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Trial record 24 of 78 for:    vismodegib

A Study Evaluating the Efficacy and Safety of Vismodegib (GDC-0449, Hedgehog Pathway Inhibitor) in Patients With Advanced Basal Cell Carcinoma

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ClinicalTrials.gov Identifier: NCT00833417
Recruitment Status : Completed
First Posted : February 2, 2009
Results First Posted : April 30, 2012
Last Update Posted : May 20, 2015
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Basal Cell Carcinoma
Intervention Drug: Vismodegib 150 mg
Enrollment 104
Recruitment Details The study population consisted of patients ≥ 18 years old with a histologically confirmed diagnosis of advanced basal cell carcinoma (BCC), either metastatic or locally advanced BCC. Enrollment of patients with locally advanced BCC was limited to 80 of a planned total of 100 patients. Both cohorts received the same vismodegib 150 mg treatment.
Pre-assignment Details  
Arm/Group Title Metastatic BCC Cohort Locally Advanced BCC Cohort
Hide Arm/Group Description Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study. Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study.
Period Title: Overall Study
Started 33 71
Completed 0 0
Not Completed 33 71
Reason Not Completed
Adverse Event             5             16
Death             1             3
Lost to Follow-up             1             2
Physician Decision to Withdraw Patient             3             7
Patient Decision to Withdraw             4             23
Sponsor Decision to Terminate Study             1             2
Disease Progression             18             17
Reason Not Specified             0             1
Arm/Group Title Metastatic BCC Cohort Locally Advanced BCC Cohort Total
Hide Arm/Group Description Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study. Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study. Total of all reporting groups
Overall Number of Baseline Participants 33 71 104
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 33 participants 71 participants 104 participants
61.6  (11.4) 61.2  (16.8) 61.4  (15.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 71 participants 104 participants
Female
9
  27.3%
32
  45.1%
41
  39.4%
Male
24
  72.7%
39
  54.9%
63
  60.6%
1.Primary Outcome
Title Objective Response (OR) Determined by the Independent Review Facility
Hide Description OR=complete (CR) or partial response (PR). Metastatic-CR:Disappearance of all targets. PR:≥30% decreased sum of longest diameter (SLD) of targets compared to baseline (B). Locally advanced-Response=No progressive disease (PD) and ≥30% decreased SLD from baseline (radiography [R]) or ≥30% decreased SLD from B (externally visible dimension [EVD]) or completely resolved ulceration. CR:Response with no residual BCC on tumor biopsy (otherwise response was PR). PD:Any of ≥20% increased SLD from nadir (R or EVD), new ulceration, new lesions (R or physical exam) or non-target lesion progression by R.
Time Frame From study initiation (enrollment of first patient) through 9 months following the first treatment of the last enrolled patient (clinical cutoff date of 26 November 2010), up to 90 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy-evaluable population: All treated patients for whom the independent pathologist’s interpretation of archival tissue or baseline biopsies was consistent with basal cell carcinoma.
Arm/Group Title Metastatic BCC Cohort Locally Advanced BCC Cohort
Hide Arm/Group Description:
Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study.
Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study.
Overall Number of Participants Analyzed 33 63
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
30.3
(15.6 to 48.2)
42.9
(30.5 to 56.0)
2.Secondary Outcome
Title Duration of Objective Response (OR) Determined by the Independent Review Facility
Hide Description Duration of OR was defined as the time from the initial CR or PR to the earliest documented disease progression (PD) or death. Metastatic BCC - PD: ≥ 20% increased sum of the longest diameter (SLD) of targets from nadir, or 1 or more new lesions. Locally advanced BCC - PD: any of: (1) ≥ 20% increased SLD from nadir (radiography or externally visible dimension); (2) new ulceration; (3) new lesions (radiography or physical exam); (4) progression of non-target lesions by radiography.
Time Frame From study initiation (enrollment of first patient) through 9 months following the first treatment of the last enrolled patient (clinical cutoff date of 26 November 2010), up to 90 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy-evaluable population: All treated patients for whom the independent pathologist’s interpretation of archival tissue or baseline biopsies was consistent with basal cell carcinoma.
Arm/Group Title Metastatic BCC Cohort Locally Advanced BCC Cohort
Hide Arm/Group Description:
Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study.
Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study.
Overall Number of Participants Analyzed 10 27
Median (95% Confidence Interval)
Unit of Measure: Months
7.6 [1] 
(5.62 to NA)
7.6
(5.65 to 9.66)
[1]
The upper limit of the 95% confidence interval could not be estimated due to the small number of patients who had an objective response.
3.Secondary Outcome
Title Progression-free Survival (PFS) Determined by the Independent Review Facility
Hide Description PFS was defined as the time from start of treatment to the earliest documented disease progression (PD) or death. Metastatic BCC - PD: ≥ 20% increased sum of the longest diameter (SLD) of targets from nadir, or 1 or more new lesions. Locally advanced BCC - PD: any of: (1) ≥ 20% increased SLD from nadir (radiography or externally visible dimension); (2) new ulceration; (3) new lesions (radiography or physical exam); (4) progression of non-target lesions by radiography.
Time Frame From study initiation (enrollment of first patient) through 9 months following the first treatment of the last enrolled patient (clinical cutoff date of 26 November 2010), up to 90 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy-evaluable population: All treated patients for whom the independent pathologist’s interpretation of archival tissue or baseline biopsies was consistent with basal cell carcinoma.
Arm/Group Title Metastatic BCC Cohort Locally Advanced BCC Cohort
Hide Arm/Group Description:
Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study.
Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study.
Overall Number of Participants Analyzed 33 63
Median (95% Confidence Interval)
Unit of Measure: Months
9.5 [1] 
(7.36 to NA)
9.5
(7.39 to 11.93)
[1]
The upper limit of the 95% confidence interval could not be estimated due to the small number of patients with disease progression.
4.Secondary Outcome
Title Overall Survival
Hide Description Overall survival was defined as the time from the initial dose of vismodegib until death from any cause.
Time Frame From study initiation (enrollment of first patient) through 9 months following the first treatment of the last enrolled patient (clinical cutoff date of 26 November 2010), up to 90 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy-evaluable population: All treated patients for whom the independent pathologist’s interpretation of archival tissue or baseline biopsies was consistent with basal cell carcinoma.
Arm/Group Title Metastatic BCC Cohort Locally Advanced BCC Cohort
Hide Arm/Group Description:
Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study.
Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study.
Overall Number of Participants Analyzed 33 63
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [2] 
(NA to NA)
[1]
The data were not mature for analysis. Only 7 deaths were reported as of the 26 November 2010 data cutoff.
[2]
The data were not mature for analysis. Only 6 deaths were reported as of the 26 November 2010 data cutoff.
5.Secondary Outcome
Title Change From Baseline in Short Form 36 (SF-36) Health Survey Scores
Hide Description The SF-36 Health Survey (Version 2) uses patient-reported symptoms on 8 subscales to assess health-related quality of life (HRQoL). The Physical Component Summary (PCS) score summarizes the subscales Physical Functioning, Role−Physical, Bodily Pain, and General Health. The Mental Component Summary (MCS) score summarizes the subscales Vitality, Social Functioning, Role−Emotional, and Mental Health. Each score was scaled from 0 to 100. A positive change score indicates better HRQoL.
Time Frame Baseline, Week 12, Week 24, and at the end of the study or early termination visit, up to 90 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy-evaluable population: All treated patients for whom the independent pathologist’s interpretation of archival tissue or baseline biopsies was consistent with basal cell carcinoma.
Arm/Group Title Metastatic and Locally Advanced BCC Cohorts
Hide Arm/Group Description:
Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study.
Overall Number of Participants Analyzed 93
Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
Change in MCS score at Week 12, n=82
2.20
(-0.22 to 4.62)
Change in MCS score at Week 24, n=75
2.29
(0.05 to 4.53)
Change in MCS score at end of study, n=20
-3.80
(-10.55 to 2.96)
Change in PCS score at Week 12, n=82
-1.25
(-2.86 to 0.36)
Change in PCS score at Week 24, n=75
-1.90
(-3.75 to -0.05)
Change in PCS score at end of study, n=20
-2.86
(-7.39 to 1.66)
6.Secondary Outcome
Title Percentage of Patients With Absence of Residual Basal Cell Carcinoma (BCC) in Patients With Locally Advanced BCC
Hide Description In patients with locally advanced BCC, the histopathological effect of vismodegib was determined in tissue biopsies obtained at baseline and following vismodegib treatment. Reported are the percentage of patients with pathology confirmed BCC in baseline biopsy who had an absence of residual BCC post-baseline as assessed by an independent pathological review.
Time Frame From baseline through end of the study, up to 90 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy-evaluable population: All treated patients for whom the independent pathologist’s interpretation of archival tissue or baseline biopsies was consistent with basal cell carcinoma. Only locally advanced BCC patients with available post-baseline biopsy assessed by an independent pathologist were included in the analysis.
Arm/Group Title Locally Advanced BCC Cohort
Hide Arm/Group Description:
Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study.
Overall Number of Participants Analyzed 51
Measure Type: Number
Unit of Measure: Percentage of participants
Total 54.0
Prior to Week 24 9.5
At Week 24 42.9
After Week 24 1.6
Time Frame Adverse events and serious adverse events were recorded from study initiation (enrollment of first patient) through the end of the study (09 Apr 2014).
Adverse Event Reporting Description Adverse events were reported for the safety analysis population, which was defined as all enrolled patients who received any amount of study drug.
 
Arm/Group Title Metastatic and Locally Advanced BCC Cohorts
Hide Arm/Group Description Patients received vismodegib 150 mg orally once daily until disease progression; intolerable toxicity, most probably attributable to vismodegib; or withdrawal from the study.
All-Cause Mortality
Metastatic and Locally Advanced BCC Cohorts
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Metastatic and Locally Advanced BCC Cohorts
Affected / at Risk (%)
Total   36/104 (34.62%) 
Blood and lymphatic system disorders   
Anaemia  1  1/104 (0.96%) 
Cardiac disorders   
Cardiac failure  1  2/104 (1.92%) 
Acute myocardial infarction  1  1/104 (0.96%) 
Angina pectoris  1  1/104 (0.96%) 
Left ventricular dysfunction  1  1/104 (0.96%) 
Myocardial infarction  1  1/104 (0.96%) 
Restrictive cardiomyopathy  1  1/104 (0.96%) 
Atrial fibrillation  1  1/104 (0.96%) 
Cardiac flutter  1  1/104 (0.96%) 
Eye disorders   
Eye haemorrhage  1  1/104 (0.96%) 
Ulcerative keratitis  1  1/104 (0.96%) 
Gastrointestinal disorders   
Aphagia  1  1/104 (0.96%) 
Small intestinal obstruction  1  1/104 (0.96%) 
Food poisoning  1  1/104 (0.96%) 
Gastrointestinal haemorrhage  1  2/104 (1.92%) 
General disorders   
Death  1  3/104 (2.88%) 
Asthenia  1  1/104 (0.96%) 
Chest discomfort  1  1/104 (0.96%) 
Chest pain  1  1/104 (0.96%) 
General physical health deterioration  1  1/104 (0.96%) 
Pyrexia  1  1/104 (0.96%) 
Hepatobiliary disorders   
Cholestasis  1  1/104 (0.96%) 
Infections and infestations   
Pneumonia  1  4/104 (3.85%) 
Cellulitis  1  2/104 (1.92%) 
Meningitis viral  1  1/104 (0.96%) 
Urinary tract infection  1  1/104 (0.96%) 
Osteomyelitis  1  1/104 (0.96%) 
Sepsis  1  1/104 (0.96%) 
Injury, poisoning and procedural complications   
Cervical vertebral fracture  1  1/104 (0.96%) 
Spinal compression fracture  1  1/104 (0.96%) 
Hip fracture  1  3/104 (2.88%) 
Ankle fracture  1  1/104 (0.96%) 
Overdose  1  1/104 (0.96%) 
Rib fracture  1  1/104 (0.96%) 
Toxicity to various agents  1  1/104 (0.96%) 
Upper limb fracture  1  1/104 (0.96%) 
Metabolism and nutrition disorders   
Dehydration  1  1/104 (0.96%) 
Hypokalaemia  1  1/104 (0.96%) 
Musculoskeletal and connective tissue disorders   
Pain in extremity  1  1/104 (0.96%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Malignant melanoma  1  1/104 (0.96%) 
Metastatic malignant melanoma  1  1/104 (0.96%) 
Metastatic squamous cell carcinoma  1  1/104 (0.96%) 
Oesophageal carcinoma  1  1/104 (0.96%) 
Sarcoma  1  1/104 (0.96%) 
Squamous cell carcinoma  1  2/104 (1.92%) 
Metastases to meninges  1  1/104 (0.96%) 
Nervous system disorders   
Convulsion  1  1/104 (0.96%) 
Ischaemic stroke  1  1/104 (0.96%) 
Syncope  1  4/104 (3.85%) 
Cerebral haemorrhage  1  1/104 (0.96%) 
Epilepsy  1  1/104 (0.96%) 
Transient ischaemic attack  1  1/104 (0.96%) 
Psychiatric disorders   
Depression  1  1/104 (0.96%) 
Suicidal ideation  1  1/104 (0.96%) 
Renal and urinary disorders   
Renal failure  1  1/104 (0.96%) 
Respiratory, thoracic and mediastinal disorders   
Pulmonary embolism  1  2/104 (1.92%) 
Pneumonia aspiration  1  1/104 (0.96%) 
Pneumothorax  1  1/104 (0.96%) 
Vascular disorders   
Deep vein thrombosis  1  2/104 (1.92%) 
Haemorrhage  1  1/104 (0.96%) 
Hypovolaemic shock  1  1/104 (0.96%) 
Orthostatic hypotension  1  1/104 (0.96%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (Unspecified)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Metastatic and Locally Advanced BCC Cohorts
Affected / at Risk (%)
Total   103/104 (99.04%) 
Blood and lymphatic system disorders   
Anaemia  1  8/104 (7.69%) 
Gastrointestinal disorders   
Nausea  1  34/104 (32.69%) 
Diarrhoea  1  28/104 (26.92%) 
Constipation  1  20/104 (19.23%) 
Vomiting  1  19/104 (18.27%) 
Dyspepsia  1  11/104 (10.58%) 
Flatulence  1  6/104 (5.77%) 
Abdominal pain  1  7/104 (6.73%) 
General disorders   
Fatigue  1  45/104 (43.27%) 
Asthenia  1  10/104 (9.62%) 
Pain  1  10/104 (9.62%) 
Influenza like illness  1  7/104 (6.73%) 
Infections and infestations   
Nasopharyngitis  1  14/104 (13.46%) 
Upper respiratory tract infection  1  9/104 (8.65%) 
Urinary tract infection  1  10/104 (9.62%) 
Sinusitis  1  7/104 (6.73%) 
Injury, poisoning and procedural complications   
Procedural pain  1  7/104 (6.73%) 
Investigations   
Weight decreased  1  54/104 (51.92%) 
Metabolism and nutrition disorders   
Decreased appetite  1  29/104 (27.88%) 
Musculoskeletal and connective tissue disorders   
Muscle spasms  1  75/104 (72.12%) 
Arthralgia  1  15/104 (14.42%) 
Pain in extremity  1  7/104 (6.73%) 
Back pain  1  6/104 (5.77%) 
Myalgia  1  7/104 (6.73%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Squamous cell carcinoma  1  12/104 (11.54%) 
Nervous system disorders   
Dysgeusia  1  58/104 (55.77%) 
Headache  1  16/104 (15.38%) 
Ageusia  1  12/104 (11.54%) 
Hypogeusia  1  11/104 (10.58%) 
Paraesthesia  1  7/104 (6.73%) 
Dizziness  1  7/104 (6.73%) 
Psychiatric disorders   
Depression  1  7/104 (6.73%) 
Anxiety  1  6/104 (5.77%) 
Insomnia  1  7/104 (6.73%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  21/104 (20.19%) 
Dyspnoea  1  8/104 (7.69%) 
Rhinorrhoea  1  7/104 (6.73%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  69/104 (66.35%) 
Pruritus  1  11/104 (10.58%) 
Hair growth abnormal  1  6/104 (5.77%) 
Rash  1  8/104 (7.69%) 
Actinic keratosis  1  6/104 (5.77%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (Unspecified)
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: Genentech, Inc.
Phone: 800-821-8590
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00833417     History of Changes
Other Study ID Numbers: SHH4476g
GO01541
First Submitted: January 30, 2009
First Posted: February 2, 2009
Results First Submitted: February 23, 2012
Results First Posted: April 30, 2012
Last Update Posted: May 20, 2015