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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
39
The target serum level for VPA will be between 75 and 100 mcg/mL checked every 2 weeks for the first 6 cycles.
10 mg/kg IV
Cross Cancer Institute
Edmonton, Alberta, Canada
Efficacy of Avelumab and VPA
• Assessment of the clinical response rate according to the immune-related RECIST criteria (iRECIST)
Time frame: 1 year after enrolment of last patient
Proportion of subjects who complete 4 doses of Avelumab in combination with VPA
• Feasibility analysis, defined as the proportion of subjects who complete 4 doses of Avelumab in combination with VPA over the total duration of the study.
Time frame: 1 year after enrolment of last patient
Overall survival
defined as the time from the date of enrollment to the date of death, whatever the cause.
Time frame: 5 years from final study drug dose
Progression free survival
Progression free survival is defined as the time between the date of treatment initiation and the date of disease progression or death (whatever the cause), whichever occurs first.
Time frame: 5 years from final study drug dose
Number of participants with adverse events
• Incidence of adverse events (assessed as the incidence and severity of adverse events, including immune-related adverse events, and the number of discontinuations due to adverse events).
Time frame: Through study completion, up to 2 years
Identify specific virus-associated cancers as candidates for subsequent study
Time frame: Through study completion, up to 2 years
Measurement of Immuno-score
AffymetriX Micro-array (Immuno-score)
Time frame: Through study completion, up to 2 years
Measurement of MHC expression
Time frame: Through study completion, up to 2 years
Measurement of cell-free tumoral DNA in blood
Time frame: Through study completion, up to 2 years
Phenotyping of Tumour Infiltrating Lymphocytes
Time frame: Through study completion, up to 2 years
DNA viral load
DNA Quantitative PCR (viral load)
Time frame: Through study completion, up to 2 years
Expression of lytic viral genes
Time frame: Through study completion, up to 2 years
Cytotoxic T-Lymphocyte immunophenotyping
Time frame: Through study completion, up to 2 years
T-cell receptor sequencing
Time frame: Through study completion, up to 2 years
Hsp90 concentration in serum
Time frame: Through study completion, up to 2 years
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