Nivolumab With Vismodegib in Patients With Basal Cell Nevus Syndrome

NCT03767439 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: AAAS1021
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Basal Cell Nevus Syndrome

Keywords

Nivolumab; Vismodegib; Basal Cell; Basal Cell Nevus Syndrome (BCNS)

Outcome Measures

Primary Outcomes (1)

• Disease control rate

  Defined as the percentage of patients achieving a total tumor burden \<50% of baseline tumor burden

  18 months

Secondary Outcomes (3)

• Total Number of Adverse Reactions

  18 months

• Disease Control Rate (DCR)

  18 months

• Duration of Response (DOR)

  18 months

Study Arms (1)

Nivolumab, Vismodegib, Ipilimumab

EXPERIMENTAL

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.

Drug: Vismodegib; Drug: Nivolumab; Drug: Ipilimumab

Interventions

Vismodegib DRUG

150 mg PO daily

Also known as: ERIVEDGE

Nivolumab, Vismodegib, Ipilimumab

Nivolumab DRUG

480 mg IV every 4 weeks

Also known as: OPDIVO

Nivolumab, Vismodegib, Ipilimumab

Ipilimumab DRUG

1 mg/kg IV every 6 weeks

Also known as: YERVOY

Nivolumab, Vismodegib, Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• or more surgically eligible BCCs (SEBS) within the prior 2 years
• Age \> 16 years
• Karnofsky Performance Score (KPS) \> 60%, Eastern Cooperative Oncology Group (ECOG) \< 2
• Prior SMO inhibitor therapy is permitted, but patients must have developed new and/or progressive lesions on or after therapy
• Adequate organ function
• All clinically significant toxicities from prior systemic therapy must be \< Grade 1
• Subjects must agree to undergo four serial tumor biopsies (may be of different tumors) at baseline, after a two week run-in of Vismodegib, between 4-6 weeks of concurrent Nivolumab and Vismodegib, and at the time of disease recurrence or progression.

You may not qualify if:

• Prior therapy with an immunological checkpoint inhibitor
• Prior SMO inhibitor therapy is permitted, but patients must have developed new and/or progressive lesions on or after therapy
• Routine use of topical (applied to \>5% of skin) or systemic therapies that might interfere with evaluation of the study medication in the prior 4 weeks
• Topical corticosteroids
• Systemic or topical retinoids e.g., etretinate, isotretinoin, tazarotene, tretinoin, adapalene
• Topical alpha-hydroxy acids e.g., glycolic acid, lactic acid
• Systemic or topical 5-fluorouracil or imiquimod to skin above the knees
• Patients who have not recovered from adverse events (\> Grade 1) due to prior treatments
• Treatment with any other investigational agents
• Known history of hypersensitivity to any of the ingredients in the study medication formulations
• Requirement for immunosuppressive corticosteroids at doses exceeding 10 mg prednisone daily or equivalent prior to first dose of Nivolumab
• Ongoing or recent (within 5 years) evidence of significant autoimmune disease at baseline or associated with prior therapy requiring treatment with systemic immunosuppressive treatments with the exception of:
• Viligo
• Childhood asthma that has resolved
• Residual endocrinopathies requiring replacement therapy

Sponsors & Collaborators

• Columbia University: lead

MeSH Terms

Conditions

Basal Cell Nevus Syndrome

Interventions

HhAntag691; Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Odontogenic Cysts; Jaw Cysts; Bone Cysts; Cysts; Neoplasms; Carcinoma, Basal Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Basal Cell; Neoplastic Syndromes, Hereditary; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Jaw Diseases; Stomatognathic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Richard Carvajal, MD.

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine at the Columbia University Medical

Study Record Dates

• First Submitted: December 5, 2018
• First Posted: December 6, 2018
• Study Start: July 1, 2019
• Primary Completion: December 1, 2019
• Study Completion: February 1, 2020
• Last Updated: December 18, 2019

Record last verified: 2019-12