Modified Immune Cells (Autologous Dendritic Cells) and a Vaccine (Prevnar) Combined With Immune Checkpoint Inhibition After High-Dose External Beam Radiation Therapy in Treating Patients With Unresectable Liver Cancer

Recruiting now · Phase 1/Phase 2

Conditions studied: Stage III Hepatocellular Carcinoma AJCC v8, Stage III Intrahepatic Cholangiocarcinoma AJCC v8, Stage IV Hepatocellular Carcinoma AJCC v8, Stage IV Intrahepatic Cholangiocarcinoma AJCC v8, Unresectable Hepatocellular Carcinoma, Unresectable Intrahepatic Cholangiocarcinoma

In brief

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 druvalumab) 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 durvalumab, 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.

Key facts

Study ID

NCT03942328

Run by

Mayo Clinic

People needed

85

Starts

2019-09-19

Expected to finish

2031-02-28

Last updated by the study team

2026-07-10

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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)

You may not qualify if…

• Any of the following because this study involves an investigational agent, the genotoxic, mutagenic and teratogenic effects of which on the developing fetus and newborn are unknown:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential who are unwilling to employ highly effective contraception during heterosexual intercourse while on this study and for 5 months after the last dose of study medication
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Immunocompromised patients and patients known to be HIV positive.
• NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial if they are stable on anti-retroviral therapy, have a CD4+ T cell count ≥ 200/uL, and have an undetectable viral load
• Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection requiring systemic treatment or that could impact patient safety
• Severe infection ≤ 4 weeks prior to registration, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
• Significant cardiovascular disease (New York Heart Association [NYHA] class II), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
• Or, psychiatric illness/social situations (e.g., substance abuse) that would limit compliance with study requirements
• Receiving any other investigational agent that would be considered a treatment for the primary neoplasm
• Other active malignancy =< 1 year prior to registration that is considered by the investigator to interfere with the current treatment or measurement of outcomes
• Major surgery =< 4 weeks prior to enrollment (other than diagnostic surgery or surgical spacer placement in preparation for radiation treatment), or anticipation of need for a major surgical procedure during the study
• History of hypersensitivity or anaphylactoid reactions to pneumococcal vaccine or any component of the formulation, including diphtheria toxoid
• Active or history of autoimmune disease or immune deficiency, including but not limited to,myasthenia gravis, myositis, autoimmune hepatitis, Crohn's disease, inflammatory bowel disease, antiphospholipid antibody syndrome, rheumatoid arthritis, Sjogren syndrome, systemic lupus erythematosus, Guillain-Barre syndrome, multiple sclerosis, Wegener granulomatosis, or similar conditions
• NOTE: Exceptions are allowed for:
• Patients with hypothyroidism on thyroid replacement therapy
• Patients with type 1 diabetes mellitus on insulin regimen
• Patients with eczema, psoriasis lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of the following conditions are met:
• Rash must cover < 10% of body surface area
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids
• There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids ≤ 12 months prior to registration
• Requires anticoagulant treatment (INR > 1.5 x ULN) or use of anti-platelet agents that cannot be discontinued for the intratumoral injection procedure

Where it is running

• Mayo Clinic in Rochester — Rochester, Minnesota, United States (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.