Imvamune Vaccine for the Treatment of Non-melanoma Skin Cancer (MUSIC-01)

MVA-BN Imvamune Smallpox Vaccine Virus for Treatment of Basal Cell Carcinoma, Squamous Cell Carcinomas

This study examines the safety and efficacy of using the Imvamune smallpox vaccine in the treatment of non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma).

Study Overview

• Status: Terminated
• Conditions: Basal Cell Carcinoma; Squamous Cell Carcinoma; Non-melanoma Skin Cancer
• Intervention / Treatment: Biological: Imvamune

Detailed Description

One of the main ways cancer is able to develop is by hiding or evading our immune system which usually detects and kills potential tumor cells. Once cancer has developed the ability to evade the immune system it can continue to grow and become a tumor. One potential strategy currently being researched, called immunotherapy, uses viruses to stimulate an immune response which attacks the tumor.

Imvamune is a live, non-replicating virus used in Canada to vaccinate adults and children against smallpox. It is safe to use in immunosuppressed patients because the virus is unable to replicate and spread past the first infected cell. This makes the Imvamune vaccine a viable candidate for immunotherapy in immunosuppressed patients who are at a much higher (up to 60x) risk of developing non-melanoma skin cancers.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ivan V. Litvinov, M.D., Ph.D; Phone Number: 76140 514-934-1934; Email: ivan.litvinov@mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada
      • McGill University Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects must have histologically confirmed, BCC and/or SCC tumors located on the chest, back, thigh, or arm/forearm.
• Presence of clinically documented disease. Skin tumor should measure at least 10 mm in size and should be no larger than 5 cm in any axes. There should be no clinical suspicion of metastasis (i.e. no lymphadenopaties and no systemic symptoms).
• Age > 18 years.
• Subjects must have a documented ECOG performance status of 0 or 1.
• Subjects could be treatment naive or could have had previous surgery or radiation
• Subjects may have had prior radiation therapy. A minimum of 28 days (4 weeks) must have elapsed between the last dose of radiation and date of registration (14 days for a single palliative fraction of radiation to a non-target lesion). Subjects must have recovered from any acute toxic effects from radiation prior to registration (unless grade 1, irreversible and considered not clinically significant).
• Previous surgery is permitted. A minimum of 28 days (4 weeks) must have elapsed between any major surgery and date of registration (7 days for minor surgery), provided that wound healing has occurred
• Each subject must sign a consent form prior to registration/at registration and prior to tests which are study specific.
• Subjects must be accessible for treatment and follow-up. Subjects registered on this trial must be treated and followed at the McGill University Health Centre (MUHC) or McGill Affiliated/other participating hospitals
• Laboratory requirements (must be done within 7 days prior to registration or at time of registration) as follows:
• White blood cell count ≥3.0x10^9/L
• absolute neutrophils ≥1.5x10^9/L
• hemoglobin ≥100g/L
• platelets ≥75x10^9/L
• INR ≤1.2
• bilirubin ≤1.5x upper normal limit
• AST and ALT ≤3.0x upper normal limit
• serum creatinine ≤1.5x upper normal limit (or creatinine clearance of ≥60mL/min)

Exclusion Criteria:

• Cancers located on cosmetically/functionally important areas (i.e. face, neck, genitalia, hands, feet, and lower legs).
• Tumor larger than 5 cm in size (any axes).
• Metastatic disease (or suspicion of metastasis).
• Tumors arising as part of a genetic syndrome (i.e., Bazex-Dupré-Christol, Basal Cell Nevus Syndrome, Rombo syndromes for BCC or Xeroderma Pigmentosa, Ferguson Smith, Grzybowski, Muir-Tore syndromes for SCC).
• Immunosuppressed individuals (e.g. organ transplant recipients, patient with inherited immunodeficiencies, HIV+ individuals or individuals receiving immunosuppressive medications for other reasons).
• Individuals that are not able or willing to sign an informed consent.
• Subjects with history of other active or current malignancies requiring active treatment.
• Patients undergoing concurrent treatments with other anti-cancer therapy or other investigational agents.
• Subjects with prior treatment with Imvamune
• Subjects with serious illness or medical condition that would not permit management
• Subjects with uncontrolled pre-existing cardiovascular conditions and/or symptomatic cardiac dysfunction.
• Pregnant or lactating women. Men or women of childbearing potential who do not agree to use adequate contraception while on trial and 6 weeks following the trial.
• Subjects using anti-viral medications, steroids, immunosuppressive agents, or immunization (including the flu shot) within 14 days prior to registration. Patients who are at high risk of influenza infection (65 years and older, people of any age with certain chronic medical conditions (such as asthma, diabetes, or heart disease), pregnant women and children younger than 5 years), and who have not received an influenza vaccination during the flu season (i.e., October to May).
• Subjects with a condition that could have resulted in splenic dysfunction (e.g. splenectomy, sickle cell anemia, radiation to the spleen ≥ 20Gy, congenital asplenism).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Imvamune; Imvamune vaccine to be administered intratumorally at one of three doses on Days 0 and 4 of the study	Biological: Imvamune; Imvamune vaccine to be administered (via injection) intratumorally at one of three doses (1x10^7, 1x10^8, or 4x10^8 PFU) twice, 4 days apart (first injection on Day 0 of the study and second injection on Day 4); Other Names: MVA-BN Smallpox vaccine; Modified Vaccinia Ankara Smallpox Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD)	The MTD will be defined as the dose at which 2 or more patients experience a grade 3 or 4 adverse event (as defined by NCI Common Terminology Criteria for Adverse Events version 5.0) that is at least "probably related" to the study drug (ex: dose limiting toxicity).	25 days
Objective Tumor Response Rate (ORR)	Clinical and histological evaluation of the tumor to assess the development of immunity against BCC and/or SCC tumors or their protein markers.	25 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral load in NMSC tumours	Ability to detect viral infection in the tumor.	25 days
Number of T cells/concentration of antigen specific antibodies	Ability to elicit increased immunological T/NKT cell mediated response, and antibody response against the tumor.	25 days

Collaborators and Investigators

• Sponsor: Ivan Litvinov
• Investigators: Principal Investigator: Ivan V Litvinov, M.D., Ph.D, McGill University Health Centre/Research Institute of the McGill University Health Centre

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2020
• Primary Completion (Actual): May 23, 2023
• Study Completion (Actual): May 23, 2023

Study Registration Dates

• First Submitted: May 27, 2020
• First Submitted That Met QC Criteria: May 27, 2020
• First Posted (Actual): June 1, 2020

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; Skin Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Neoplasms, Basal Cell; Carcinoma; Carcinoma, Squamous Cell; Skin Neoplasms; Carcinoma, Basal Cell; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Immunologic Factors; Vaccines; Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
• Other Study ID Numbers: 2020-4599

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No