Avelumab With Valproic Acid in Virus-associated Cancer

Official Title

The LATENT Trial: Lytic Activation To Enhance Neoantigen-directed Therapy A Study to Evaluate the Feasibility and Efficacy of the Combined Use of Avelumab With Valproic Acid for the Treatment of Virus-associated Cancer

Summary:

Up to 20% of all cancers may be associated with a bacterial or viral infection. In some instances, the infection may be one of the reasons why the cancer developed in the first place. One such example is infection with the human papilloma virus (HPV) and the development of cervical or oral cavity cancer. A viral infection that is chronic may not cause a person symptoms, and may be able to escape detection by a person's own immune system. One of the medications being studied in this clinical trial (Valproic acid) may be able to unmask a chronic viral infection from a person's own immune system, therefore making the virus susceptible to attack by the immune system. In this study Valproic acid is being combined with an immune therapy, Avelumab. Avelumab is an antibody that targets a person's own immune cells, or lymphocytes. Lymphocytes must be activated to fight infections or cancer, but after activation they are deactivated. Avelumab prevents the deactivation of a lymphocyte, in effect "turning off the off-switch." This leads to a re-energizing of a person's immune system, hopefully leading to an attack by the immune system on a person's cancer. Avelumab is known to be an effective treatment for a variety of cancers, although it has not yet been tested in all cancers. By combining Valproic acid, a treatment which targets the virus that contributed to the development of this type of cancer with Avelumab the investigators hope to enhance the ability of Avelumab to restore the body's own immune defense against the cancer.

Trial Description

Primary Outcome:

• Efficacy of Avelumab and VPA
• Proportion of subjects who complete 4 doses of Avelumab in combination with VPA

• Overall survival
• Progression free survival
• Number of participants with adverse events
• Identify specific virus-associated cancers as candidates for subsequent study
• Measurement of Immuno-score
• Measurement of MHC expression
• Measurement of cell-free tumoural DNA in blood
• Phenotyping of Tumour Infiltrating Lymphocytes
• DNA viral load
• Expression of lytic viral genes
• Cytotoxic T-Lymphocyte immunophenotyping
• T-cell receptor sequencing
• Hsp90 concentration in serum

View this trial on ClinicalTrials.gov