What side effects are associated with this type of intervention?

Common treatments for liver cancer, particularly those involving immunotherapy and targeted therapies like Anti-GPC3 CAR-T cells, often have side effects related to immune system activation. These can include cytokine release syndrome (CRS), which manifests as fever, fatigue, and low blood pressure, and immune effector cell-associated neurotoxicity syndrome (ICANS), which can cause confusion, seizures, and headaches. Other side effects may include liver toxicity, leading to elevated liver enzymes, and general symptoms such as nausea, fatigue, and infections due to immunosuppression.

What prior FDA approvals exist?

FDA-approved treatments for liver cancer include targeted therapies and immunotherapies. Sorafenib and lenvatinib are kinase inhibitors that have been approved for advanced hepatocellular carcinoma (HCC). Additionally, the combination of atezolizumab (an anti-PD-L1 antibody) and bevacizumab (an anti-VEGF antibody) has been approved for unresectable HCC. While these treatments do not involve genetically modified T cells like Anti-GPC3 CAR-T cells, they represent significant advancements in targeted and immune-based therapies for liver cancer.

What other types of research exist?

Promising novel alternatives to Anti-GPC3 CAR-T cells for liver cancer patients include: 1) Immune checkpoint inhibitors such as pembrolizumab and nivolumab, which have shown efficacy in various liver cancer subtypes. 2) Combination therapies like atezolizumab plus bevacizumab, which have demonstrated improved survival outcomes. 3) Targeted therapies such as lenvatinib and sorafenib, which are effective in advanced hepatocellular carcinoma. These options provide a range of mechanisms to target liver cancer cells and improve patient outcomes.

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CAR T-cell Therapy

CAR-T Cell Therapy for Liver Cancer

Q: What is the mechanism of action of this treatment?

Common treatments for liver cancer include targeted therapies, immunotherapies, and chemotherapy. Targeted therapies, such as sorafenib and lenvatinib, inhibit specific molecules involved in tumor growth and angiogenesis. Immunotherapies, like Anti-GPC3 CAR-T cells, involve modifying a patient's T cells to target and destroy cancer cells expressing specific antigens like GPC3. Chemotherapy uses cytotoxic drugs to kill rapidly dividing cancer cells. These mechanisms are crucial for liver cancer patients as they offer personalized treatment options that can improve efficacy and reduce side effects compared to traditional therapies.

Phase 1

Recruiting

Led By Tim F Greten, M.D.

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

HBV infected subjects must be on antivirals and have HBV DNA < 100IU/mL

Treatment-related toxicities must be resolved to <= grade 1

Must not have

Participants requiring anticoagulation or anti-platelet therapy

Prior administration of anti-PD-1 or anti-PD-L1 antibodies within 8 weeks prior to treatment initiation

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 15 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new treatment where a person's immune cells are modified to better fight liver cancer. It targets adults with a specific type of liver cancer that has a particular marker. The modified cells are designed to find and kill cancer cells. This marker is highly expressed in a common type of liver cancer and has been targeted in various innovative therapies for liver cancer.

Who is the study for?

Adults over 18 with advanced liver cancer expressing GPC3, who have tried or can't tolerate standard chemotherapy. They must be able to undergo a tumor biopsy, have measurable disease not suitable for surgery or transplantation, and proper organ function. Pregnant women and those with severe illnesses or certain medical conditions are excluded.

What is being tested?

The trial is testing CAR-T cell therapy where patients' T cells are modified to fight liver cancer better. Participants will receive chemo drugs fludarabine and cyclophosphamide before getting their modified T cells back via IV. The study includes long-term follow-up.

What are the potential side effects?

Potential side effects include reactions from the infusion of modified T cells, effects from chemotherapy like nausea and low blood counts, increased risk of infection, fatigue, and possibly autoimmune-like symptoms due to immune system activation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have hepatitis B, am on antivirals, and my HBV DNA level is below 100IU/mL.

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My side effects from previous treatments are mild.

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I am 18 years old or older.

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I can have a biopsy to check my tumor for GPC3.

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My tumor shows high GPC3 levels in recent tests.

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I am fully active or can carry out light work.

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My liver cancer worsened after the first treatment or I couldn't tolerate the standard chemotherapy.

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My condition cannot be cured with surgery or other similar treatments.

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My heart pumps well and I don't have serious fluid around it.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am on blood thinners.

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I haven't received anti-PD-1 or anti-PD-L1 treatments in the last 8 weeks.

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My liver function is moderately to severely impaired.

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I have or had an autoimmune disease that could come back.

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I haven't taken any corticosteroids in the last 14 days.

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I have a history of seizures.

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My cancer has spread to my brain.

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I am HIV-positive.

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I do not have any uncontrolled illnesses.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 15 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~15 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 15 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

T-Lymphocyte

Secondary study objectives

To characterize overall survival (OS)

To determine the best overall response (BOR) rate according to Response Evaluation Criteria (by RECIST v 1.1) of treatment with T-cells, expressing a novel humanized anti-GPC3 chimeric antigen receptor in participants with advanced HCC, expressi...

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: 2/ Arm 2Experimental Treatment3 Interventions

MTD of CAR-T cells

Group II: 1/ Arm 1Experimental Treatment3 Interventions

Escalating doses of CAR-T cells

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cyclophosphamide

2010

Completed Phase 4

~2310

Fludarabine

2012

Completed Phase 4

~1860

0 / 18Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for liver cancer include targeted therapies, immunotherapies, and chemotherapy. Targeted therapies, such as sorafenib and lenvatinib, inhibit specific molecules involved in tumor growth and angiogenesis. Immunotherapies, like Anti-GPC3 CAR-T cells, involve modifying a patient's T cells to target and destroy cancer cells expressing specific antigens like GPC3. Chemotherapy uses cytotoxic drugs to kill rapidly dividing cancer cells. These mechanisms are crucial for liver cancer patients as they offer personalized treatment options that can improve efficacy and reduce side effects compared to traditional therapies.

Emerging pathways for precision medicine in management of cholangiocarcinoma.