Cancer That is Associated With a Chronic Viral InfectionPhase 2LATENTNCT03357757
Avelumab With Valproic Acid in Virus-associated Cancer
A Phase 2 study testing Valproic Acid and Avelumab in people with Cancer That is Associated With a Chronic Viral Infection and p16 Positive SCCHN, run by AHS Cancer Control Alberta at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer That is Associated With a Chronic Viral Infection, p16 Positive SCCHN, Squamous Cell Carcinoma of the Cervix
- What is being tested?
- Valproic Acid and Avelumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteCanada
- Study dates
- 7 Feb 2018to 31 Mar 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must be 18 years of age or older.
- Patients with the following histologically confirmed diagnoses will be eligible for enrolment: 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.
- Note: patients with p16 positive SCC of unknown primary origin meeting the minimum life expectancy and performance status requirements will also be eligible for enrollment, as the majority of these patients may be assumed to represent HPV-associated disease.
- Patients must be capable of providing consent to enrolment and treatment.
- Patients with a performance status of ECOG 0-1(51) will be eligible for enrolment (see appendix 1).
- Measurable disease must be present according to irRECIST criteria(50).
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- Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test at the time of screening.
- Patients of childbearing / reproductive potential should use highly effective birth control methods, as defined by the investigator, during the study treatment period and for a period of 60 days after the last dose of study drug. A highly effective method of birth control is defined as those that result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.
- Note: abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard.
- Female patients who are breast-feeding should discontinue nursing prior to the first dose of study treatment and until 120 days after the last dose of study drug.
- Absence of any condition hampering compliance with the study protocol and follow- up schedule; those conditions should be discussed with the patient before registration in the trial.
- The following adequate organ function laboratory values must be met:
- Hematological:
- Absolute neutrophil count (ANC) >1.5 x109/L
- Platelet count >100 x109/L
- Hemoglobin >9 g/dL (may have been transfused)
- Renal:
- o Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
- Hepatic:
- Total serum bilirubin <1.5x ULN
- AST and ALT <2.5x ULN (or ≤ 5 x ULN for subjects with documented metastatic disease to the liver)
- Serum albumin > 25 g/L
- Coagulation:
- International Normalized Ratio (INR) <1.5x ULN (unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants)
- Activated Partial Thromboplastin Time (aPTT) <1.5x ULN (unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants)
Who cannot join
- History of pneumonitis requiring treatment with steroids.
- History of interstitial lung disease.
- Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
- History of another malignancy or a concurrent malignancy;
- Exceptions include patients who have been disease-free for 5 years, or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ.
- Active brain metastases or leptomeningeal disease.
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- Patients with treated brain metastases that are stable for 6 weeks will be eligible for enrolment.
- Diagnosis of immunodeficiency.
- Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
- Prior organ transplantation including allogenic stem-cell transplantation.
- Known history of human immunodeficiency virus (HIV).
- Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
- Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
- Patients with hyperthyroidism or hypothyroidism but that are stable on hormone replacement will not be excluded.
- Active infection requiring systemic therapy.
- Vaccination within 4 weeks of the first dose of Avelumab and while on trials is prohibited except for administration of inactivated vaccines.
- Patient will not be eligible if the patient is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific subject.
- Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
- Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3).
- Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- Cancer That is Associated With a Chronic Viral Infection, 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
- Being tested
- Valproic Acid, Avelumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Valproic AcidDrug
The target serum level for VPA will be between 75 and 100 mcg/mL checked every 2 weeks for the first 6 cycles.
AvelumabBiological
10 mg/kg IV
| Study group | Role | What they receive |
|---|---|---|
| Avelumab with VPA | Experimental | Valproic Acid (VPA, 12.5 mg/kg) once per day and Avelumab (10 mg/kg IV) every 2 weeks for up to 2 years. Receives: Drug: Valproic Acid; Biological: Avelumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of Avelumab and VPA
- Assessment of the clinical response rate according to the immune-related RECIST criteria (iRECIST)
Measured: 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.
Measured: 1 year after enrolment of last patient
Secondary outcomes (13)
Overall survival
defined as the time from the date of enrollment to the date of death, whatever the cause.
Measured: 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.
Measured: 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).
Measured: Through study completion, up to 2 years
Identify specific virus-associated cancers as candidates for subsequent study
Measured: Through study completion, up to 2 years
Measurement of Immuno-score
AffymetriX Micro-array (Immuno-score)
Measured: Through study completion, up to 2 years
Measurement of MHC expression
Measured: Through study completion, up to 2 years
Measurement of cell-free tumoral DNA in blood
Measured: Through study completion, up to 2 years
Phenotyping of Tumour Infiltrating Lymphocytes
Measured: Through study completion, up to 2 years
DNA viral load
DNA Quantitative PCR (viral load)
Measured: Through study completion, up to 2 years
Expression of lytic viral genes
Measured: Through study completion, up to 2 years
Cytotoxic T-Lymphocyte immunophenotyping
Measured: Through study completion, up to 2 years
T-cell receptor sequencing
Measured: Through study completion, up to 2 years
Hsp90 concentration in serum
Measured: Through study completion, up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2017
- Study start7 Feb 2018
- Primary completion30 Mar 2022
- Study completion31 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cancer That is Associated With a Chronic Viral InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- AHS Cancer Control Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- EMD Serono
- Responsible party
- Sponsor
- Investigators
- John Walker, MD PhD FRCPC, Principal investigator, Alberta Health services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03357757
- Sponsor's protocol ID
- LATENT
- Acronym
- LATENT
- Status last verified
- Nov 2026
- First submitted
- 16 Nov 2017
- Last updated
- 4 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03357757
- Acronym / sponsor ID
- LATENT / LATENT
- Conditions
- Cancer That is Associated With a Chronic Viral Infection, 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- AHS Cancer Control AlbertaUniversity, hospital or other
- Collaborators
- EMD Serono
- Study start
- 7 Feb 2018 (actual)
- Primary completion
- 30 Mar 2022 (actual)
- Study completion
- 31 Mar 2025 (actual)
- First posted
- 30 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Avelumab with VPA | Experimental | Drug: Valproic Acid, Biological: AvelumabValproic Acid (VPA, 12.5 mg/kg) once per day and Avelumab (10 mg/kg IV) every 2 weeks for up to 2 years. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Patients must be 18 years of age or older.
- Patients with the following histologically confirmed diagnoses will be eligible for enrolment: 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.
- Note: patients with p16 positive SCC of unknown primary origin meeting the minimum life expectancy and performance status requirements will also be eligible for enrollment, as the majority of these patients may be assumed to represent HPV-associated disease.
- Patients must be capable of providing consent to enrolment and treatment.
- Patients with a performance status of ECOG 0-1(51) will be eligible for enrolment (see appendix 1).
Key exclusion criteria (20 listed)
- History of pneumonitis requiring treatment with steroids.
- History of interstitial lung disease.
- Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
- History of another malignancy or a concurrent malignancy;
- Exceptions include patients who have been disease-free for 5 years, or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Valproic AcidThe target serum level for VPA will be between 75 and 100 mcg/mL checked every 2 weeks for the first 6 cycles. | Drug | Avelumab with VPA |
| Avelumab10 mg/kg IV | Biological | Avelumab with VPA |
Primary outcome
Efficacy of Avelumab and VPA
Time frame: 1 year after enrolment of last patient
• Assessment of the clinical response rate according to the immune-related RECIST criteria (iRECIST)
Proportion of subjects who complete 4 doses of Avelumab in combination with VPA
Time frame: 1 year after enrolment of last patient
• 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.
13 secondary outcomes
Overall survival
Time frame: 5 years from final study drug dose
Progression free survival
Time frame: 5 years from final study drug dose
Number of participants with 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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Walker, MD PhD FRCPC principal investigator
Alberta Health services
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Valproic Acid and Avelumab in people with Cancer That is Associated With a Chronic Viral Infection and p16 Positive SCCHN, run by AHS Cancer Control Alberta at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of Avelumab and VPA (time frame: 1 year after enrolment of last patient). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026; AzTrials last refreshed its copy on 6 Nov 2026.