Health TrialsbyHealthPanel

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

ConditionsStage III Hepatocellular Carcinoma AJCC v8Stage III Intrahepatic Cholangiocarcinoma AJCC v8Stage IV Hepatocellular Carcinoma AJCC v8Stage IV Intrahepatic Cholangiocarcinoma AJCC v8Unresectable Hepatocellular CarcinomaUnresectable Intrahepatic Cholangiocarcinoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMayo Clinic

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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)

Disqualifiers

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

Trial design

Design model

Crossover

Treatments tested in this trial

  • Atezolizumab

    Biological/Vaccine

    Given IV

  • Bevacizumab

    Biological/Vaccine

    Given IV

  • External Beam Radiation Therapy

    Radiation

    Undergo high-dose EBRT

  • Pheresis

    Procedure/Surgery

    Undergo apheresis

  • Pneumococcal 13-valent Conjugate Vaccine

    Biological/Vaccine

    Given IM

  • Therapeutic Autologous Dendritic Cells

    Biological/Vaccine

    Given IT

  • Durvalumab

    Biological/Vaccine

    Given IV

  • Esophagogastroduodenoscopy

    Procedure/Surgery

    Undergo EGD

  • Computed Tomography

    Procedure/Surgery

    Undergo CT or PET/CT

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo PET/CT

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Biopsy Procedure

    Procedure/Surgery

    Undergo biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo urine and blood sample collection

Treatment groups

85 Participants
are divided into 3 treatment groups
Group A: Phase II Group 2 (EBRT, dendritic cells, Prevnar, atezo, bev)Experimental treatment 12 interventions
Group B: Pilot study (pheresis, EBRT, dendritic cells, Prevnar)Experimental treatment 4 interventions
Group C: Phase II Group 3 (EBRT, dendritic cells, Prevnar, atezo, tir)Experimental treatment 11 interventions

Trial outcomes

Primary outcomes

1

Incidence of significant toxicity (Pilot study)

A significant toxicity is defined as a dose limiting toxicity that is possibly, probably, or definitely related to dendritic cell (DC) treatment. Toxicities will be assessed using the Cancer Therapy Evaluation Program active version of the Common Terminology Criteria for Adverse Events.

Time frame
Up to completion of cycle 2 (each cycle is 28 days)
2

Progression-free survival rate at 2 years (Phase II)

Defined as the time from registration to disease progression or death due to all causes.

Time frame
At 2 years
3

PFS (Phase II Group 3)

Defined as the time from registration to disease progression or death due to all causes.

Time frame
Up to 5 years

Secondary outcomes

1

Overall response rate

The overall response rate will be estimated by the number of patients with an objective status of complete response (CR) or partial response (PR) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.

Time frame
Up to 1 year post treatment
2

Number of patients who received at least one dose of intratumoral DC injection

The feasibility of the regimen will be estimated by the number of patients who received at least one dose of intratumoral DC injection divided by the total number of patients who received apheresis.

Time frame
Up to 1 year post treatment
3

Clinical benefit rate

The clinical benefit rate will be estimated by the number of patients with an objective status of stable disease or CR or PR at any time divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true clinical benefit rate will be calculate

Time frame
Up to 1 year post treatment
4

Time to response

Time to response is defined for all evaluable patients who have achieved an objective response as the date of initiation of vaccination treatment to the date at which the patient's objective status is first noted to be either a CR or PR. Time to response will be summarized descriptively using Kaplan-Meier methodology.

Time frame
Up to 1 year post treatment

Other outcomes

1

Change in target lesion measurements

All enhancing lesions will be evaluated over time for each patient. The percent change from baseline in target lesion measurements will be assessed over time. Differences in values over time will be summarized descriptively and graphically.

Time frame
Baseline up to 1 year post treatment
2

Change in immunologic correlates before and after vaccination treatment

Change in immunologic correlates before and after vaccination treatment will be evaluated and summarized both quantitatively and graphically. Each of the correlative endpoints will be summarized individually, but will also be evaluated in terms of their relationships to one another; i.e., will use Spearman rank correlation coefficient to assess the correlations between baseline levels as well as between changes before and after treatment in these immunologic markers. In addition, these immunologic markers will be correlated with cancer and treatment related outcomes (e.g. response, adverse events). Relationships will also be explored graphically using scatter plots.

Time frame
Baseline up to 1 year post treatment

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Mayo Clinic

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
Apply now