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
Sponsor
Genentech, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00968981
Collaborator
(none)
67
3
13
Study Details
Study Description
Brief Summary
This is a two stage, Phase Ib study designed to describe the pharmacokinetics of GDC-0449 in patients with advanced solid tumors that are refractory to treatment or for whom no standard therapy exists.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
67 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib, Open-Label, Dose-Scheduling 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
Actual Study Start Date
:
Sep 1, 2009
Actual Primary Completion Date
:
Oct 1, 2010
Actual Study Completion Date
:
Oct 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A
|
Drug: GDC-0449
Daily oral repeating dose
|
| Experimental: B
|
Drug: GDC-0449
Three times weekly oral repeating dose
|
| Experimental: C
|
Drug: GDC-0449
Once weekly oral repeating dose
|
Outcome Measures
Primary Outcome Measures
- Time to Reach Maximum Observed Plasma Concentration (Tmax) at Steady-State for Both Total and Unbound GDC-0449 [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]
- Number of Participants With Greater Than (>) 50 Percent (%) Decrease in Trough Concentration at Steady State (Css, Trough) [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]
Percent change = ([trough concentration on Day 15 minus trough concentration on Day 57] divided by trough concentration on Day 15) multiplied by 100.
- Ratio of Total and Unbound Trough GDC-0449 Concentration Between Day 57 to Day 15 [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]
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.
- Plasma Concentration at Steady State (Css) for Total and Unbound GDC-0449 [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]
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.
- Maximum Plasma Concentration (Cmax) of Total and Unbound GDC-0449 [0, 1, 2, 4, 6, 24, 48, 72 hours on Day 1, 15 and 57 post-dose]
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.
- Area Under the Curve From Time Zero to 24 Hour (AUC0-24) for Total and Unbound GDC-0449 [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]
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.
- Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) for Total and Unbound GDC-0449 [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]
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 to Achieve Maximum Observed Plasma Concentration (Tmax) After a Single Dose of GDC-0449 [0, 1, 2, 4, 6, 24, 48, 72 hours on Day 1]
Secondary Outcome Measures
- Percentage of Participants With Disease Progression or Death [Screening, Day 57, and every 8 weeks thereafter up to 52 weeks]
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.
- Percentage of Participants With a Response by Best Overall Response (BOR) [Screening Day 57, and every 8 weeks thereafter up to 52 weeks]
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.
- Progression-Free Survival (PFS) Time [Screening Day 57, and every 8 weeks thereafter up to 52 weeks]
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).
- Duration of Response (DR) [Screening Day 57, and every 8 weeks thereafter up to 52 weeks]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria
-
Histologically documented, incurable, locally advanced or metastatic solid malignancy that has progressed after first-line and second-line therapy (if there is a second-line therapy that has been shown to provide clinical benefit); patients with basal cell carcinoma will be excluded from this study unless they do not qualify for another open GDC-0449 clinical trial
-
For patients with disease that is evaluable by physical examination only, diagnosis must also include biomarker confirmation
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
-
Documented negative pregnancy test for women of childbearing potential and agreement to use an effective form of contraception for the duration of the study
-
Adequate hematopoietic capacity
-
Adequate hepatic function
-
Adequate renal function
-
At least 3 weeks since last chemotherapy, investigational agent, radiation therapy, or major surgical procedure and recovery to pre-treatment baseline or stabilization of all treatment-related toxicities
Exclusion Criteria
-
Known, untreated central nervous system (CNS) malignancies or treated brain metastases that are not radiographically stable for ≥ 3 months
-
Active infection requiring intravenous (IV) antibiotics
-
Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with hepatitis
-
Any medical condition or diagnosis that would likely impair absorption of an orally administered drug (e.g., gastrectomy, ileal bypass, chronic diarrhea, gastroparesis)
-
Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications
-
Pregnant or lactating
-
Treatment with excluded medications, including strong CYP450 inhibitors and inducers
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Genentech, Inc.
Investigators
- Study Director: Jennifer Low, M.D., Genentech, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT00968981
Other Study ID Numbers:
- SHH4610g
First Posted:
Aug 31, 2009
Last Update Posted:
Jul 11, 2017
Last Verified:
Jun 1, 2017
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | GDC-0449 150 mg QD | GDC-0449 150 mg TIW | GDC-0449 150 mg QW |
|---|---|---|---|
| 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 | 21 | 22 |
| COMPLETED | 1 | 0 | 0 |
| NOT COMPLETED | 22 | 22 | 22 |
Baseline Characteristics
| Arm/Group Title | GDC-0449 150 mg QD | GDC-0449 150 mg TIW | GDC-0449 150 mg QW | Total |
|---|---|---|---|---|
| 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 Participants | 23 | 22 | 22 | 67 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
62.1
(10.4)
|
64.0
(12.3)
|
62.9
(10.3)
|
63.0
(10.9)
|
| Sex: Female, Male (Count of 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%
|
Outcome Measures
| Title | Percentage of Participants With Disease Progression or Death |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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). |
| Measure Participants | 17 | 20 | 20 |
| Number [percentage of participants] |
52.9
230%
|
75.0
340.9%
|
40.0
181.8%
|
| Title | Percentage of Participants With a Response by Best Overall Response (BOR) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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). |
| Measure Participants | 13 | 18 | 15 |
| Complete Response |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Partial Response |
7.7
33.5%
|
0.0
0%
|
0.0
0%
|
| Stable Disease |
30.8
133.9%
|
22.2
100.9%
|
53.3
242.3%
|
| Progressive Disease |
61.5
267.4%
|
77.8
353.6%
|
40.0
181.8%
|
| Unevaluable (UE) |
0.0
0%
|
0.0
0%
|
6.7
30.5%
|
| Title | Progression-Free Survival (PFS) Time |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Evaluable Population. |
| Arm/Group Title | GDC-0449 150 mg QD | GDC-0449 150 mg TIW | GDC-0449 150 mg QW |
|---|---|---|---|
| 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). |
| Measure Participants | 17 | 20 | 20 |
| Median (95% Confidence Interval) [months] |
1.9
|
1.9
|
2.2
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) at Steady-State for Both Total and Unbound GDC-0449 |
|---|---|
| Description | |
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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). |
| Measure Participants | 15 | 18 | 18 |
| Total: Days 29-36 (n=15,18,18) |
24
|
72
|
15
|
| Total: Days 50-57 (n=11,13,10) |
74
|
74
|
24
|
| Unbound; Days 29-36 (n=15, 18, 18) |
24
|
6
|
6
|
| Unbound: Days 50-57 (n=11,13,10) |
104
|
94
|
4
|
| Title | Number of Participants With Greater Than (>) 50 Percent (%) Decrease in Trough Concentration at Steady State (Css, Trough) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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). |
| Measure Participants | 7 | 13 | 9 |
| Total GDC-0449 |
0
0%
|
1
4.5%
|
4
18.2%
|
| Unbound GDC-0449 |
0
0%
|
6
27.3%
|
9
40.9%
|
| Title | Ratio of Total and Unbound Trough GDC-0449 Concentration Between Day 57 to Day 15 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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). |
| Measure Participants | 7 | 13 | 9 |
| Css,trough for Total GDC-0449 |
1.23
|
0.87
|
0.54
|
| Css,trough for Unbound GDC-0449 |
1.34
|
0.58
|
0.20
|
| Title | Plasma Concentration at Steady State (Css) for Total and Unbound GDC-0449 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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). |
| Measure Participants | 15 | 18 | 18 |
| 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)
|
| Title | Maximum Plasma Concentration (Cmax) of Total and Unbound GDC-0449 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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). |
| Measure Participants | 20 | 21 | 22 |
| 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)
|
| Title | Area Under the Curve From Time Zero to 24 Hour (AUC0-24) for Total and Unbound GDC-0449 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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). |
| Measure Participants | 20 | 21 | 22 |
| 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)
|
| Title | Area Under the Curve From Time Zero to the Last Measured Concentration (AUClast) for Total and Unbound GDC-0449 |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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). |
| Measure Participants | 20 | 21 | 22 |
| 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)
|
| Title | Duration of Response (DR) |
|---|---|
| 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
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time to Achieve Maximum Observed Plasma Concentration (Tmax) After a Single Dose of GDC-0449 |
|---|---|
| Description | |
| Time Frame | 0, 1, 2, 4, 6, 24, 48, 72 hours on Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Evaluable Population. |
| Arm/Group Title | GDC-0449 150 mg: All Participants |
|---|---|
| Arm/Group Description | All participants received single dose of GDC-0449 150 mg capsule orally on Day 1. |
| Measure Participants | 63 |
| Total GDC-0449 |
48
|
| Unbound GDC-0449 |
48
|
Adverse Events
| 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 | |||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| GDC-0449 150 mg QD | GDC-0449 150 mg TIW | GDC-0449 150 mg QW | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/20 (30%) | 8/21 (38.1%) | 8/22 (36.4%) | |||
| Gastrointestinal disorders | ||||||
| Intestinal obstruction | 3/20 (15%) | 0/21 (0%) | 0/22 (0%) | |||
| Small intestinal obstruction | 1/20 (5%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Abdominal pain upper | 0/20 (0%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Constipation | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Jejunal ulcer | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Ileus paralytic | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Gastrointestinal haemorrhage | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Upper gastrointestinal haemorrhage | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| General disorders | ||||||
| Gait disturbance | 0/20 (0%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Pain | 0/20 (0%) | 1/21 (4.8%) | 0/22 (0%) | |||
| Infections and infestations | ||||||
| Urosepsis | 0/20 (0%) | 2/21 (9.5%) | 0/22 (0%) | |||
| Abdominal wall abscess | 0/20 (0%) | 1/21 (4.8%) | 0/22 (0%) | |||
| Pneumonia | 0/20 (0%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Cystitis | 0/20 (0%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Injury, poisoning and procedural complications | ||||||
| Thoracic vertebral fracture | 0/20 (0%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Metabolism and nutrition disorders | ||||||
| Dehydration | 1/20 (5%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 0/20 (0%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Nervous system disorders | ||||||
| Headache | 0/20 (0%) | 1/21 (4.8%) | 0/22 (0%) | |||
| Spinal cord compression | 0/20 (0%) | 1/21 (4.8%) | 0/22 (0%) | |||
| Psychiatric disorders | ||||||
| Mental status changes | 0/20 (0%) | 1/21 (4.8%) | 0/22 (0%) | |||
| Renal and urinary disorders | ||||||
| Renal failure acute | 0/20 (0%) | 1/21 (4.8%) | 0/22 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Chronic obstructive pulmonary disease | 0/20 (0%) | 1/21 (4.8%) | 0/22 (0%) | |||
| Vascular disorders | ||||||
| Lymphoedema | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| GDC-0449 150 mg QD | GDC-0449 150 mg TIW | GDC-0449 150 mg QW | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 19/20 (95%) | 19/21 (90.5%) | 20/22 (90.9%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 4/20 (20%) | 4/21 (19%) | 2/22 (9.1%) | |||
| Thrombocytopenia | 0/20 (0%) | 2/21 (9.5%) | 1/22 (4.5%) | |||
| Iron deficiency anaemia | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Paratracheal lymphadenopathy | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Cardiac disorders | ||||||
| Tachycardia | 1/20 (5%) | 2/21 (9.5%) | 1/22 (4.5%) | |||
| Sinus bradycardia | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Ear and labyrinth disorders | ||||||
| Ear congestion | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Endocrine disorders | ||||||
| Adrenal insufficiency | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Eye disorders | ||||||
| Conjunctivitis | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Photopsia | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Visual impairment | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Gastrointestinal disorders | ||||||
| Nausea | 11/20 (55%) | 8/21 (38.1%) | 8/22 (36.4%) | |||
| Vomiting | 7/20 (35%) | 3/21 (14.3%) | 8/22 (36.4%) | |||
| Abdominal pain | 3/20 (15%) | 4/21 (19%) | 6/22 (27.3%) | |||
| Abdominal pain upper | 3/20 (15%) | 3/21 (14.3%) | 5/22 (22.7%) | |||
| Constipation | 4/20 (20%) | 2/21 (9.5%) | 4/22 (18.2%) | |||
| Diarrhoea | 4/20 (20%) | 1/21 (4.8%) | 2/22 (9.1%) | |||
| Dysphagia | 3/20 (15%) | 1/21 (4.8%) | 1/22 (4.5%) | |||
| Abdominal discomfort | 1/20 (5%) | 1/21 (4.8%) | 2/22 (9.1%) | |||
| Abdominal distension | 2/20 (10%) | 1/21 (4.8%) | 1/22 (4.5%) | |||
| Ascites | 3/20 (15%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Abdominal pain lower | 2/20 (10%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Dry mouth | 0/20 (0%) | 0/21 (0%) | 3/22 (13.6%) | |||
| Dyspepsia | 1/20 (5%) | 1/21 (4.8%) | 1/22 (4.5%) | |||
| Flatulence | 1/20 (5%) | 1/21 (4.8%) | 1/22 (4.5%) | |||
| Faeces hard | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Gastrooesophageal reflux disease | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Hypoaesthesia oral | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Rectal haemorrhage | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Stomatitis | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Tongue ulceration | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| General disorders | ||||||
| Fatigue | 8/20 (40%) | 8/21 (38.1%) | 9/22 (40.9%) | |||
| Oedema peripheral | 3/20 (15%) | 2/21 (9.5%) | 3/22 (13.6%) | |||
| Pain | 1/20 (5%) | 3/21 (14.3%) | 1/22 (4.5%) | |||
| Early satiety | 4/20 (20%) | 0/21 (0%) | 0/22 (0%) | |||
| Chest pain | 0/20 (0%) | 2/21 (9.5%) | 1/22 (4.5%) | |||
| Chills | 0/20 (0%) | 2/21 (9.5%) | 1/22 (4.5%) | |||
| Pyrexia | 1/20 (5%) | 0/21 (0%) | 2/22 (9.1%) | |||
| Asthenia | 1/20 (5%) | 1/21 (4.8%) | 0/22 (0%) | |||
| Catheter site pain | 1/20 (5%) | 1/21 (4.8%) | 0/22 (0%) | |||
| Gait disturbance | 1/20 (5%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Oedema | 2/20 (10%) | 0/21 (0%) | 0/22 (0%) | |||
| Suprapubic pain | 1/20 (5%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Mucosal inflammation | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Non-cardiac chest pain | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Swelling | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Hepatobiliary disorders | ||||||
| Jaundice | 0/20 (0%) | 2/21 (9.5%) | 0/22 (0%) | |||
| Infections and infestations | ||||||
| Urinary tract infection | 0/20 (0%) | 3/21 (14.3%) | 2/22 (9.1%) | |||
| Candidiasis | 1/20 (5%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Infection | 0/20 (0%) | 2/21 (9.5%) | 0/22 (0%) | |||
| Oral herpes | 0/20 (0%) | 0/21 (0%) | 2/22 (9.1%) | |||
| Pneumonia | 0/20 (0%) | 0/21 (0%) | 2/22 (9.1%) | |||
| Herpes zoster | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Skin candida | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Fall | 0/20 (0%) | 2/21 (9.5%) | 3/22 (13.6%) | |||
| Drug toxicity | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Investigations | ||||||
| Weight decreased | 4/20 (20%) | 4/21 (19%) | 5/22 (22.7%) | |||
| Blood alkaline phosphatase increased | 1/20 (5%) | 5/21 (23.8%) | 2/22 (9.1%) | |||
| Aspartate aminotransferase increased | 0/20 (0%) | 4/21 (19%) | 2/22 (9.1%) | |||
| Blood lactate dehydrogenase increased | 0/20 (0%) | 2/21 (9.5%) | 3/22 (13.6%) | |||
| Alanine aminotransferase increased | 0/20 (0%) | 1/21 (4.8%) | 2/22 (9.1%) | |||
| Blood creatinine increased | 1/20 (5%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Blood chloride decreased | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Body temperature increased | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Breath sounds abnormal | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| White blood cell count increased | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 6/20 (30%) | 6/21 (28.6%) | 5/22 (22.7%) | |||
| Dehydration | 3/20 (15%) | 3/21 (14.3%) | 4/22 (18.2%) | |||
| Hypokalaemia | 1/20 (5%) | 2/21 (9.5%) | 0/22 (0%) | |||
| Hypercalcaemia | 1/20 (5%) | 1/21 (4.8%) | 0/22 (0%) | |||
| Hyperglycaemia | 1/20 (5%) | 1/21 (4.8%) | 0/22 (0%) | |||
| Hypoalbuminaemia | 1/20 (5%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Hyponatraemia | 1/20 (5%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Hypocalcaemia | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Muscle spasms | 6/20 (30%) | 3/21 (14.3%) | 5/22 (22.7%) | |||
| Back pain | 3/20 (15%) | 2/21 (9.5%) | 4/22 (18.2%) | |||
| Musculoskeletal chest pain | 4/20 (20%) | 1/21 (4.8%) | 3/22 (13.6%) | |||
| Musculoskeletal pain | 1/20 (5%) | 2/21 (9.5%) | 2/22 (9.1%) | |||
| Myalgia | 0/20 (0%) | 1/21 (4.8%) | 4/22 (18.2%) | |||
| Arthralgia | 2/20 (10%) | 2/21 (9.5%) | 0/22 (0%) | |||
| Neck pain | 1/20 (5%) | 1/21 (4.8%) | 2/22 (9.1%) | |||
| Muscular weakness | 1/20 (5%) | 1/21 (4.8%) | 0/22 (0%) | |||
| Pain in extremity | 1/20 (5%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Musculoskeletal stiffness | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Tumour associated fever | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Nervous system disorders | ||||||
| Dizziness | 3/20 (15%) | 2/21 (9.5%) | 3/22 (13.6%) | |||
| Headache | 1/20 (5%) | 3/21 (14.3%) | 3/22 (13.6%) | |||
| Dysgeusia | 2/20 (10%) | 4/21 (19%) | 0/22 (0%) | |||
| Hypogeusia | 2/20 (10%) | 0/21 (0%) | 0/22 (0%) | |||
| Sinus headache | 0/20 (0%) | 0/21 (0%) | 2/22 (9.1%) | |||
| Hypoaesthesia | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Neuropathy peripheral | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Poor quality sleep | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Psychiatric disorders | ||||||
| Depression | 1/20 (5%) | 2/21 (9.5%) | 1/22 (4.5%) | |||
| Insomnia | 0/20 (0%) | 1/21 (4.8%) | 3/22 (13.6%) | |||
| Anxiety | 1/20 (5%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Confusional state | 0/20 (0%) | 2/21 (9.5%) | 0/22 (0%) | |||
| Renal and urinary disorders | ||||||
| Dysuria | 1/20 (5%) | 1/21 (4.8%) | 1/22 (4.5%) | |||
| Chromaturia | 0/20 (0%) | 2/21 (9.5%) | 0/22 (0%) | |||
| Haematuria | 1/20 (5%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Urinary retention | 1/20 (5%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 4/20 (20%) | 5/21 (23.8%) | 4/22 (18.2%) | |||
| Dyspnoea | 1/20 (5%) | 6/21 (28.6%) | 4/22 (18.2%) | |||
| Hypoxia | 1/20 (5%) | 1/21 (4.8%) | 2/22 (9.1%) | |||
| Dyspnoea exertional | 3/20 (15%) | 0/21 (0%) | 0/22 (0%) | |||
| Oropharyngeal pain | 1/20 (5%) | 1/21 (4.8%) | 1/22 (4.5%) | |||
| Tachypnoea | 1/20 (5%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Atelectasis | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Hiccups | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Upper-airway cough syndrome | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Pruritus | 2/20 (10%) | 1/21 (4.8%) | 0/22 (0%) | |||
| Rash | 1/20 (5%) | 1/21 (4.8%) | 1/22 (4.5%) | |||
| Decubitus ulcer | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Petechiae | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Skin lesion | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Subcutaneous nodule | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Vascular disorders | ||||||
| Hypotension | 2/20 (10%) | 1/21 (4.8%) | 0/22 (0%) | |||
| Hypertension | 1/20 (5%) | 0/21 (0%) | 1/22 (4.5%) | |||
| Deep vein thrombosis | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
| Lymphoedema | 1/20 (5%) | 0/21 (0%) | 0/22 (0%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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 |
| genentech@druginfo.com |
Responsible Party:
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT00968981
Other Study ID Numbers:
- SHH4610g
First Posted:
Aug 31, 2009
Last Update Posted:
Jul 11, 2017
Last Verified:
Jun 1, 2017