What side effects are associated with this type of intervention?

Common treatments for bile duct cancer, such as the combination of Autologous Tumor Infiltrating Lymphocytes (TIL) and high-dose aldesleukin, can lead to several side effects. TIL therapy, which involves the infusion of immune cells that target cancer, may cause immune-related adverse effects such as fever, chills, fatigue, and potential autoimmune reactions. High-dose aldesleukin, used to support TIL growth and activity, can result in severe side effects including capillary leak syndrome, hypotension, renal dysfunction, and cardiac issues. Additionally, systemic cancer therapies, including chemotherapy and immunotherapy, may cause alopecia, nausea, vomiting, fatigue, and increased risk of infections due to immunosuppression.

What prior FDA approvals exist?

The FDA has approved several treatments for bile duct cancer, though none specifically mirror the combination of Autologous Tumor Infiltrating Lymphocytes (TIL) and high-dose aldesleukin. Current standard treatments include chemotherapy agents like gemcitabine and cisplatin. Immunotherapy options, such as pembrolizumab, have shown promise in other cancers but are still under investigation for bile duct cancer. Targeted therapies, including FGFR inhibitors and IDH1 inhibitors, have also been explored. The trial involving TIL and aldesleukin represents a novel approach, leveraging the body's immune system to target and attack cancer cells, supported by cytokine therapy to enhance TIL efficacy.

What other types of research exist?

Promising novel alternatives for bile duct cancer treatment include FGFR inhibitors like pemigatinib, which have shown efficacy in previously treated, locally advanced, or metastatic cholangiocarcinoma. Additionally, immune checkpoint inhibitors targeting PD-1 or PD-L1, such as pembrolizumab and avelumab, are being evaluated and may offer potential benefits. These therapies represent emerging options that could be considered in 2024.

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CAR T-cell Therapy

TIL Therapy for Biliary Tract Cancer

Phase 2

Recruiting

Led By Udai S Kammula,, MD

Research Sponsored by Udai Kammula

Eligibility Criteria Checklist

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

Must have

Patients must be co-enrolled on the companion protocol HCC 17-220 (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies) and have available TIL cultures for therapy

Patients with distant metastatic spread must be refractory to approved standard systemic therapies (such as gemcitabine, cisplatin, or equivalents) if they are eligible to receive these treatments.

Must not have

Active systemic infections (e.g.: requiring anti-infective treatment), coagulation disorders or any other active major medical illnesses

Documented FEV1 less than or equal to 60% predicted tested in patients with: A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years). Symptoms of respiratory dysfunction

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial uses a special chemotherapy followed by the patient's own lab-grown immune cells and a drug to boost the immune system. It targets patients with advanced biliary tract cancers, which are difficult to treat. The process involves removing tumor cells, growing immune cells in a lab, reducing the patient's existing immune cells, and then infusing the lab-grown cells back into the patient.

Who is the study for?

This trial is for adults aged 18-75 with advanced, recurrent, or metastatic biliary tract cancers who have not responded to standard treatments. They must be able to handle specific chemotherapy and high-dose aldesleukin, sign informed consent, have an ECOG performance status of 0 or 1 (fully active or restricted in physically strenuous activity but ambulatory), and agree to birth control measures. Those with small, stable brain metastases may qualify.

What is being tested?

The study tests the effectiveness of Tumor Infiltrating Lymphocytes (TIL) therapy combined with a non-myeloablative lymphodepleting regimen followed by high-dose aldesleukin in patients with biliary tract cancer. It's a Phase 2 trial aiming to see if this approach can shrink tumors in those who haven't had success with other treatments.

What are the potential side effects?

Potential side effects include reactions from the immune system due to TIL infusion and high-dose aldesleukin such as flu-like symptoms, fatigue, rash, possible organ inflammation and risk of infection. The preparative chemotherapy could also cause typical chemo-related side effects like nausea, hair loss and blood cell count decreases.

Eligibility Criteria

Inclusion Criteria

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

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I am enrolled in HCC 17-220 and have TIL cultures ready for therapy.

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My cancer has spread and does not respond to standard treatments like gemcitabine or cisplatin.

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I have advanced or spreading cancer in my bile ducts, gallbladder, or nearby areas.

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My cancer has spread and does not respond to standard treatments like gemcitabine or cisplatin.

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My local cancer cannot be removed with standard surgery.

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My cancer cannot be removed with standard surgery.

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I am between 18 and 75 years old.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am enrolled in HCC 17-220 and have TIL cultures ready for therapy.

Exclusion Criteria

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

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I do not have any active infections, bleeding disorders, or major illnesses.

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My lung function is reduced, I've smoked heavily, and I have breathing problems.

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I have a history of a serious autoimmune disease affecting major organs.

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I am currently taking steroid medication.

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I have had symptoms of heart disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 24 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Objective Response Rate (ORR)

Secondary study objectives

Complete response rate (CRR)

Disease control rate (DCR)

Duration of Response (DOR)

+4 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Tumor Infiltrating Lymphocytes (TIL)Experimental Treatment1 Intervention

Patients with locally advanced, recurrent, or metastatic biliary tract cancers will receive the lymphocyte depleting preparative regimen consisting of fludarabine and cyclophosphamide, followed by infusion of up to 2x10\^11 lymphocytes infused intravenously through a central vein catheter and Aldesleukin, administered at a dose of 600,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to a maximum of 6 doses.

0 / 14Eligibility 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

The most common treatments for bile duct cancer include chemotherapy, radiotherapy, targeted therapy, and immunotherapy. In the context of immunotherapy, treatments like Autologous Tumor Infiltrating Lymphocytes (TIL) and high-dose aldesleukin are particularly noteworthy. TILs are immune cells extracted from the patient's tumor, expanded in the lab, and then reintroduced into the patient to target and attack cancer cells directly. High-dose aldesleukin (a form of interleukin-2) is administered to support the growth and activity of these TILs, enhancing their ability to combat the cancer. This approach is significant for bile duct cancer patients as it leverages the body's own immune system to fight the cancer, potentially leading to more effective and personalized treatment outcomes.

Cytoreductive surgery in the management of metastatic renal cell carcinoma: the UCLA experience.[Guideline for the diagnosis and treatment of gallbladder carcinoma (2019 edition)].