Immunotherapy + Vaccine for Liver Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Mayo Clinic

Must not be taking: Antiretrovirals, Corticosteroids

Disqualifiers: Pregnancy, Immunocompromised, Autoimmune diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 21-28 days per cycle, up to 7 cycles

54 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on corticosteroids, you may need to adjust your dosage to less than 10 mg/day of prednisone (or equivalent) to participate.

What data supports the effectiveness of this treatment for liver cancer?

Research shows that combining radiation therapy with dendritic cell injections can enhance the immune response against tumors. In a study with liver cancer patients, this combination was safe and led to some tumor shrinkage and improved immune activity, suggesting potential effectiveness. ^{1 2 3 4 5}

Is the combination of immunotherapy and external beam radiation therapy generally safe for humans?

External beam radiation therapy (EBRT) is considered safe and is used as a treatment for various conditions, including liver cancer and soft tissue sarcoma. Studies have shown that combining EBRT with dendritic cell injections is being explored for its potential to enhance immune responses against tumors. ^{4 5 6 7 8}

How is the Immunotherapy + Vaccine treatment for liver cancer different from other treatments?

This treatment is unique because it combines external beam radiation therapy (EBRT) with the injection of dendritic cells (a type of immune cell) directly into the tumor, aiming to boost the body's immune response against the cancer. This approach is different from standard treatments as it not only targets the tumor directly with radiation but also enhances the immune system's ability to fight the cancer. ^{4 5 6 8 9}

What is the purpose of this trial?

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..

Research Team

Lewis R. Roberts, MD, PhD

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

This trial is for adults with liver cancer that can't be removed by surgery. They must have a certain level of white blood cells, kidney function, and liver function, and not be pregnant or nursing. People with other active cancers, recent major surgeries, severe allergies to vaccines, HIV on antiretroviral therapy, serious illnesses that could affect the study results or who are taking certain medications are excluded.

Inclusion Criteria

My urine protein levels are low enough for the trial.

My liver cancer has been confirmed by tests and scans.

Prothrombin time/international normalized ratio (PT/ INR) =< 1.5 x ULN (obtained =< 14 days prior to registration)

Exclusion Criteria

My liver cancer is in the most advanced stage.

- Nursing persons

My liver disease is moderately to severely advanced.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Patients undergo high-dose conformal external beam radiotherapy (EBRT) for 5 or 15 fractions over 1-3 weeks

1-3 weeks

Treatment

Patients receive autologous dendritic cells intratumorally and pneumococcal 13-valent conjugate vaccine intramuscularly. In Phase II, patients also receive atezolizumab and bevacizumab intravenously.

21-28 days per cycle, up to 7 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups at 2 weeks, then every 3 months for 1 year, and every 6 months until 5 years after registration.

5 years

Treatment Details

Interventions

• External Beam Radiation Therapy
• Pneumococcal 13-valent Conjugate Vaccine
• Therapeutic Autologous Dendritic Cells

Trial Overview The trial tests if modified immune cells (autologous dendritic cells) from patients' own blood can stimulate the immune system to fight liver cancer when given after high-dose radiation therapy. It also examines whether adding Prevnar vaccine enhances this effect. The safety and effectiveness of combining these treatments with immune checkpoint inhibitors will be studied in two phases for different types of liver cancer.

Participant Groups

Group I: Pilot study (pheresis, EBRT, dendritic cells, Prevnar) Experimental Treatment 4 Interventions

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.

Group II: Phase II(pheresis, EBRT, dendritic cells, Prevnar, atezo, bev) Experimental Treatment 6 Interventions

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 IM on day 1 of cycles 2-4 only. Patients also receive standard of care atezolizumab 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.

External Beam Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in United States as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in Canada as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in Japan as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in China as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in Switzerland as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The study evaluated the safety and efficacy of a dendritic cell (DC) vaccine in 20 Egyptian patients with advanced hepatocellular carcinoma (HCC), showing that the DC vaccine had minimal adverse effects and no autoimmunity, indicating it is safe for use.

Patients receiving the DC vaccine demonstrated a partial response and stable disease rates, while those on supportive treatment experienced 100% progressive disease, suggesting potential benefits of the DC vaccine, although further research with a larger cohort is needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous dendritic cells pulsed with lysate from an allogeneic hepatic cancer cell line as a treatment for patients with advanced hepatocellular carcinoma: A pilot study. Abdel Ghafar, MT., Morad, MA., El-Zamarany, EA., et al.[2020]

The autologous dendritic cell vaccine (DC-ATA) has shown promising results in over 200 patients with various cancers, demonstrating a well-tolerated treatment with a rapid immune response primarily involving TH1/TH17 cells.

Clinical trials indicate that DC-ATA may lead to durable tumor regressions and improved survival rates, particularly in metastatic melanoma and glioblastoma, suggesting its potential as an effective immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous dendritic cells loaded with antigens from self-renewing autologous tumor cells as patient-specific therapeutic cancer vaccines. Dillman, RO., Nistor, GI., Keirstead, HS.[2023]

The phase 1 study involving 14 advanced hepatoma patients demonstrated that direct injection of autologous immature dendritic cells (DCs) combined with radiotherapy is safe, with only mild side effects reported, such as transient fever and fatigue.

The treatment induced a tumor-specific immune response, evidenced by a significant decrease in alpha-fetoprotein (AFP) levels in some patients and increased natural killer (NK) cell activity, suggesting potential efficacy in combating the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of conformal radiotherapy and intratumoral injection of adoptive dendritic cell immunotherapy in refractory hepatoma. Chi, KH., Liu, SJ., Li, CP., et al.[2022]

The combination of intratumoral dendritic cell (DC) administration and fractionated external beam radiation therapy (EBRT) was safe and well tolerated in 17 patients with large high-grade soft-tissue sarcoma, leading to the development of tumor-specific immune responses in 52.9% of patients.

After one year, 70.6% of patients remained progression-free, indicating that this treatment approach not only induced immune responses but also had potential long-term benefits in controlling tumor growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of external beam radiotherapy (EBRT) with intratumoral injection of dendritic cells as neo-adjuvant treatment of high-risk soft tissue sarcoma patients. Finkelstein, SE., Iclozan, C., Bui, MM., et al.[2021]

Combining local radiotherapy with intratumoral injections of dendritic cells (DC) shows promise in enhancing the immune response against tumors, as suggested by preclinical studies in mouse models.

A pilot study involving 5 patients with high-risk prostate cancer demonstrated that this combination therapy, alongside radiation treatment, could potentially improve immune activity against cancer, indicating a new avenue for cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical opportunities in combining immunotherapy with radiation therapy. Finkelstein, SE., Fishman, M.[2021]

External beam radiation therapy (EBRT) is an effective palliative treatment for patients with hepatocellular carcinoma (HCC) and bone metastases, showing a median overall survival of 6 months and a one-year overall survival rate of 23.1% based on a review of 19 studies involving 1613 patients.

EBRT significantly reduces pain in these patients, with an 81.5% response rate and a 26.5% rate of complete pain remission, although careful monitoring for hematologic complications is necessary, as they occurred in 11.5% to 34% of cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy for bone metastases of hepatocellular carcinoma: a hybrid systematic review with meta-analyses. Rim, CH., Park, S., Yoon, WS., et al.[2023]

External beam radiation therapy (EBRT) is used as a bridging therapy for liver transplant in patients with hepatocellular carcinoma (HCC), but it is only utilized in 3.5% of patients, indicating a significant gap in treatment options compared to other liver-directed therapies.

The use of EBRT has been increasing at an average rate of 12.2% per year, and it is associated with a 30% increased risk of receiving a liver transplant, although it does not significantly affect the risk of waitlist removal due to clinical deterioration or death.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Utilization of External Beam Radiation Therapy for Patients With Unresectable Hepatocellular Carcinoma: An Analysis of the United Network for Organ Sharing Database. Herman, T., Kaempf, A., Schlansky, B., et al.[2022]

External beam radiotherapy (EBRT) has been shown to improve survival rates in patients with intermediate to advanced hepatocellular carcinoma (HCC), particularly those with portal vein or inferior vena cava tumor thrombi, extending survival to an average of 10.7 months.

When compared to sorafenib, a commonly recommended treatment for HCC, EBRT demonstrated superior effectiveness in improving patient survival for tumors of similar metastatic size, suggesting it should be considered in treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is it time to adopt external beam radiotherapy in the NCCN guidelines as a therapeutic strategy for intermediate/advanced hepatocellular carcinoma?. Jiang, W., Zeng, ZC.[2018]

External beam radiotherapy (EBRT) after incomplete transarterial chemoembolization (TACE) in 40 patients with hepatocellular carcinoma showed promising oncologic outcomes, with 1-year overall survival at 82.2% and local control rates at 89.1%.

Despite the favorable outcomes, intrahepatic recurrence was the main cause of disease progression, highlighting the need for improved strategies to manage this issue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of external beam radiotherapy complementing incomplete transarterial chemoembolization for hepatocellular carcinoma. Park, S., Yoon, WS., Jang, MH., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Autologous dendritic cells pulsed with lysate from an allogeneic hepatic cancer cell line as a treatment for patients with advanced hepatocellular carcinoma: A pilot study. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Autologous dendritic cells loaded with antigens from self-renewing autologous tumor cells as patient-specific therapeutic cancer vaccines. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Combination of conformal radiotherapy and intratumoral injection of adoptive dendritic cell immunotherapy in refractory hepatoma. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Combination of external beam radiotherapy (EBRT) with intratumoral injection of dendritic cells as neo-adjuvant treatment of high-risk soft tissue sarcoma patients. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical opportunities in combining immunotherapy with radiation therapy. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Radiotherapy for bone metastases of hepatocellular carcinoma: a hybrid systematic review with meta-analyses. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Low Utilization of External Beam Radiation Therapy for Patients With Unresectable Hepatocellular Carcinoma: An Analysis of the United Network for Organ Sharing Database. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Is it time to adopt external beam radiotherapy in the NCCN guidelines as a therapeutic strategy for intermediate/advanced hepatocellular carcinoma?. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Clinical efficacy of external beam radiotherapy complementing incomplete transarterial chemoembolization for hepatocellular carcinoma. [2021]