What is the mechanism of action of this treatment?

Valproic acid and Avelumab are promising treatments for viral-associated cancers due to their unique mechanisms of action. Valproic acid unmask chronic viral infections, making the virus more detectable by the immune system, which is essential since many viral-associated cancers arise from viruses that evade immune detection. Avelumab, an immune checkpoint inhibitor, prevents the deactivation of lymphocytes, thereby maintaining a robust immune response against cancer cells. This combination enhances the immune system's ability to recognize and attack cancer cells linked to viral infections, offering a targeted approach to treatment.

What side effects are associated with this type of intervention?

Valproic acid, used to unmask chronic viral infections, can cause gastrointestinal disturbances, liver toxicity, and blood disorders. Avelumab, an immune checkpoint inhibitor, may lead to immune-related adverse effects such as thyroid dysfunction, colitis, pneumonitis, and uveitis. Combining these treatments aims to boost the immune response against cancer but may increase the risk of immune-related side effects.

What prior FDA approvals exist?

FDA-approved treatments for viral-associated cancers include immune checkpoint inhibitors like Pembrolizumab and Nivolumab, which target PD-1/PD-L1 pathways to prevent the deactivation of lymphocytes, similar to Avelumab. These drugs have shown efficacy in various cancers, including those associated with viral infections such as HPV-related cancers. While specific FDA approvals for drugs that unmask chronic viral infections like Valproic acid are less common, the combination of immune checkpoint inhibitors with other agents to enhance immune response is a growing area of research.

What other types of research exist?

Promising alternatives to Valproic acid and Avelumab for viral-associated cancer patients include Brentuximab vedotin, which targets CD30-positive cancers, and immune checkpoint inhibitors like Pembrolizumab and Nivolumab, which prevent lymphocyte deactivation and enhance immune response.

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Monoclonal Antibodies

Avelumab + Valproic Acid for Viral Associated Cancer (LATENT Trial)

Phase 2

Waitlist Available

Led By John Walker, MD PhD FRCPC

Research Sponsored by AHS Cancer Control Alberta

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients with histologically confirmed diagnoses including p16 positive SCCHN, squamous cell carcinoma of the cervix, p16 positive squamous cell carcinoma of the vagina or vulva, p16 positive squamous cell carcinoma of the penis, p16 positive squamous cell carcinoma of the anus or anal canal, EBER positive NPC, EBER positive Hodgkins and non-hodgkins lymphoma, and p16 positive SCC of unknown primary origin meeting the minimum life expectancy and performance status requirements

Adequate organ function laboratory values must be met for hematological, renal, hepatic, and coagulation parameters

Must not have

History of interstitial lung disease

Diagnosis of immunodeficiency

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 5 years from final study drug dose

Awards & highlights

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial is testing a combination of Valproic acid and Avelumab to treat cancers linked to chronic viral infections. Valproic acid helps reveal these hidden infections, while Avelumab keeps immune cells active to fight the cancer more effectively. Avelumab has shown promise in treating various cancers, including non-small cell lung cancer, genitourinary tumors, and urothelial carcinoma.

Who is the study for?

Adults with certain virus-associated cancers (like HPV-related cervical or oral cavity cancer) can join this trial. They must have specific types of squamous cell carcinoma or lymphoma, be able to consent, and meet blood count and organ function criteria. Women who can get pregnant need a negative pregnancy test and must use effective birth control.

What is being tested?

The trial is testing Valproic Acid combined with Avelumab, an immune therapy drug. Valproic Acid may expose chronic viral infections to the immune system while Avelumab activates immune cells to potentially enhance the body's defense against cancer.

What are the potential side effects?

Possible side effects include reactions related to the immune system such as inflammation in various organs, infusion reactions which are symptoms that occur during or after receiving a drug intravenously, fatigue, digestive issues like nausea or diarrhea, changes in blood counts leading to increased risk of infections or bleeding.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have a specific type of cancer that is p16 or EBER positive.

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My blood, kidney, liver, and clotting tests are within normal ranges.

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I am 18 years old or older.

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I am able to understand and agree to the study's requirements.

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I can carry out all my usual activities without help.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of lung scarring or fibrosis.

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I have been diagnosed with an immune system disorder.

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I have or had another type of cancer.

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I have active cancer spread to my brain or its coverings.

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I have had an organ or stem-cell transplant.

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I have a serious heart condition.

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I have an autoimmune disease that could worsen with immune-boosting treatments.

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I have a history of HIV, hepatitis B, or hepatitis C.

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I am currently on medication for an infection.

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I have had lung inflammation treated with steroids.

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I have lasting side effects from previous treatments that are mild.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 5 years from final study drug dose

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~5 years from final study drug dose

This trial's timeline: 3 weeks for screening, Varies for treatment, and 5 years from final study drug dose for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Efficacy of Avelumab and VPA

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

Secondary study objectives

DNA viral load

Measurement of Immuno-score

Number of participants with adverse events

+2 more

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Avelumab with VPAExperimental Treatment2 Interventions

Valproic Acid (VPA, 12.5 mg/kg) once per day and Avelumab (10 mg/kg IV) every 2 weeks for up to 2 years.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Avelumab

FDA approved

Valproic acid

FDA approved

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Valproic acid and Avelumab are promising treatments for viral-associated cancers due to their unique mechanisms of action. Valproic acid unmask chronic viral infections, making the virus more detectable by the immune system, which is essential since many viral-associated cancers arise from viruses that evade immune detection. Avelumab, an immune checkpoint inhibitor, prevents the deactivation of lymphocytes, thereby maintaining a robust immune response against cancer cells. This combination enhances the immune system's ability to recognize and attack cancer cells linked to viral infections, offering a targeted approach to treatment.