Intratumoral MMR Vaccine Injection in Borderline Resectable/Unresectable Pancreatic Cancer

Brief summary public domain (ClinicalTrials.gov)

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.

Detailed description public domain (ClinicalTrials.gov)

This is a prospective single-arm phase Ib/II study for subjects with locally advanced, borderline resectable / unresectable, non-metastatic pancreatic cancer that remains unresectable following SoC chemotherapy and RT. Patients whose tumors have not become resectable following SoC treatment with chemotherapy and RT will be treated with intratumoral injection of MMR vaccine by endoscopy and endoscopic ultrasound. Patients with unresectable or borderline resectable pancreatic cancer treated via SoC protocol with induction chemotherapy (of physician's choice, e.g., FOLFIRINOX, Gemcitabine + Abraxane, Nab Paclitaxel or NALIRIFOX) followed by radiation (physician's preference) along with chemotherapy (5FU/capecitabine, per physician's choice) will be eligible for the study if the tumor did not become resectable following the therapy just described.

Intervention public domain (ClinicalTrials.gov)

Biological: Intratumoral MMR Injection. A 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.

Arm public domain (ClinicalTrials.gov)

Intratumoral MMR Injection (experimental):

Primary outcome public domain (ClinicalTrials.gov)

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 injection.

Secondary outcome public domain (ClinicalTrials.gov)

The clinical efficacy of MMR vaccines will be assessed according to RECIST 1.1. Time frame: At screening and every 12 weeks from day 1 for 2 years.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: 1. Age ≥ 18 years. 2. Pathologically proven locally advanced adenocarcinoma of pancreas. 3. Borderline resectable pancreatic cancer that is determined to be unresectable following completion of SoC chemotherapy and RT as evidenced by any of the following: 1. 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. 2. Venous involvement of SMV or portal vein, less than 180 degrees. 3. Tumor abutment of SMA, less than half the circumference of the vessel wall. OR Unresectable pancreatic cancer that remains unresectable following completion of SoC chemotherapy and RT as evidenced by any of the following: 4. Greater than 180-degree encasement or occlusion/thrombus of SMA, unresectable SMV, or SMV-portal confluence occlusion. 5. Direct involvement of inferior vena cava, aorta, celiac trunk, or hepatic artery, as defined by the absence of fat plane between low-density tumor and these structures on CT scan. OR Surgeon deems that the pancreatic cancer is unresectable. 4. Prior history of treatment with chemotherapy (e.g., FOLFIRINOX, Gemcitabine + Abraxane or NALIRIFOX \[liposomal irinotecan (Nal-IRI or Onivyde®), Nab Paclitaxel, 5 fluorouracil (5-FU)/leucovorin and oxaliplatin\]) and RT. The chemotherapy regimen is per treating physician's choice. The chemotherapy agent for radio sensitization is up to the treating physician (capecitabine, 5FU or gemcitabine). a. The chemo-radiation therapy regimen should be completed at least 6 weeks but no more than 12 weeks from planned Day 1. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 6. Adequate hematological function (Hemoglobin \> 9g/dL, White Blood Cell (WBC) count \> 1500 K/µL, Absolute Neutrophil Count (ANC) \> 500 K/µL, Platelet count \> 100 K/µL). 7. Adequate hepatic function (Total bilirubin ≤ 1.5 x institutional upper limit of normal \[ULN\]) (Note: In subjects with Gilbert's syndrome, if total bilirubin is \>1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 × ULN, subject is eligible); Aspartate aminotransferase (AST\[SGOT\]) or Alanine aminotransferase (ALT\[SGPT\]) ≤ 2.5 × institutional ULN; Serum albumin ≥ 3.0 g/dL. 8. Adequate renal function (i.e., creatinine less than 1.5 times ULN). Exclusion Criteria: 1. Pancreatic cancer that was either resectable before SoC treatment or became resectable following SoC chemotherapy …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 20 participants (estimated).