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Trial record 6 of 78 for:    vismodegib

A Study of Vismodegib in Men With Metastatic CRPC With Accessible Metastatic Lesions for Tumor Biopsy

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ClinicalTrials.gov Identifier: NCT02115828
Recruitment Status : Completed
First Posted : April 16, 2014
Results First Posted : July 20, 2018
Last Update Posted : July 20, 2018
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Prostate Cancer
Intervention Drug: Vismodegib
Enrollment 9
Recruitment Details A total of 9 patients were enrolled on the study
Pre-assignment Details  
Arm/Group Title Vismodegib
Hide Arm/Group Description

Vismodegib Treatment arm will receive Vismodegib by mouth 150 mg daily up to 1 year.

Vismodegib

Period Title: Overall Study
Started 9
Completed 9
Not Completed 0
Arm/Group Title Vismodegib
Hide Arm/Group Description

Vismodegib Treatment arm will receive Vismodegib by mouth 150 mg daily up to 1 year.

Vismodegib

Overall Number of Baseline Participants 9
Hide Baseline Analysis Population Description
All patients were required to have biopsies of the tumor and skin (a surrogate tissue) at baseline and after 4 weeks of therapy. 9 patients were enrolled. A nuclear medicine bone scan and CT scan of the C/A/P were performed to establish a baseline of the metastatic disease burden.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
<=18 years
0
   0.0%
Between 18 and 65 years
9
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 9 participants
65
(58 to 79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
Female
0
   0.0%
Male
9
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 9 participants
9
1.Primary Outcome
Title The Proportion of mCRPC Patients Treated With Vismodegib Who Achieve a Pharmacodynamic (PD) Response in Tumor Biopsies
Hide Description The primary endpoint is the proportion of mCRPC patients treated with vismodegib who achieve a pharmacodynamic (PD) response in tumor biopsies, defined as both a decrease in GLI1 mRNA greater than 1.2 times the standard deviation (SD) of the baseline values and a ≥50% (≥2-fold) reduction in GLI1 messenger ribonucleic acid (mRNA) expression in metastatic tumor biopsies after 4 weeks of treatment when comparing post-treatment biopsy to pre-treatment biopsy in the same patient.
Time Frame Up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The design had 90% power to detect a true 65% PD response rate across patients, with a false-positive rate of 3.3% under the null hypothesis that vismodegib has no effect in downregulating Gli1 expression.
Arm/Group Title Vismodegib
Hide Arm/Group Description:

Vismodegib Treatment arm will receive Vismodegib by mouth 150 mg daily up to 1 year.

Vismodegib

Overall Number of Participants Analyzed 9
Measure Type: Count of Participants
Unit of Measure: Participants
7
  77.8%
2.Secondary Outcome
Title GLI1 Expression
Hide Description Suppression by vismodegib in tumor tissue of Hh-regulated transcripts and proteins was defined as the change from baseline in expression levels of GLI1 in situ tissue expression by mRNA in situ hybridization.
Time Frame Up to 1 Year
Hide Outcome Measure Data
Hide Analysis Population Description
One patient did not receive a post-treatment biopsy, and another patient had insufficient tissue for evaluation from the repeat biopsy
Arm/Group Title Vismodegib
Hide Arm/Group Description:

Vismodegib Treatment arm will receive Vismodegib by mouth 150 mg daily up to 1 year.

Vismodegib

Overall Number of Participants Analyzed 7
Median (Full Range)
Unit of Measure: expression fold change
-9.8
(-8841 to 122)
3.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description Progression-free survival (PFS) is defined by the Prostate Cancer Working Group 2 (PCWG2) criteria using RECIST 1.1 criteria for each patient. PFS is defined as the time of first dose (a) until prostate specific antigen (PSA) progression (by 25% increase in PSA from nadir) or death and (b) until any evidence of progression (by 25% increase in PSA from nadir, a new lesion on bone or CT scan, or physical examination) or death. PFS will be assigned to the earliest observed time.
Time Frame Up to 1 Year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vismodegib
Hide Arm/Group Description:

Vismodegib Treatment arm will receive Vismodegib by mouth 150 mg daily up to 1 year.

Vismodegib

Overall Number of Participants Analyzed 9
Median (95% Confidence Interval)
Unit of Measure: months
1.9
(1.3 to 1.9)
4.Secondary Outcome
Title AKT1 Expression in Tumor Biopsies
Hide Description The tumor biopsies were evaluated for changes to Hh-regulated transcript, AKT1, between pre-treatment and post-treatment
Time Frame Up to 1 Year
Hide Outcome Measure Data
Hide Analysis Population Description
One patient did not receive a post-treatment biopsy, and another patient had insufficient tissue for evaluation from the repeat biopsy
Arm/Group Title Vismodegib
Hide Arm/Group Description:

Vismodegib Treatment arm will receive Vismodegib by mouth 150 mg daily up to 1 year.

Vismodegib

Overall Number of Participants Analyzed 7
Median (Full Range)
Unit of Measure: expression fold change
-1.15
(-5.28 to 2.93)
5.Secondary Outcome
Title The Effect of Vismodegib on PSA Responses
Hide Description The effect of vismodegib on PSA responses will be assessed as the number of patients with participants with ≥50% PSA reductions at any time point during study
Time Frame Up to 1 Year
Hide Outcome Measure Data
Hide Analysis Population Description
Seven patients were evaluable for PSA response. One participant had no measurable PSA production at enrollment, and PSA remained <0.01 throughout the study. A second patient had disease progression prior to the first on-study PSA evaluation.
Arm/Group Title Vismodegib
Hide Arm/Group Description:

Vismodegib Treatment arm will receive Vismodegib by mouth 150 mg daily up to 1 year.

Vismodegib

Overall Number of Participants Analyzed 7
Measure Type: Number
Unit of Measure: participants
1
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Vismodegib
Hide Arm/Group Description

Vismodegib Treatment arm will receive Vismodegib by mouth 150 mg daily up to 1 year.

Vismodegib

All-Cause Mortality
Vismodegib
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Vismodegib
Affected / at Risk (%) # Events
Total   5/9 (55.56%)    
Cardiac disorders   
chest pain and shortness of breath  [1]  1/9 (11.11%)  1
Gastrointestinal disorders   
Nausea [2]  1/9 (11.11%)  1
vomiting [3]  1/9 (11.11%)  1
General disorders   
Pain grade 3 [4]  1/9 (11.11%)  1
Hepatobiliary disorders   
observation post-TACE [5]  1/9 (11.11%)  1
Metabolism and nutrition disorders   
Dehydration [6]  1/9 (11.11%)  1
Respiratory, thoracic and mediastinal disorders   
Pneumonia [7]  1/9 (11.11%)  1
Indicates events were collected by systematic assessment
[1]
This is a 65 yr old man with Prostate CA , admitted for chest pain and shortness of breath. A cardiac event was ruled out. The cause of his symptoms appeared to be related to his metastatic prostate cancer process.
[2]
Patient was admitted for grade 3 nausea, the SAE was possibly related to the study drug
[3]
Patient was admitted for grade 3 vomiting, this SAE was possibly related to the study drug.
[4]
patient was admitted om 07/15/2015 for pain control issues, SAE was not related to the study drug
[5]
60 year old man with prostate cancer underwent TACE to his liver metastases and and was admitted to the hospital for one night for observation post-TACE. This hospitalization was NOT RELATED to the study drug, vismodegib
[6]
Patient was admitted for grade 3 dehydration, the SAE was possibly related to the study drug
[7]
patient was admitted for grade 3 pneumonia. the SAE was not related to the study drug
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Vismodegib
Affected / at Risk (%) # Events
Total   9/9 (100.00%)    
Gastrointestinal disorders   
nausea  6/9 (66.67%)  6
vomiting  4/9 (44.44%)  4
General disorders   
fatigue  6/9 (66.67%)  9
Metabolism and nutrition disorders   
anorexia  3/9 (33.33%)  5
Musculoskeletal and connective tissue disorders   
musculoskeletal pain  6/9 (66.67%)  12
Nervous system disorders   
dysgeusia  3/9 (33.33%)  4
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Emmanuel Antonarakis, MD
Organization: Johns Hopkins University
Phone: 410-502-7528
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT02115828     History of Changes
Other Study ID Numbers: J1423
NA_00093427 ( Other Identifier: JHMI-IRB )
First Submitted: April 14, 2014
First Posted: April 16, 2014
Results First Submitted: January 11, 2017
Results First Posted: July 20, 2018
Last Update Posted: July 20, 2018