Immunotherapy + Vaccine for Liver Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Mayo Clinic
Must not be taking: Antiretrovirals, Corticosteroids
Disqualifiers: Pregnancy, Immunocompromised, Autoimmune diseases, others
No Placebo Group
Breakthrough Therapy
Trial Summary
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..
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.
12345Is 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.
45678How 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.
45689Eligibility 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)
+24 more
Exclusion Criteria
My liver cancer is in the most advanced stage.
- Nursing persons
My liver disease is moderately to severely advanced.
+21 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Pilot study (pheresis, EBRT, dendritic cells, Prevnar)Experimental Treatment4 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 Treatment6 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mayo Clinic in RochesterRochester, MN
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Who Is Running the Clinical Trial?
Mayo ClinicLead Sponsor
National Cancer Institute (NCI)Collaborator
References
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]This is a randomized trial adopted to evaluate the safety and efficacy of immunization with specific anti-hepatocellular carcinoma dendritic cells (DCs) in Egyptian patients with advanced hepatocellular carcinoma (HCC) as a treatment or adjuvant therapy in comparison with the traditional therapy.
Autologous dendritic cells loaded with antigens from self-renewing autologous tumor cells as patient-specific therapeutic cancer vaccines. [2023]A promising personal immunotherapy is autologous dendritic cells (DC) loaded ex vivo with autologous tumor antigens (ATA) derived from self-renewing autologous cancer cells. DC-ATA are suspended in granulocyte-macrophage colony stimulating factor at the time of each subcutaneous injection. Previously, irradiated autologous tumor cell vaccines have produced encouraging results in 150 cancer patients, but the DC-ATA vaccine demonstrated superiority in single-arm and randomized trials in metastatic melanoma. DC-ATA have been injected into more than 200 patients with melanoma, glioblastoma, and ovarian, hepatocellular, and renal cell cancers. Key observations include: [1] greater than 95% success rates for tumor cell cultures and monocyte collection for dendritic cell production; [2] injections are well-tolerated; [3] the immune response is rapid and includes primarily TH1/TH17 cellular responses; [4] efficacy has been suggested by delayed but durable complete tumor regressions in patients with measurable disease, by progression-free survival in glioblastoma, and by overall survival in melanoma.
Combination of conformal radiotherapy and intratumoral injection of adoptive dendritic cell immunotherapy in refractory hepatoma. [2022]A phase 1 study was conducted to assess the safety and immunologic response induced by direct injection of autologous immature dendritic cells (DCs) into tumor under radiotherapy in advanced hepatoma patients. Patients with advanced/metastatic stage hepatoma not suitable for surgery or transarterial embolization were enrolled. Groups of patients received two vaccinations. Each vaccination consisted of intratumoral injections of autologous immature DCs in four dose cohorts of 5 x 10(6), 1.5 x 10(7), 3 x 10(7), and 5 x 10(7) cells 2 days after a single fraction of conformal radiotherapy of 8 Gy. The second vaccination was performed 3 weeks later. Of the 14 patients entered, 12 completed two cycles of vaccination. The treatment was well tolerated at any of the dose levels. Six patients had mild transient fever (grade 1-2) with chill reactions, three patients developed grade 1 fatigue, and one patient developed mild myalgia and arthralgia after DC injections. There was no evidence of clinically manifested autoimmune disease. There were two partial responses and four minor responses. A decrease in the alpha-fetoprotein (AFP) level of more than 50% was found in three patients. Ten patients had completed immunologic response evaluation 2 weeks after the second cycle of vaccination. The AFP-specific immune response was evident in eight patients examined by cytokine release assay and in seven patients by ELISPOT assay. Six patients showed an increased NK cell cytotoxic activity after vaccination. These data suggest that the combination of intratumoral injection of DCs and conformal radiotherapy is safe and can induce tumor-specific and innate immunity.
Combination of external beam radiotherapy (EBRT) with intratumoral injection of dendritic cells as neo-adjuvant treatment of high-risk soft tissue sarcoma patients. [2021]The goal of this study was to determine the effect of combination of intratumoral administration of dendritic cells (DC) and fractionated external beam radiation (EBRT) on tumor-specific immune responses in patients with soft-tissue sarcoma (STS).
Clinical opportunities in combining immunotherapy with radiation therapy. [2021]Preclinical work in murine models suggests that local radiotherapy plus intratumoral syngeneic dendritic cells (DC) injection can mediate immunologic tumor eradication. Radiotherapy affects the immune response to cancer, besides the direct impact on the tumor cells, and other ways to coordinate immune modulation with radiotherapy have been explored. We review here the potential for immune-mediated anticancer activity of radiation on tumors. This can be mediated by differential antigen acquisition and presentation by DC, through changes of lymphocytes' activation, and changes of tumor susceptibility to immune clearance. Recent work has implemented the combination of external beam radiation therapy (EBRT) with intratumoral injection of DC. This included a pilot study of coordinated intraprostatic, autologous DC injection together with radiation therapy with five HLA-A2(+) subjects with high-risk, localized prostate cancer; the protocol used androgen suppression, EBRT (25 fractions, 45 Gy), DC injections after fractions 5, 15, and 25, and then interstitial radioactive implant. Another was a phase II trial using neo-adjuvant apoptosis-inducing EBRT plus intra-tumoral DC in soft tissue sarcoma, to test if this would increase immune activity toward soft tissue sarcoma associated antigens. In the future, radiation therapy approaches designed to optimize immune stimulation at the level of DC, lymphocytes, tumor and stroma effects could be evaluated specifically in clinical trials.
Radiotherapy for bone metastases of hepatocellular carcinoma: a hybrid systematic review with meta-analyses. [2023]External beam radiation therapy (EBRT) is commonly used as a palliative treatment for bone metastases of hepatocellular carcinoma (HCC). We planned a hybrid systematic review that meta-analyzed the efficacy and feasibility of EBRT and reviewed the literature to answer specific clinical questions.
Low Utilization of External Beam Radiation Therapy for Patients With Unresectable Hepatocellular Carcinoma: An Analysis of the United Network for Organ Sharing Database. [2022]External beam radiation therapy (EBRT) is a safe and emerging bridging liver-directed therapy (LDT) to liver transplant (LT) for patients with hepatocellular carcinoma (HCC). The prevalence and clinical characteristics of patients receiving EBRT as an LDT for LT have not been evaluated. Our aim was to describe the utilization of EBRT in patients with HCC evaluated for LT in the United States.
Is it time to adopt external beam radiotherapy in the NCCN guidelines as a therapeutic strategy for intermediate/advanced hepatocellular carcinoma?. [2018]External beam radiotherapy (EBRT) is recommended as a therapeutic strategy for stage III hepatocellular carcinoma (HCC) in national guidelines of the Chinese Society of Liver Disease and in Korea Liver Cancer Study Group practice guidelines, but has not been considered a therapeutic option for HCC in Western countries. In this study, we review evidence supporting EBRT as an option for HCC treatment.
Clinical efficacy of external beam radiotherapy complementing incomplete transarterial chemoembolization for hepatocellular carcinoma. [2021]External beam radiotherapy (EBRT) has been commonly applied as salvage or a combination locoregional modality after transarterial chemoembolization (TACE) for hepatocellular carcinomas (HCCs). This study reports oncologic outcomes and feasibility after application of the two modalities in our center.