What side effects are associated with this type of intervention?

Common treatments for cholangiocarcinoma, particularly those involving Fluorouracil, Leucovorin, and Nanoliposomal Irinotecan, are associated with several side effects. Fluorouracil can cause myelosuppression, mucositis, diarrhea, and hand-foot syndrome. Leucovorin, used to enhance 5-FU's efficacy, generally has minimal side effects. Nanoliposomal Irinotecan can lead to diarrhea, neutropenia, fatigue, nausea, and vomiting. When these drugs are combined, patients may experience compounded toxicities, including severe gastrointestinal and hematologic side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for cholangiocarcinoma, focusing on various mechanisms of action. One notable approval is for the combination of fluorouracil (5-FU) and leucovorin, which inhibits DNA synthesis. Additionally, irinotecan, a topoisomerase I inhibitor, has been studied in various regimens for its efficacy in treating cholangiocarcinoma. The combination of nanoliposomal irinotecan with fluorouracil and leucovorin is currently being evaluated for its potential benefits in this cancer type, leveraging both DNA synthesis inhibition and topoisomerase I inhibition to target cancer cells.

What other types of research exist?

Promising novel alternatives for cholangiocarcinoma treatment include: 1) Durvalumab combined with gemcitabine and cisplatin, which has shown efficacy in advanced biliary tract cancer. 2) Dabrafenib plus trametinib for patients with BRAFV600E-mutated biliary tract cancer. 3) Larotrectinib for TRK fusion-positive cancers. 4) Pertuzumab and trastuzumab for HER2-positive metastatic biliary tract cancer. These therapies target specific genetic mutations or utilize immunotherapy, offering personalized treatment options.

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Combination Chemotherapy for Biliary Tract Cancer

Phase 2

Recruiting

Research Sponsored by Georgetown University

Eligibility Criteria Checklist

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

Must have

Pathologically-confirmed biliary tract cancer (cholangiocarcinoma or gallbladder adenocarcinoma), unresectable or metastatic

No more than 1 prior line of chemotherapy for unresectable or metastatic disease (adjuvant therapy does not count)

Must not have

Bowel obstruction

Ampullary adenocarcinoma

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new combination of three drugs for patients with advanced biliary tract cancers who did not respond well to their first treatment. The drugs work together to damage the cancer cells' DNA and stop them from growing. The goal is to find a better second-line treatment for these patients. Previous tests with similar drugs did not show improvement.

Who is the study for?

This trial is for adults with advanced biliary tract cancers who've had disease progression after gemcitabine and platinum chemotherapy. They should have only received one prior chemotherapy line, be in good physical condition (ECOG 0-1), and not have central nervous system metastases or severe infections recently. Pregnant women, those with certain allergies or liver diseases, and patients on strong drug inhibitors are excluded.

What is being tested?

The NAPOLI-2 study tests a combination of fluorouracil, leucovorin, and nanoliposomal irinotecan as a second-line treatment for biliary cancer following initial chemo. It aims to assess the effectiveness of this regimen in patients whose cancer has progressed despite previous treatments.

What are the potential side effects?

Potential side effects include reactions related to the digestive system like diarrhea and nausea, lowered blood cell counts leading to increased infection risk or bleeding problems, fatigue, hair loss due to irinotecan; hand-foot syndrome from fluorouracil; allergic reactions are also possible.

Eligibility Criteria

Inclusion Criteria

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

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My cancer is in the bile ducts or gallbladder and cannot be surgically removed.

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I have had only one chemotherapy for my advanced cancer.

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My cancer got worse or I couldn't tolerate treatments with gemcitabine and platinum.

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I am HIV-positive, on stable HIV treatment, without needing daily infection-preventing medicine, and my HIV is well-controlled.

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I am fully active or can carry out light work.

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I am 18 years old or older.

Exclusion Criteria

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

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I have a blockage in my intestines.

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I have been diagnosed with cancer of the ampulla of Vater.

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I haven't taken strong medication affecting liver enzymes in the last 2 weeks.

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I am not pregnant or breastfeeding.

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I have previously been treated with irinotecan or its nanoliposomal form.

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I have not had major surgery in the last 4 weeks.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 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

The efficacy of fluorouracil, leucovorin, and nanoliposomal irinotecan in advanced biliary tract cancers following progression on or intolerance of gemcitabine and platinum chemotherapy.

Secondary study objectives

Disease control rate (DCR).

Maximum change in tumor marker, CA19-9.

Median duration of disease control (DDC).

+4 more

Other study objectives

Archived tumor tissue using next-generation sequencing (NGS) and immunohistochemistry (IHC) in order to elucidate potential mutational biomarkers predictive of response to fluorouracil, leucovorin, and nanoliposomal irinotecan.

Blood for the analysis of circulating tumor DNA as a surrogate marker of disease burden.

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: Single ArmExperimental Treatment3 Interventions

Nanoliposomal irinotecan 70 mg/ IV over 90 minutes, every 14 days. Leucovorin 400 mg/ IV over 30 minutes, every 14 days. Fluorouracil 2,400 mg/m IV over 46 hours.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nanoliposomal Irinotecan

2019

Completed Phase 1

~50

Fluorouracil

2014

Completed Phase 3

~11700

Leucovorin

2005

Completed Phase 4

~6010

0 / 12Eligibility 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 cholangiocarcinoma, such as Fluorouracil (5-FU), Leucovorin, and Nanoliposomal Irinotecan, work by disrupting DNA synthesis and inhibiting topoisomerase I. Fluorouracil mimics uracil, incorporating into RNA and disrupting its function, while Leucovorin enhances 5-FU's efficacy by stabilizing its binding to thymidylate synthase. Nanoliposomal Irinotecan inhibits topoisomerase I, causing DNA damage and cell death. These mechanisms are crucial for cholangiocarcinoma patients as they specifically target the rapid cell division characteristic of cancer, potentially leading to better treatment outcomes.

Role of bile salt in regulating Mcl-1 phosphorylation and chemoresistance in hepatocellular carcinoma cells.Upregulation of topoisomerase IIalpha expression in advanced gallbladder carcinoma: a potential chemotherapeutic target.