Modified Immune Cells (Autologous Dendritic Cells) and a Vaccine (Prevnar) After High-Dose External Beam Radiation Therapy in Treating Patients With Unresectable Liver Cancer

Unresectable Hepatocellular Carcinoma Clinical Trial

Official title: Study of Intratumoral Injection of Dendritic Cells After High-Dose Conformal External Beam Radiotherapy in Patients With Unresectable Liver Cancer

Status Recruiting

Clinical Trial Summary

This Phase I-II trial studies the safety and efficacy of autologous dendritic cells and a vaccine called Prevnar in treating patients with liver cancer that cannot be removed by surgery after undergoing standard high-dose external beam radiotherapy. Autologous dendritic cells are immune cells generated from the 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. Giving autologous dendritic cells and Prevnar to patients with liver cancer after radiotherapy may help doctors determine if it is possible to stimulate the body's own immune system to fight against the tumor, and to see if this immune stimulation can be done safely (Phase I) and can be combined with immune checkpoint inhibitors (Phase II). The Phase I cohort will only include patients with unresectable intrahepatic cholangiocarcinoma, while the Phase II cohort will only include patients with unresectable hepatocellular carcinoma..

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Evaluation of safety and tolerability of an autologous dendritic cell (DC) vaccine delivered by intra-tumoral injection in patients with unresectable intrahepatic cholangiocarcinoma treated with high-dose conformal external beam radiotherapy (EBRT). (Phase I)

II. Assess the safety and clinical efficacy of an autologous dendritic cell (DC) vaccine delivered by intra-tumoral injection, in combination with intravenous atezolizumab and bevacizumab, in patients with unresectable hepatocellular carcinoma treated with high-dose conformal external beam radiotherapy (EBRT). (Phase II)

SECONDARY OBJECTIVES:

I. To assess feasibility in patients with liver cancer treated with high-dose conformal EBRT followed by autologous DC vaccine injection.

II. To assess overall response rate in patients with liver cancer treated with high-dose conformal EBRT followed by autologous DC vaccine injection.

III. To assess progression free survival in patients with liver cancer treated with high-dose conformal EBRT followed by autologous DC vaccine injection.

IV. To assess clinical benefit rate in patients with liver cancer treated with high-dose conformal EBRT followed by autologous DC vaccine injection.

V. To assess time to response in patients with liver cancer treated with high-dose conformal EBRT followed by autologous DC vaccine injection.

VI. To assess duration of response in patients with liver cancer treated with high-dose conformal EBRT followed by autologous DC vaccine injection.

VII. To assess overall survival in patients with liver cancer treated with high-dose conformal EBRT followed by autologous DC vaccine injection.

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.

CORRELATIVE RESEARCH OBJECTIVES:

I. To monitor patients' immune response after vaccine therapy. II. To assess the immune response to pneumococcal 13-valent conjugate vaccine (Prevnar).

OUTLINE:

PILOT STUDY (GROUP I): 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 hepatocellular carcinoma (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 IM on day 1 of cycles 2-4 only. Patients also receive standard of care atezolizumab intravenously (IV) and bevacizumab 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.

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. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Cholangiocarcinoma
• Liver Neoplasms
• 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

• NCT number: NCT03942328
• Study type: Interventional
• Source: Mayo Clinic
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 19, 2019
• Completion date: February 29, 2028