Ignite Creation Date:
2024-05-06 @ 12:28 PM
Last Modification Date:
2024-10-26 @ 12:59 PM
Study NCT ID:
NCT03767439
Status:
WITHDRAWN
Last Update Posted:
2019-12-18
First Post:
2018-12-05
Brief Title:
Nivolumab With Vismodegib in Patients With Basal Cell Nevus Syndrome
Sponsor:
Columbia University
Organization:
Columbia University
Study Overview
Official Title:
Trial of Nivolumab With Vismodegib in Patients With Basal Cell Nevus Syndrome BCNS
Status:
WITHDRAWN
Status Verified Date:
2019-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Loss of funding
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a single-arm phase II study to assess the efficacy of combined SMO and PD-1 inhibition with Vismodegib SMO inhibitor and Nivolumab anti-PD-1 antibody in BCNS patients target enrollment of 22 patients with a primary endpoint of 18-month disease control rate The purpose of this study is to test the hypothesis that Nivolumab and Vismodegib will improve the percentage of BCNS patients who achieve disease control defined as total tumor burden 50 of baseline at 18 months from 50 to 80 Baseline and on-treatment biopsies will be obtained to characterize the immune effects of combined SMO and PD-1 inhibition
Detailed Description:
Basal cell carcinoma BCC is by far the most common form of human malignancy affecting more than 35 million Americans each year Aberrant activation of the Hedgehog Hh pathway typically through loss of the receptor Patched PTCH or oncogenic activation of Smoothened SMO has been identified as the primary driver of BCC growth and development In particular up to 1 in 57000 individuals in the US are affected by a rare autosomal dominant disorder characterized by mutations in protein patched homolog 1 PTCH1 known as basal cell nevus syndrome BCNS These patients can develop dozens to hundreds of BCCs at any one time 1-5 Surgical removal of the entire tumor burden is not feasible
Hh-targeted therapies employing inhibitors of SMO ie Vismodegib Sonidegib have shown remarkable efficacy in reducing tumor burden in BCC patients However the sustained clinical utility of these agents has been hampered by the rapid development of clinical resistance significant tumor recurrence and toxicity Treatment strategies directed at finding additional molecular or immunological targets may enhance the possibility of sustained remission andor cure of these tumors Emerging data from our research group and others suggest the therapeutic efficacy of SMO inhibition may be dependent on immunological mechanisms Hh inhibition appears to increase T cell recruitment and activation as well as upregulate major histocompatibility complex MHC class I expression on tumor cells These data together with case reports demonstrating the efficacy of cytotoxic T-lymphocyte associated protein 4 CTLA-4 and programmed death-1 PD-1 inhibition in Hh inhibitor-naïve and resistant BCCs support a role for anti-tumor immunity in BCC and underscore the potential enhanced therapeutic efficacy of combined SMO and immunological checkpoint inhibition
Hh-targeted therapies employing inhibitors of SMO ie Vismodegib Sonidegib have shown remarkable efficacy in reducing tumor burden in BCC patients However the sustained clinical utility of these agents has been hampered by the rapid development of clinical resistance significant tumor recurrence and toxicity Treatment strategies directed at finding additional molecular or immunological targets may enhance the possibility of sustained remission andor cure of these tumors Emerging data from our research group and others suggest the therapeutic efficacy of SMO inhibition may be dependent on immunological mechanisms Hh inhibition appears to increase T cell recruitment and activation as well as upregulate major histocompatibility complex MHC class I expression on tumor cells These data together with case reports demonstrating the efficacy of cytotoxic T-lymphocyte associated protein 4 CTLA-4 and programmed death-1 PD-1 inhibition in Hh inhibitor-naïve and resistant BCCs support a role for anti-tumor immunity in BCC and underscore the potential enhanced therapeutic efficacy of combined SMO and immunological checkpoint inhibition
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None