Status and phase
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About
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.
Full description
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).
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Men with metastatic castration-resistant prostate cancer (mCRPC), with accessible metastatic soft-tissue lesions for tumor biopsy
Greater than 18 years of age
Evidence of disease progression (PSA progression, or radiographic/clinical progression [PCWG2])
Presence of ≥1 metastatic site (nodal, visceral) that is amenable to core biopsy
Castrate serum testosterone (<50 ng/dL)
Prior anti-androgens are permitted but not required (2 week washout from anti-androgens)
Prior abiraterone and enzalutamide are permitted (2 week washout for both agents)
Prior immunotherapy (e.g. sipuleucel-T), and chemotherapy are permitted (4 week washout period from chemotherapy)
Bisphosphonates and denosumab are permitted, if on a stable dose for ≥4 weeks
Life expectancy ≥12 months
Adequate renal, liver, and bone marrow function with the following acceptable initial laboratory values:
Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information.
NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
9 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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