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RecruitingNCT03942328

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

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

Status
Recruiting
Phase
Phase 1 / Phase 2
Study type
Interventional
Enrollment
85 (estimated)
Sponsor
Mayo Clinic · Academic / Other
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

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.

Detailed description

PRIMARY OBJECTIVE: I. Evaluation of safety and tolerability of an autologous dendritic cell (DC) vaccine delivered by intra-tumoral injection in patients with primary liver cancer treated with high-dose conformal external beam radiotherapy (EBRT). (Pilot Study) II. Estimate the progression-free survival rate at 2 years post-registration to see if treatment is efficacious compared to historical data in hepatocellular carcinoma (HCC). (Phase II Group 2) II. Estimate the progression-free survival to see if treatment is efficacious compared to historical data in intrahepatic cholangiocarcinoma (iCCA) patients. (Phase II Group 3) SECONDARY OBJECTIVES: I. To assess feasibility in patients with liver cancer treated with high-dose conformal EBRT followed by autologous DC vaccine injection by group (Group 1 versus \[vs.\] 2 vs. 3). II. To assess overall response rate in patients with liver cancer treated with high-dose conformal EBRT followed by autologous DC vaccine injection by group (Group 1 vs. 2 vs. 3). III. To assess progression free survival in patients with liver cancer treated with high-dose conformal EBRT followed by autologous DC vaccine injection by group (Group 1 vs. 2 vs. 3). IV. To assess clinical benefit rate in patients with liver cancer treated with high-dose conformal EBRT followed by autologous DC vaccine injection by group (Group 1 vs. 2 vs. 3). V. To assess time to response in patients with liver cancer treated with high-dose conformal EBRT followed by autologous DC vaccine injection by group (Group 1 vs. 2 vs. 3). VI. To assess duration of response in patients with liver cancer treated with high-dose conformal EBRT followed by autologous DC vaccine injection by group (Group 1 vs. 2 vs. 3). VII. To assess overall survival in patients with liver cancer treated with high-dose conformal EBRT followed by autologous DC vaccine injection by group (Group 1 vs. 2 vs. 3). RADIOLOGIC STUDY OBJECTIVE: I. To assess the radiologic response over time of primary liver tumors treated with high-dose conformal EBRT followed by autologous DC vaccine injection by group (Group 1 vs. 2 vs. 3). CORRELATIVE RESEARCH OBJECTIVES: I. To monitor patients' immune response after vaccine therapy by group (Group 1 vs. 2 vs. 3). II. To assess the immune response to pneumococcal 13-valent conjugate vaccine (Prevnar) and similar pneumococcal vaccines by group (Group 1 vs. 2 vs. 3). OUTLINE: PILOT STUDY (GROUP I) (CLOSED WITH AMENDMENT 3): Patients with unresectable intrahepatic cholangiocarcinoma (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 intratumorally (IT) on day 1 of cycles 2-8 and pneumococcal 13-valent conjugate vaccine intramuscularly (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. PHASE II STUDY (GROUP II): 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 intravenously (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 esophagogastroduodenoscopy (EGD) at screening and CT, PET/CT and/or MRI, biopsy and urine and blood sample collection throughout the study. PHASE II STUDY (GROUP III): 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 atezolizumab IV over 30-60 minutes and 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. After completion of study treatment, patients are followed up at 2 weeks and then every 3 months for 1 year (beginning at week 36 or 12 weeks after last autologous dendritic cell dose whichever is earlier). Patients are then followed every 3 months until disease progression, and then every 6 months until 5 years after registration.

Conditions

Interventions

TypeNameDescription
BIOLOGICALAtezolizumabGiven IV
BIOLOGICALBevacizumabGiven IV
RADIATIONExternal Beam Radiation TherapyUndergo high-dose EBRT
PROCEDUREPheresisUndergo apheresis
BIOLOGICALPneumococcal 13-valent Conjugate VaccineGiven IM
BIOLOGICALTherapeutic Autologous Dendritic CellsGiven IT
BIOLOGICALDurvalumabGiven IV
PROCEDUREEsophagogastroduodenoscopyUndergo EGD
PROCEDUREComputed TomographyUndergo CT or PET/CT
PROCEDUREPositron Emission TomographyUndergo PET/CT
PROCEDUREMagnetic Resonance ImagingUndergo MRI
PROCEDUREBiopsy ProcedureUndergo biopsy
PROCEDUREBiospecimen CollectionUndergo urine and blood sample collection

Timeline

Start date
2019-09-19
Primary completion
2027-08-31
Completion
2028-02-29
First posted
2019-05-08
Last updated
2026-02-24

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT03942328. Inclusion in this directory is not an endorsement.