A Study of Vismodegib in Men With Metastatic CRPC With Accessible Metastatic Lesions for Tumor Biopsy
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02115828|
Recruitment Status : Completed
First Posted : April 16, 2014
Results First Posted : July 20, 2018
Last Update Posted : July 20, 2018
This is a single-arm pharmacodynamic study with mandatory metastatic tumor biopsies in men with castration-resistant prostate cancer.
The trial will evaluate the effect of vismodegib on tumor tissue in men with metastatic CRPC by obtaining tumor biopsies at baseline and after 4 weeks of treatment with vismodegib.
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Drug: Vismodegib||Early Phase 1|
The study will enroll 10 evaluable patients. Patients will receive a 30-day supply of 150 mg of vismodegib on day one of each cycle daily by mouth, beginning on Day 1, and continuously until one of the following occurs: Disease progression, intolerable toxicity most probably attributable to vismodegib or withdrawal from the study.
Tumor biopsies (nodal or visceral), skin biopsies, and CTCs will be obtained at baseline and after 4 weeks of treatment. PSA evaluations will be conducted every 4 weeks, imaging assessments (CT and Bone scan) will be conducted every 12 weeks and routine labs (blood counts and chemistry panel) will be conducted every 4 weeks.
The investigator's intent is to examine the fold change in GLI1 expression in each man following exposure to drug (comparing pre-treatment and on-treatment core biopsy samples). As secondary endpoints, the investigator will also explore clinical response (PSA responses, progression-free survival [PFS], radiographic responses), safety, and will examine changes from baseline in Gli2, PTCH1, and AKT1 mRNA levels by qRT-PCR, in situ GLI1 expression in tissue sections by mRNA in situ hybridization, and GLI1 expression in isolated circulating tumor cells (CTCs).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||9 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pharmacodynamic Study of Vismodegib in Men With Metastatic Castration-resistant Prostate Cancer (mCRPC) With Accessible Metastatic Lesions for Tumor Biopsy|
|Study Start Date :||April 2014|
|Actual Primary Completion Date :||April 2016|
|Actual Study Completion Date :||April 2016|
Vismodegib Treatment arm will receive Vismodegib by mouth 150 mg daily up to 1 year.
- The Proportion of mCRPC Patients Treated With Vismodegib Who Achieve a Pharmacodynamic (PD) Response in Tumor Biopsies [ Time Frame: Up to 1 year ]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.
- GLI1 Expression [ Time Frame: Up to 1 Year ]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.
- Progression-free Survival (PFS) [ Time Frame: Up to 1 Year ]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.
- AKT1 Expression in Tumor Biopsies [ Time Frame: Up to 1 Year ]The tumor biopsies were evaluated for changes to Hh-regulated transcript, AKT1, between pre-treatment and post-treatment
- The Effect of Vismodegib on PSA Responses [ Time Frame: Up to 1 Year ]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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02115828
|United States, Maryland|
|Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21205|
|Principal Investigator:||Emmanuel Antonarakis, M.D.||Johns Hopkins University|