Nivolumab With Vismodegib in Patients With Basal Cell Nevus Syndrome
|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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03767439|
Recruitment Status : Not yet recruiting
First Posted : December 6, 2018
Last Update Posted : April 8, 2019
|Condition or disease||Intervention/treatment||Phase|
|Basal Cell Nevus Syndrome||Drug: Vismodegib Drug: Nivolumab Drug: Ipilimumab||Phase 2|
Basal cell carcinoma (BCC) is by far the most common form of human malignancy, affecting more than 3.5 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 57,000 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 (i.e., 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 and/or 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Trial of Nivolumab With Vismodegib in Patients With Basal Cell Nevus Syndrome (BCNS)|
|Estimated Study Start Date :||June 2019|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||February 2020|
Experimental: Nivolumab, Vismodegib, Ipilimumab
Patients will receive a two week run-in of Vismodegib 150 mg PO daily followed by concurrent Nivolumab 480 mg IV every 4 weeks and Vismodegib 150 mg PO daily.
In an exploratory fashion, patients will have the option to receive combination Ipilimumab 1 mg/kg IV every 6 weeks and Nivolumab 360 mg IV every 3 weeks at the time of disease progression.
150 mg PO daily
Other Name: ERIVEDGE
480 mg IV every 4 weeks
Other Name: OPDIVO
1 mg/kg IV every 6 weeks
Other Name: YERVOY
- Disease control rate [ Time Frame: 18 months ]Defined as the percentage of patients achieving a total tumor burden <50% of baseline tumor burden
- Total Number of Adverse Reactions [ Time Frame: 18 months ]Testing safety and toxicity assessed using CTCAE v5.0 criteria
- Disease Control Rate (DCR) [ Time Frame: 18 months ]DCR is defined as the percentage of subjects who have achieved complete response (CR), partial response (PR), or stable disease (SD) based on assessments per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- Duration of Response (DOR) [ Time Frame: 18 months ]For subjects who demonstrate CR or PR, based on assessments per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
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): NCT03767439
|Contact: Lisa Olmos, RNfirstname.lastname@example.org|
|Contact: Richard Carvajal, MD.||646 317 email@example.com|
|Principal Investigator:||Richard Carvajal, MD.||Columbia University|