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

NCT03942328 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: MC1641R01CA274985R01CA29470416-009335
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Stage III Intrahepatic Cholangiocarcinoma AJCC v8; Stage IV Hepatocellular Carcinoma AJCC v8; Stage III Hepatocellular Carcinoma AJCC v8; Stage IV Intrahepatic Cholangiocarcinoma AJCC v8; Unresectable Hepatocellular Carcinoma; Unresectable Intrahepatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (3)

• 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.

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

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

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

  At 2 years

• PFS (Phase II Group 3)

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

  Up to 5 years

Secondary Outcomes (7)

• Overall response rate

  Up to 1 year post treatment

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

  Up to 1 year post treatment

• Clinical benefit rate

  Up to 1 year post treatment

• Time to response

  Up to 1 year post treatment

• Duration of response

  Up to 1 year post treatment

Other Outcomes (2)

• Change in target lesion measurements

  Baseline up to 1 year post treatment

• Change in immunologic correlates before and after vaccination treatment

  Baseline up to 1 year post treatment

Study Arms (3)

Phase II Group 2 (EBRT, dendritic cells, Prevnar, atezo, bev)

EXPERIMENTAL

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.

Biological: Atezolizumab; Biological: Bevacizumab; Radiation: External Beam Radiation Therapy; Procedure: Pheresis; Biological: Pneumococcal 13-valent Conjugate Vaccine; Biological: Therapeutic Autologous Dendritic Cells; Procedure: Esophagogastroduodenoscopy; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection

Pilot study (pheresis, EBRT, dendritic cells, Prevnar)

EXPERIMENTAL

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)

Radiation: External Beam Radiation Therapy; Procedure: Pheresis; Biological: Pneumococcal 13-valent Conjugate Vaccine; Biological: Therapeutic Autologous Dendritic Cells

Phase II Group 3 (EBRT, dendritic cells, Prevnar, atezo, tir)

EXPERIMENTAL

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.

Biological: Atezolizumab; Radiation: External Beam Radiation Therapy; Procedure: Pheresis; Biological: Pneumococcal 13-valent Conjugate Vaccine; Biological: Therapeutic Autologous Dendritic Cells; Biological: Durvalumab; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection

Interventions

Atezolizumab BIOLOGICAL

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Phase II Group 2 (EBRT, dendritic cells, Prevnar, atezo, bev); Phase II Group 3 (EBRT, dendritic cells, Prevnar, atezo, tir)

Bevacizumab BIOLOGICAL

Given IV

Also known as: ABP 215, Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF Monoclonal Antibody SIBP04, Anti-VEGF rhuMAb, Avastin, Bevacizumab awwb, Bevacizumab Biosimilar ABP 215, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar GB-222, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar Mvasi, Bevacizumab Biosimilar MYL-1402O, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar QL1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, Bevacizumab Biosimilar Zirabev, Bevacizumab-awwb, Bevacizumab-bvzr, BP102, BP102 Biosimilar, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Mvasi, MYL-1402O, QL1101, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501, SIBP 04, SIBP-04, SIBP04, Zirabev, Alymsys, Avzivi, Aybintio, Onbevzi, Oyavas, Vegzelma

Phase II Group 2 (EBRT, dendritic cells, Prevnar, atezo, bev)

Pheresis PROCEDURE

Undergo apheresis

Also known as: Apheresed, Apheresis, Blood Component Removal, Collection, Apheresis/Leukapheresis, Hemapheresis

Phase II Group 2 (EBRT, dendritic cells, Prevnar, atezo, bev); Phase II Group 3 (EBRT, dendritic cells, Prevnar, atezo, tir); Pilot study (pheresis, EBRT, dendritic cells, Prevnar)

Pneumococcal 13-valent Conjugate Vaccine BIOLOGICAL

Given IM

Also known as: PCV 13, PCV13 Vaccine, Prevnar 13

Phase II Group 2 (EBRT, dendritic cells, Prevnar, atezo, bev); Phase II Group 3 (EBRT, dendritic cells, Prevnar, atezo, tir); Pilot study (pheresis, EBRT, dendritic cells, Prevnar)

Therapeutic Autologous Dendritic Cells BIOLOGICAL

Given IT

Phase II Group 2 (EBRT, dendritic cells, Prevnar, atezo, bev); Phase II Group 3 (EBRT, dendritic cells, Prevnar, atezo, tir); Pilot study (pheresis, EBRT, dendritic cells, Prevnar)

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, MEDI 4736, MEDI-4736, MEDI4736

Phase II Group 3 (EBRT, dendritic cells, Prevnar, atezo, tir)

Esophagogastroduodenoscopy PROCEDURE

Undergo EGD

Also known as: EGD, Upper Endoscopy

Phase II Group 2 (EBRT, dendritic cells, Prevnar, atezo, bev)

Computed Tomography PROCEDURE

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, computerized axial tomography, computerized tomography, Computerized Tomography (CT) scan, CT, CT SCAN, Diagnostic CAT Scan

Phase II Group 2 (EBRT, dendritic cells, Prevnar, atezo, bev); Phase II Group 3 (EBRT, dendritic cells, Prevnar, atezo, tir)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, positron emission tomography scan, PT

Phase II Group 2 (EBRT, dendritic cells, Prevnar, atezo, bev); Phase II Group 3 (EBRT, dendritic cells, Prevnar, atezo, tir)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: MRI, Magnetic Resonance Imaging (MRI), Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Phase II Group 2 (EBRT, dendritic cells, Prevnar, atezo, bev); Phase II Group 3 (EBRT, dendritic cells, Prevnar, atezo, tir)

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: BIOPSY, Bx

Phase II Group 2 (EBRT, dendritic cells, Prevnar, atezo, bev); Phase II Group 3 (EBRT, dendritic cells, Prevnar, atezo, tir)

Biospecimen Collection PROCEDURE

Undergo urine and blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Phase II Group 2 (EBRT, dendritic cells, Prevnar, atezo, bev); Phase II Group 3 (EBRT, dendritic cells, Prevnar, atezo, tir)

External Beam Radiation Therapy RADIATION

Undergo high-dose EBRT

Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy, External Beam Radiotherapy (conventional), External Beam RT, external radiation, External Radiation Therapy, external-beam radiation, Radiation, External Beam, Teleradiotherapy, Teletherapy, Teletherapy Radiation

Phase II Group 2 (EBRT, dendritic cells, Prevnar, atezo, bev); Phase II Group 3 (EBRT, dendritic cells, Prevnar, atezo, tir); Pilot study (pheresis, EBRT, dendritic cells, Prevnar)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Cholangiocarcinoma

Interventions

atezolizumab; Bevacizumab; Immunoglobulin G; Disulfides; Congresses as Topic; Radiation; Blood Component Removal; 13-valent pneumococcal vaccine; durvalumab; Endoscopy, Digestive System; Gastroscopy; Magnetic Resonance Spectroscopy; Biopsy; Specimen Handling

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Organizations; Health Care Economics and Organizations; Physical Phenomena; Therapeutics; Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Endoscopy, Gastrointestinal; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques

Study Officials

• Lewis R. Roberts, MD, PhD

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

• Lionel Kankeu Fonkoua, MD

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2019
• First Posted: May 8, 2019
• Study Start: September 19, 2019
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): August 31, 2029
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (1)