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

Part of paid clinical trials in Rochester, Minnesota.

Sponsor
Mayo Clinic
Study ID
NCT03942328
Phase
PHASE1/PHASE2
Status
Recruiting
Apply to this trial

Conditions

  • 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

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Atezolizumab — BIOLOGICAL
    Given IV
  • Bevacizumab — BIOLOGICAL
    Given IV
  • External Beam Radiation Therapy — RADIATION
    Undergo high-dose EBRT
  • Pheresis — PROCEDURE
    Undergo apheresis
  • Pneumococcal 13-valent Conjugate Vaccine — BIOLOGICAL
    Given IM
  • Therapeutic Autologous Dendritic Cells — BIOLOGICAL
    Given IT
  • Durvalumab — BIOLOGICAL
    Given IV
  • Esophagogastroduodenoscopy — PROCEDURE
    Undergo EGD
  • Computed Tomography — PROCEDURE
    Undergo CT or PET/CT
  • Positron Emission Tomography — PROCEDURE
    Undergo PET/CT
  • Magnetic Resonance Imaging — PROCEDURE
    Undergo MRI
  • Biopsy Procedure — PROCEDURE
    Undergo biopsy
  • Biospecimen Collection — PROCEDURE
    Undergo urine and blood sample collection

Study Details

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 Dates

Start date
Sep 19, 2019
Status verified
Apr 2026
Primary completion
Aug 31, 2029
Completion
Aug 31, 2029

Study Design

Enrollment
85 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT

Arms

  • Experimental: Phase II Group 2 (EBRT, dendritic cells, Prevnar, atezo, bev)
    Patients with unresectable HCC undergo apheresis for dendric cell manufacturing and standard of care high-dose EBRT for 5 or 15 fractions over 1-3 weeks (cycle 1). Patients then receive autologous dendritic cells IT on day 1 of cycles 2-8 and pneumococcal 13-valent conjugate vaccine or other pneumococcal vaccine IM on day 1 of cycles 2-4 only. Patients also receive standard of care atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes starting on day 2 of cycles 2-8. Treatment repeats every 21 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo an EGD at screening and CT, PET/CT and/or MRI, biopsy and urine and blood sample collection throughout the study.
  • Experimental: Pilot study (pheresis, EBRT, dendritic cells, Prevnar)
    Patients with unresectable intrahepatic CCA undergo apheresis for dendric cell manufacturing and standard of care high-dose EBRT for 5 or 15 fractions over 1-3 weeks (cycle 1). Patients then receive autologous dendritic cells IT on day 1 of cycles 2-8 and pneumococcal 13-valent conjugate vaccine IM on day 1 of cycles 2-4 only. Treatment repeats every 28 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity. (CLOSED WITH AMENDMENT 3)
  • Experimental: Phase II Group 3 (EBRT, dendritic cells, Prevnar, atezo, tir)
    Patients with iCCA undergo apheresis for dendric cell manufacturing and standard of care high-dose EBRT for 5 or 15 fractions over 1-3 weeks (cycle 1). Patients then receive autologous dendritic cells IT on day 1 of cycles 2-8 and pneumococcal 13-valent conjugate vaccine or other pneumococcal vaccine IM on day 1 of cycles 2-4 only. Patients also receive standard of care durvalumab IV starting on day 2 of cycles 2-8. Treatment repeats every 21 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT, PET/CT and/or MRI, biopsy and urine and blood sample collection throughout the study.

Primary Outcome Measure

Incidence of significant toxicity (Pilot study) [ Time Frame: Up to completion of cycle 2 (each cycle is 28 days) ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Mayo Clinic in RochesterRochesterMinnesota55905
Clinical Trials Referral Office
[email protected]
855-776-0015
Lewis R. Roberts, MD, PhD (PRINCIPAL_INVESTIGATOR)
Lionel Kankeu Fonkoua, MD (PRINCIPAL_INVESTIGATOR)

Find similar trials in Rochester, MN

By condition
Liver cancer
By specialty
OncologyGI oncologyHepatology
By research site
Mayo Clinic in Rochester· Rochester, MN

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