Intratumoral MMR Vaccine Injection in Borderline Resectable/Unresectable Pancreatic Cancer
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Arkansas
About this trial
By doing this study, it is the hope to learn whether an injection of the measles, mumps, rubella (MMR) vaccine developed by Merck \& Co. (Merck's M-M-R® II) into the tumor is safe and effective in making the tumor smaller.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years.
Pathologically proven locally advanced adenocarcinoma of pancreas.
Encasement of gastroduodenal artery up to the common hepatic artery/short segment encasement or abutment of the hepatic artery, but without extension to the celiac trunk.
Venous involvement of SMV or portal vein, less than 180 degrees.
Disqualifiers
Pancreatic cancer that was either resectable before SoC treatment or became resectable following SoC chemotherapy and RT.
Subjects with radiographically proven metastatic disease are excluded.
Subject must not be pregnant and/or currently breastfeeding or plan to be.
Subject must not have received any live vaccine, including MMR, within 30 days prior to the dose of study drug.
Trial design
Design model
Single group
Treatments tested in this trial
Intratumoral MMR Injection
Biological/VaccineA single dose (0.5 mililiter) of MMR vaccine will be injected under endoscopic ultrasound guidance in the GI laboratory at UAMS under sedation as prescribed by the interventional gastroenterologist. The injection will be at least 6 weeks but no later than 12 weeks post completion of chemo-radiation therapy.
Treatment groups
20 Participants
are divided into 1 treatment groupGroup A: Intratumoral MMR InjectionExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Intratumoral T-Cell Response
Intratumoral T-cell Response (iTCR) will be defined as a change of greater than 2-fold increase in the frequency of IFNγ-positive T- cells in the repeat (4 week) tumor biopsy relative to the first (baseline) tumor biopsy. Each subject will be scored Yes or No for if they achieved iTCR. Subjects that decline the repeat tumor biopsy will be scored Not Evaluable (NE) for iTCR.
Time frame
Baseline to 4 weeks post injectionSecondary outcomes
1
The clinical efficacy of MMR vaccines will be assessed according to RECIST 1.1
A subject's Progression Free Survival (PFS) will be defined as the time in months from the date when their tumor is injected with MMR vaccine to the date on which they either die or experience documented progressive disease (whichever occurs first). Subjects that are alive and progression-free on their date of at last contact will be right-censored for PFS. A subject's Overall Survival will be defined as the time in months from the date when their tumor is injected with MMR vaccine to the date on which they die. Subjects that are still alive at last contact will be right censored for OS.
Time frame
At screening and every 12 weeks from day 1 for 2 yearsOther outcomes
1
Immune response dynamics following treatment with MMR
T cell function will be at screening, Day 1, Day 8, Week 4 and Week 8 using PBMCs isolated from subject samples. Functional assays will include flow cytometry to assess T cell subsets including CD4 and CD8 T cells along with activation markers like CD69 and CD25. Markers of T cell exhaustion such as PD1, CTLA4, LAG3, VISTA and TIM3 will be analyzed to assess immune dysfunction and potential resistance to treatment. Intracellular cytokine staining will measure IFN gamma TNF alpha and IL2 production as indicators of immune response. ELISPOT assays will quantify antigen specific T cell responses while proliferation assays using CFSE dilution will evaluate T cell expansion. RNA sequencing and multiplex cytokine profiling will help characterize transcriptional and secretory profiles related to T cell activation exhaustion and memory formation. The FNA samples will used to study gene signatures
Time frame
From MMR injection to week 8Sponsors and contacts
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Source ClinicalTrials.gov