What side effects are associated with this type of intervention?

Common treatments for bile duct cancer, such as the combination of Durvalumab (PD-L1 inhibitor) and Tremelimumab (CTLA-4 inhibitor) with Gemcitabine and Cisplatin (platinum-based chemotherapy), can have several side effects. Immunotherapy agents like Durvalumab and Tremelimumab may cause immune-related adverse events, including fatigue, diarrhea, rash, and endocrinopathies. Platinum-based chemotherapy with Gemcitabine and Cisplatin is associated with side effects such as nausea, vomiting, myelosuppression (leading to anemia, leukopenia, and thrombocytopenia), nephrotoxicity, and peripheral neuropathy. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for bile duct cancer, including combinations of immunotherapy and chemotherapy. Notably, Gemcitabine and Cisplatin are commonly used platinum-based chemotherapies for this cancer type. While specific FDA approvals for the combination of Durvalumab (PD-L1 Inhibitor) and Tremelimumab (CTLA-4 Inhibitor) with Gemcitabine and Cisplatin are not detailed in the provided context, these agents are being actively studied in clinical trials for their potential efficacy in treating intrahepatic cholangiocarcinoma. The combination aims to improve resection rates and overall survival by leveraging the immune system alongside traditional chemotherapy.

What other types of research exist?

Promising alternatives to Durvalumab and Tremelimumab with Gemcitabine and Cisplatin for bile duct cancer include: 1) Nivolumab (PD-1 Inhibitor) and Ipilimumab (CTLA-4 Inhibitor) combination therapy, which has shown efficacy in advanced biliary tract cancers. 2) Pembrolizumab (PD-1 Inhibitor) for patients with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H). 3) Targeted therapies such as Pemigatinib for FGFR2 gene fusion-positive cholangiocarcinoma and Ivosidenib for IDH1-mutant advanced cholangiocarcinoma. These alternatives have demonstrated potential in clinical trials and may offer new treatment options for bile duct cancer patients in 2024.

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Checkpoint Inhibitor

Immunotherapy + Chemotherapy for Bile Duct Cancer (ICC Trial)

Phase 1 & 2

Waitlist Available

Led By Olumide Gbolahan, MD

Research Sponsored by University of Alabama at Birmingham

Eligibility Criteria Checklist

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

Must have

T1b-T4 tumor thought to be technically resectable

Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients

Must not have

Has had severe hypersensitivity (≥ Grade 3) to anti-PD1/PDL1 or anti-CTLA4 therapy and/or any of their excipients in the past

Patients with distant extrahepatic metastatic disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline through 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of immunotherapy and chemotherapy in patients with a specific type of liver cancer. The goal is to improve surgery outcomes and reduce cancer recurrence. Patients will receive treatment, and their response will be monitored through imaging scans.

Who is the study for?

Adults over 18 with intrahepatic cholangiocarcinoma that's considered resectable, but high-risk for recurrence. They should have a good performance status (ECOG 0 or 1), weigh more than 30 kg, and have proper organ/marrow function. Women must not be pregnant and participants must consent to biopsies. Exclusions include prior treatments for this cancer type, other active cancers or severe illnesses, known allergies to trial drugs, recent vaccines, immunosuppressant use, or unwillingness to use birth control.

What is being tested?

The trial is testing the effectiveness of combining two immunotherapy drugs (durvalumab and tremelimumab) with platinum-based chemotherapy (gemcitabine and cisplatin). The goal is to see if this treatment can improve surgery outcomes by shrinking tumors before removal and potentially extend survival while also identifying biomarkers predicting therapy response.

What are the potential side effects?

Possible side effects may include immune-related inflammation in various organs, reactions at the infusion site where medication enters the body through a vein, fatigue, digestive issues like nausea or diarrhea, blood cell count changes which could increase infection risk. Each patient might experience these differently.

Eligibility Criteria

Inclusion Criteria

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

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My tumor is considered operable by my doctor.

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I am post-menopausal or not pregnant if pre-menopausal.

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My cancer has spread to nearby lymph nodes but can be surgically removed.

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My cancer has multiple tumors or satellite lesions in the same lung lobe and can be surgically removed.

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I am fully active or can carry out light work.

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My body weight is over 30 kg.

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My cancer is high risk due to its size, spread, or involvement with blood vessels but can still be surgically removed.

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My cancer is confirmed as intrahepatic cholangiocarcinoma through tests.

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My cancer has not spread beyond my liver.

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My tumor is larger than 5cm and needs treatment to shrink it before surgery.

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My tumor, despite having blood vessel involvement, can be surgically removed.

Exclusion Criteria

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

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I've had a severe allergic reaction to specific cancer immunotherapies before.

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My cancer has spread to areas far from the liver.

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I have cancer of the ampulla, bile ducts outside the liver, or gallbladder.

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I have received treatment for a specific type of liver cancer before surgery was considered.

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I do not have active infections like TB, hepatitis B, C, or HIV.

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I do not have any unmanaged ongoing illnesses.

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I have not had major surgery in the last 28 days.

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My cancer is not adenocarcinoma or a mix with hepatocellular carcinoma.

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I have or had an autoimmune or inflammatory disorder.

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I am not pregnant, breastfeeding, and if capable of having children, I agree to use birth control.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline through 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline through 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline through 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

Secondary study objectives

Determine Changes in the Tumor mRNA Gene Expression Pattern, Phenotype of Circulating Cytotoxic T Cells, and Changes in Circulating Markers of Immunogenic Cell Death Following Treatment With Intervention Agents

Determine the Safety of the Combination of Intervention Agents by Assessing the Percentage of Patients Who Experience Dose Limiting Toxicities or Develop Adverse Reactions

The Percentage of Participants That Complete Preoperative Therapy

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: Novel combination of chemotherapy and immunotherapyExperimental Treatment1 Intervention

This study has one arm. All enrolled patients will receive a combination of a platinum based chemotherapy regimen (gemcitabine and cisplatin) and a combination of two immune check point inhibitors, anti- CTLA4 (Tremelimumab) and anti PDL-1 (durvalumab). Gemcitabine will be administered (gemzar) intravenously, 1000mg/m2 on Day 1 and Day 8 of a 21 day cycle for up to 4 cycles. Cisplatin (Platinol) will be administered intravenously, 25mg//m2 on Day 1 and Day 8 of a 21 day cycle for up to 4 cycles. Tremelimumab will be administered intravenously, 300mg flat dose, on Day 1 of cycle 1 only. Durvalumab will be administered intravenously 1500mg on Day 1 of a 21 day cycle for 4 cycles.

0 / 21Eligibility 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

Durvalumab is a PD-L1 inhibitor that works by blocking the interaction between PD-L1 on tumor cells and PD-1 on T-cells, thereby enhancing the immune system's ability to attack cancer cells. Tremelimumab is a CTLA-4 inhibitor that blocks the CTLA-4 checkpoint on T-cells, further promoting an immune response against cancer cells. Gemcitabine and Cisplatin are platinum-based chemotherapies; Gemcitabine interferes with DNA synthesis, while Cisplatin causes DNA crosslinking, both leading to cancer cell death. These treatments are significant for bile duct cancer patients as they combine immune checkpoint inhibition with traditional chemotherapy, potentially improving response rates and survival outcomes by attacking the cancer through multiple mechanisms.

Silmitasertib plus gemcitabine and cisplatin first-line therapy in locally advanced/metastatic cholangiocarcinoma: A Phase 1b/2 study.Dramatic response to dabrafenib and trametinib combination in a BRAF V600E-mutated cholangiocarcinoma: implementation of a molecular tumour board and next-generation sequencing for personalized medicine.