Safety and Tolerability of a Modified Vaccinia Ankara (MVA) Priming Followed by Fowlpox Booster Vaccines Modified to Express Brachyury and T-Cell Costimulatory Molecules (MVA-BN-Brachyury/FPV-Brachyury)

Breast Cancer Clinical Trial

Official title: Safety and Tolerability of a Modified Vaccinia Ankara (MVA) Priming Followed by Fowlpox Booster Vaccines Modified to Express Brachyury and T-Cell Costimulatory Molecules (MVA-BN-Brachyury/FPV-Brachyury)

Status Not yet recruiting

Clinical Trial Summary

Background:

Brachyury controls the expression of other genes in our cells. How this happens is not fully understood. Research shows that in some cancers, brachyury is over-expressed. This may play a role in cancer growth and metastasis. Researchers want to test a vaccine that turns the immune system against brachyury. The vaccine is made up of 2 viruses: Modified Vaccinia Ankara (MVA) and Fowlpox virus (FPV). The goal is to teach the immune system to kill the tumor cells that express the Brachyury protein.

Objectives:

To test if the booster doses of FPV-Brachyury Fowlpox are safe and can improve the immune response and make it last longer in people with advanced cancer.

Eligibility:

Adults 18 85 years old with cancer that has not responded to standard therapies.

Design:

Participants will be screened with medical history, review of their tumor sample, and physical exam. They will have blood and urine tests. They will have scans and X-rays to assess their cancer. They will have a heart test.

Participants will get the vaccine in shots under the skin, close to lymph nodes. Shots will be given every 4 12 weeks for 2 years as long as participants can and are willing to continue to participate. At these visits, they will repeat some or all the screening tests, except the tumor sample review.

After 2 years, participants will get phone calls every 3 months for 5 years. They will talk about any symptoms they have had.

Clinical Trial Description

Background:

• MVA/FPV-Brachyury-TRICOM is a novel recombinant vector-based therapeutic cancer vaccine comprising a priming vector, Modified Vaccinia Ankara (MVA-brachyury-TRICOM), and a boost vector, fowlpox (FPV-brachyury-TRICOM), designed to induce an enhanced immune response against brachyury, which is overexpressed in many solid tumor types, such as lung, breast, ovarian, chordoma, prostate, colorectal, and pancreatic adenocarcinoma.

• Modified Vaccinia Ankara (MVA) is a replication-deficient, attenuated derivative of vaccinia. It is used in the smallpox vaccination and is now being developed as a recombinant viral vector to produce vaccines against infectious diseases and cancer. Fowlpox is also replication incompetent in human cells and can be used for multiple booster vaccinations due to weak host-neutralizing antibody responses against the vector.

• Poxviral vaccines delivering a triad of three human T-cell costimulatory molecules designated TRICOM (B7.1, ICAM-1 and LFA-3) have been extensively studied in both preclinical and clinical studies and have demonstrated their ability to induce robust Tcell activation and provide evidence of clinical benefit.

• Brachyury is a member of the T-box family of transcription factors. It is overexpressed in cancer cells compared with normal tissue and has been linked to cancer cell resistance and metastatic potential.

• A previous phase I trial of MVA-brachyury-TRICOM demonstrated immunogenicity and safety of the priming dose and established a recommended phase 2 dose. Evaluation was limited due to the lack of long-term booster dosing.

• This study will evaluate safety and tolerability of MVA-brachyury-TRICOM priming dose followed by FPV-brachyury-TRICOM booster dose (prime-boost strategy)

Objective:

• To determine the safety and tolerability of MVA-brachyury-TRICOM followed by FPVbrachyury-TRICOM vaccine.

Eligibility:

• Histologically confirmed malignancy

• Metastatic or unresectable locally advanced malignant solid tumor. In the case of chordoma, unresectable, locally recurrent, or metastatic tumors are acceptable for enrollment, given that this represents incurable disease. As much as possible, patients enrolled will have tumor types with known increased expression of brachyury (such as lung, breast, ovarian, prostate, colorectal, pancreatic, hepatocellular, Merkel cell, small cell lung cancer or chordoma).

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at study entry

• Age greater than or equal to 18 years.

• Prior Therapy: Completed, or disease progression on at least one prior line of disease-appropriate therapy for metastatic disease, or not a candidate for therapy of proven efficacy for their disease.

Design:

• This is an open-label, phase I trial. One dose level will be evaluated of MVA-brachyury-TRICOM priming vaccine followed by fowlpox-brachyury-TRICOM booster vaccine.

• Up to 10 patients, assuming no more than 1/6 patients experience a dose limiting toxicity, will be treated with 2 doses of MVA-brachyury-TRICOM priming vaccine administered subcutaneously with 4 injections of study drug (1 injection = 2 x 10(8) infectious units (IU) at monthly (28 days +/ 4 days) intervals for 2 months followed by monthly doses of fowlpox-brachyury-TRICOM at 1 x 109 Infectious units (Inf.U) given as a single subcutaneous injection monthly (28 days +/- 4 days).

• If 3 patients per month can be accrued, the study is expected to require 3-4 months to complete the necessary enrollment. ;

Related Conditions & MeSH terms

• Breast Cancer
• Lung Cancer
• Ovarian Cancer
• Prostate Cancer
• Tumors (Others)
• Vaccinia

• NCT number: NCT03411486
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Diana Martin, R.N.
• Phone: (240) 760-7969
• Email: diana.martin@nih.gov
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: February 6, 2018
• Completion date: December 31, 2019