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

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 tiragolumab IV over 30-60 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 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.