Avelumab With Valproic Acid in Virus-associated Cancer (LATENT)
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|ClinicalTrials.gov Identifier: NCT03357757|
Recruitment Status : Recruiting
First Posted : November 30, 2017
Last Update Posted : June 12, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|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 EBER Positive NPC EBER Positive Hodgkins and Non-hodgkins Lymphona||Drug: Valproic Acid Biological: Avelumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||39 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||February 7, 2018|
|Estimated Primary Completion Date :||October 31, 2021|
|Estimated Study Completion Date :||February 26, 2027|
Experimental: Avelumab with VPA
Valproic Acid (VPA, 12.5 mg/kg) once per day and Avelumab (10 mg/kg IV) every 2 weeks for up to 2 years.
Drug: Valproic Acid
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
- 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.
- Overall survival [ Time Frame: 5 years from final study drug dose ]defined as the time from the date of enrollment to the date of death, whatever the cause.
- Progression free survival [ Time Frame: 5 years from final study drug dose ]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.
- Number of participants with adverse events [ Time Frame: Through study completion, up to 2 years ]• 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).
- 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 ]AffymetriX Micro-array (Immuno-score)
- 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 ]DNA Quantitative PCR (viral load)
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03357757
|Contact: John Walker, MD PhD FRCPC||780-432-8340||mailto:John.Walker2@albertahealthservices.ca|
|Cross Cancer Institute||Recruiting|
|Edmonton, Alberta, Canada, T6G 1Z2|
|Principal Investigator:||John Walker, MD PhD FRCPC||Alberta Health Services|