MC1641 Phase II Study Of Intratumoral Injection Of Autologous Dendritic Cells Combined With Immune Checkpoint Inhibition After High-Dose Conformal External Beam Radiotherapy In Patients With Unresectable Primary Liver Cancer
This early phase I trial studies the side effects of autologous dendritic cells and a vaccine called Prevnar in combination with immune checkpoint inhibition (with bevacizumab and atezolizumab or atezolizumab and tiragolumab) in treating patients liver cancer that cannot be removed by surgery (unresectable) after undergoing standard high-dose external beam radiotherapy. Autologous dendritic cells are immune cells generated from patients' own white blood cells that are grown in a special lab and trained to stimulate the immune system to destroy tumor cells. A pneumonia vaccine called Prevnar may also help stimulate the immune system. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Immunotherapy with monoclonal antibodies, such as atezolizumab and tiragolumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving autologous dendritic cells and Prevnar in combination with immune checkpoint inhibition after radiotherapy may be safe, and tolerable and may stimulate the body's own immune system to fight against the tumor in patients with unresectable liver cancer.
• Age \>= 18 years
• Pilot study (group 1): Histologic confirmation of intrahepatic CCA (Closed as of amendment 3)
• Phase II study (group 2): Histologic and/or radiologic confirmation of hepatocellular carcinoma (HCC)
• Phase II study (group 3): Histologic confirmation of intrahepatic cholangiocarcinoma (iCCA)
• The following tumor characteristics must be met
‣ Unresectable disease: HCC (group 2) or intrahepatic CCA (group 3)
⁃ Measurable or evaluable disease
⁃ All lesions should be treatable by EBRT while meeting normal tissue constraints
⁃ Tumor lesions should be accessible using an ultrasound (US)-guided approach for intratumoral DC injection
⁃ No evidence of extrahepatic tumor (excluding tumor thrombus) by computed tomography (CT) or magnetic resonance imaging (MRI) scan
∙ NOTE: Patients who are not candidates for surgical treatment or for ablation with curative intent are allowed
• Good candidate for standard of care high-dose conformal EBRT in the view of the investigator
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• GROUP 2 HCC ONLY: Absolute neutrophil count (ANC) \>= 1000/mm\^3 (obtained =\< 15 days prior to registration)
• GROUP 2 HCC ONLY: Absolute lymphocyte count (ALC) \>= 500/mm\^3 (obtained =\< 15 days prior to registration)
• GROUP 2 HCC ONLY: Absolute monocyte count (AMC) \>= 300/mm\^3 (obtained =\< 15 days prior to registration)
• GROUP 2 HCC ONLY: Platelet count \>= 50,000/mm\^3 (obtained =\< 15 days prior to registration)
• GROUP 2 HCC ONLY: Hemoglobin \>= 9.0 g/dL (obtained =\< 15 days prior to registration)
• GROUP 2 HCC ONLY: Total bilirubin \< 1.5 mg/dL (obtained =\< 15 days prior to registration)
• GROUP 2 HCC ONLY: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 5 x upper limit of normal (ULN) (obtained =\< 15 days prior to registration)
• GROUP 2 HCC ONLY: Creatinine =\< 2 mg/dL (obtained =\< 15 days prior to registration)
• GROUP 2 HCC ONLY: Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (obtained =\< 15 days prior to registration)
• GROUP 2 HCC ONLY: Absence of proteinuria at screening as demonstrated by one of the following:
‣ Urine protein/creatinine (UPC) ratio \< 1.0 at screening OR
⁃ Urine dipstick for proteinuria \< 2+ (patients discovered to have \>= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate =\<1g of protein in 24 hours to be eligible)
• GROUP 3 iCCA ONLY: Absolute neutrophil count (ANC) ≥ 1500/mm\^3 (obtained =\< 15 days prior to registration)
• GROUP 3 iCCA ONLY: Absolute lymphocyte count ≥ 500/mm\^3 (obtained =\< 15 days prior to registration)
• GROUP 3 iCCA ONLY: Absolute monocyte count ≥ 300/mm\^3 (obtained =\< 15 days prior to registration)
• GROUP 3 iCCA ONLY: Platelet count ≥ 100,000/mm\^3 (obtained =\< 15 days prior to registration)
• GROUP 3 iCCA ONLY: Hemoglobin ≥ 9.0 g/dL (obtained =\< 15 days prior to registration)
• GROUP 3 iCCA ONLY: Total bilirubin \< 1.5 x ULN (obtained =\< 15 days prior to registration)
• GROUP 3 iCCA ONLY: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and alkaline phosphatase (ALP) ≤ 2.5 x ULN (obtained =\< 15 days prior to registration)
• GROUP 3 iCCA ONLY: Creatinine ≤ 2 mg/dL (obtained =\< 15 days prior to registration)
• GROUP 3 iCCA ONLY: Serum albumin ≥ 25 g/L (2.5 g/dL) (obtained =\< 15 days prior to registration)
• GROUP 3 iCCA ONLY: PT/INR/aPTT ≤ 1.5 x ULN (obtained =\< 15 days prior to registration)
‣ NOTE: If patient is receiving therapeutic anticoagulation, patient must be on a stable anticoagulant regimen
• GROUP 3 iCCA ONLY: Calcium ≤ 12 mg/dl or corrected serum calcium ≤ ULN (obtained =\< 15 days prior to registration)
• Negative pregnancy test done =\< 8 days prior to registration, for persons of childbearing potential only
• GROUP 3 ONLY: Negative hepatitis B surface antigen (HBsAg) test at screening
• GROUP 3 ONLY: Negative hepatitis C virus antibody (HCV Ab) test at screening, or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening. (NOTE: HCV RNA test will be performed only for patients who have a positive HCV antibody test.)
• Ability to provide written consent
• Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• Willingness to provide blood and tissue samples for correlative research purposes