) 
Dyspepsia * 1  1/20 (5.00%)  1/21 (4.76%)  1/22 (4.55%) 
Flatulence * 1  1/20 (5.00%)  1/21 (4.76%)  1/22 (4.55%) 
Faeces hard * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Gastrooesophageal reflux disease * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Hypoaesthesia oral * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Rectal haemorrhage * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Stomatitis * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Tongue ulceration * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
General disorders       
Fatigue * 1  8/20 (40.00%)  8/21 (38.10%)  9/22 (40.91%) 
Oedema peripheral * 1  3/20 (15.00%)  2/21 (9.52%)  3/22 (13.64%) 
Pain * 1  1/20 (5.00%)  3/21 (14.29%)  1/22 (4.55%) 
Early satiety * 1  4/20 (20.00%)  0/21 (0.00%)  0/22 (0.00%) 
Chest pain * 1  0/20 (0.00%)  2/21 (9.52%)  1/22 (4.55%) 
Chills * 1  0/20 (0.00%)  2/21 (9.52%)  1/22 (4.55%) 
Pyrexia * 1  1/20 (5.00%)  0/21 (0.00%)  2/22 (9.09%) 
Asthenia * 1  1/20 (5.00%)  1/21 (4.76%)  0/22 (0.00%) 
Catheter site pain * 1  1/20 (5.00%)  1/21 (4.76%)  0/22 (0.00%) 
Gait disturbance * 1  1/20 (5.00%)  0/21 (0.00%)  1/22 (4.55%) 
Oedema * 1  2/20 (10.00%)  0/21 (0.00%)  0/22 (0.00%) 
Suprapubic pain * 1  1/20 (5.00%)  0/21 (0.00%)  1/22 (4.55%) 
Mucosal inflammation * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Non−cardiac chest pain * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Swelling * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Hepatobiliary disorders       
Jaundice * 1  0/20 (0.00%)  2/21 (9.52%)  0/22 (0.00%) 
Infections and infestations       
Urinary tract infection * 1  0/20 (0.00%)  3/21 (14.29%)  2/22 (9.09%) 
Candidiasis * 1  1/20 (5.00%)  0/21 (0.00%)  1/22 (4.55%) 
Infection * 1  0/20 (0.00%)  2/21 (9.52%)  0/22 (0.00%) 
Oral herpes * 1  0/20 (0.00%)  0/21 (0.00%)  2/22 (9.09%) 
Pneumonia * 1  0/20 (0.00%)  0/21 (0.00%)  2/22 (9.09%) 
Herpes zoster * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Skin candida * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Injury, poisoning and procedural complications       
Fall * 1  0/20 (0.00%)  2/21 (9.52%)  3/22 (13.64%) 
Drug toxicity * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Investigations       
Weight decreased * 1  4/20 (20.00%)  4/21 (19.05%)  5/22 (22.73%) 
Blood alkaline phosphatase increased * 1  1/20 (5.00%)  5/21 (23.81%)  2/22 (9.09%) 
Aspartate aminotransferase increased * 1  0/20 (0.00%)  4/21 (19.05%)  2/22 (9.09%) 
Blood lactate dehydrogenase increased * 1  0/20 (0.00%)  2/21 (9.52%)  3/22 (13.64%) 
Alanine aminotransferase increased * 1  0/20 (0.00%)  1/21 (4.76%)  2/22 (9.09%) 
Blood creatinine increased * 1  1/20 (5.00%)  0/21 (0.00%)  1/22 (4.55%) 
Blood chloride decreased * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Body temperature increased * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Breath sounds abnormal * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
White blood cell count increased * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite * 1  6/20 (30.00%)  6/21 (28.57%)  5/22 (22.73%) 
Dehydration * 1  3/20 (15.00%)  3/21 (14.29%)  4/22 (18.18%) 
Hypokalaemia * 1  1/20 (5.00%)  2/21 (9.52%)  0/22 (0.00%) 
Hypercalcaemia * 1  1/20 (5.00%)  1/21 (4.76%)  0/22 (0.00%) 
Hyperglycaemia * 1  1/20 (5.00%)  1/21 (4.76%)  0/22 (0.00%) 
Hypoalbuminaemia * 1  1/20 (5.00%)  0/21 (0.00%)  1/22 (4.55%) 
Hyponatraemia * 1  1/20 (5.00%)  0/21 (0.00%)  1/22 (4.55%) 
Hypocalcaemia * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Musculoskeletal and connective tissue disorders       
Muscle spasms * 1  6/20 (30.00%)  3/21 (14.29%)  5/22 (22.73%) 
Back pain * 1  3/20 (15.00%)  2/21 (9.52%)  4/22 (18.18%) 
Musculoskeletal chest pain * 1  4/20 (20.00%)  1/21 (4.76%)  3/22 (13.64%) 
Musculoskeletal pain * 1  1/20 (5.00%)  2/21 (9.52%)  2/22 (9.09%) 
Myalgia * 1  0/20 (0.00%)  1/21 (4.76%)  4/22 (18.18%) 
Arthralgia * 1  2/20 (10.00%)  2/21 (9.52%)  0/22 (0.00%) 
Neck pain * 1  1/20 (5.00%)  1/21 (4.76%)  2/22 (9.09%) 
Muscular weakness * 1  1/20 (5.00%)  1/21 (4.76%)  0/22 (0.00%) 
Pain in extremity * 1  1/20 (5.00%)  0/21 (0.00%)  1/22 (4.55%) 
Musculoskeletal stiffness * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Tumour associated fever * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Nervous system disorders       
Dizziness * 1  3/20 (15.00%)  2/21 (9.52%)  3/22 (13.64%) 
Headache * 1  1/20 (5.00%)  3/21 (14.29%)  3/22 (13.64%) 
Dysgeusia * 1  2/20 (10.00%)  4/21 (19.05%)  0/22 (0.00%) 
Hypogeusia * 1  2/20 (10.00%)  0/21 (0.00%)  0/22 (0.00%) 
Sinus headache * 1  0/20 (0.00%)  0/21 (0.00%)  2/22 (9.09%) 
Hypoaesthesia * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Neuropathy peripheral * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Poor quality sleep * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Psychiatric disorders       
Depression * 1  1/20 (5.00%)  2/21 (9.52%)  1/22 (4.55%) 
Insomnia * 1  0/20 (0.00%)  1/21 (4.76%)  3/22 (13.64%) 
Anxiety * 1  1/20 (5.00%)  0/21 (0.00%)  1/22 (4.55%) 
Confusional state * 1  0/20 (0.00%)  2/21 (9.52%)  0/22 (0.00%) 
Renal and urinary disorders       
Dysuria * 1  1/20 (5.00%)  1/21 (4.76%)  1/22 (4.55%) 
Chromaturia * 1  0/20 (0.00%)  2/21 (9.52%)  0/22 (0.00%) 
Haematuria * 1  1/20 (5.00%)  0/21 (0.00%)  1/22 (4.55%) 
Urinary retention * 1  1/20 (5.00%)  0/21 (0.00%)  1/22 (4.55%) 
Respiratory, thoracic and mediastinal disorders       
Cough * 1  4/20 (20.00%)  5/21 (23.81%)  4/22 (18.18%) 
Dyspnoea * 1  1/20 (5.00%)  6/21 (28.57%)  4/22 (18.18%) 
Hypoxia * 1  1/20 (5.00%)  1/21 (4.76%)  2/22 (9.09%) 
Dyspnoea exertional * 1  3/20 (15.00%)  0/21 (0.00%)  0/22 (0.00%) 
Oropharyngeal pain * 1  1/20 (5.00%)  1/21 (4.76%)  1/22 (4.55%) 
Tachypnoea * 1  1/20 (5.00%)  0/21 (0.00%)  1/22 (4.55%) 
Atelectasis * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Hiccups * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Upper−airway cough syndrome * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Skin and subcutaneous tissue disorders       
Pruritus * 1  2/20 (10.00%)  1/21 (4.76%)  0/22 (0.00%) 
Rash * 1  1/20 (5.00%)  1/21 (4.76%)  1/22 (4.55%) 
Decubitus ulcer * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Petechiae * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Skin lesion * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Subcutaneous nodule * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Vascular disorders       
Hypotension * 1  2/20 (10.00%)  1/21 (4.76%)  0/22 (0.00%) 
Hypertension * 1  1/20 (5.00%)  0/21 (0.00%)  1/22 (4.55%) 
Deep vein thrombosis * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
Lymphoedema * 1  1/20 (5.00%)  0/21 (0.00%)  0/22 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (13.1)
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 Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-LaRoche
Phone: 800-821-8590
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00968981     History of Changes
Other Study ID Numbers: SHH4610g
First Submitted: August 28, 2009
First Posted: August 31, 2009
Results First Submitted: July 9, 2015
Results First Posted: December 9, 2015
Last Update Posted: July 11, 2017