Combination Chemotherapy for Biliary Tract Cancer

Recruiting at3 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Georgetown University

Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors

Disqualifiers: Ampullary adenocarcinoma, Pregnancy, CNS metastases, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot have had anti-cancer treatment within 3 weeks before enrolling, and you must avoid strong CYP3A4 inducers, inhibitors, or strong UGT1A1 inhibitors within 2 weeks of starting the study.

What data supports the idea that Combination Chemotherapy for Biliary Tract Cancer is an effective treatment?

The available research shows that using a combination of drugs, including liposomal irinotecan, fluorouracil, and leucovorin, can be effective for treating advanced biliary tract cancer. In one study, this combination helped control the disease in about 54.5% of patients and extended their lives by an average of 12.4 months after starting the treatment. Another study, the NIFTY trial, confirmed the benefits of this combination for patients whose cancer had worsened after initial treatments. These results suggest that this combination therapy can be a promising option for patients with advanced biliary tract cancer. ^{1 2 3 4 5}

What safety data is available for the chemotherapy treatment for biliary tract cancer?

The safety data for the combination chemotherapy treatment involving liposomal irinotecan (nal-IRI), fluorouracil (5-FU), and leucovorin (LV) for biliary tract cancer shows an acceptable safety profile. The NIFTY trial and other studies have demonstrated its efficacy and tolerability as a second-line treatment. In the NIFTY trial, the combination was used for patients with advanced biliary tract cancer, showing promising results. A retrospective analysis at the University Hospital Cologne reported a disease control rate of 54.5% with 3 grade III toxicities. Overall, the treatment demonstrated promising antitumor potential with manageable safety concerns, justifying further investigation in randomized controlled trials. ^{1 2 3 4 6}

Is the drug used in the trial 'Combination Chemotherapy for Biliary Tract Cancer' a promising treatment?

Yes, the drug combination used in the trial shows promise because it aims to improve the effectiveness and tolerance of chemotherapy for biliary tract cancer, which is known for having a poor prognosis. Various studies have explored different combinations of drugs like 5-fluorouracil, cisplatin, gemcitabine, and others, showing potential in improving patient outcomes. ^{2 5 6 7 8}

Research Team

Benjamin Weinberg, MD

Principal Investigator

Georgetown University

Eligibility Criteria

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.

Inclusion Criteria

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

My liver, kidneys, and bone marrow are functioning well.

I have had only one chemotherapy for my advanced cancer.

Exclusion Criteria

I have a blockage in my intestines.

I have no other cancers except for certain skin, prostate, cervical, or superficial bladder cancers in the last 3 years.

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

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nanoliposomal irinotecan, leucovorin, and fluorouracil as second-line treatment for advanced biliary tract cancers

6 months

Every 2 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Fluorouracil (Anti-metabolites)
• Leucovorin (Other)
• Nanoliposomal Irinotecan (Topoisomerase I inhibitors)

Trial Overview 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.

Participant Groups

Group I: Single Arm Experimental Treatment 3 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.

Who Is Running the Clinical Trial?

Georgetown University

Lead Sponsor

Trials

355

Recruited

142,000+

Dr. Ivica Labuda

Georgetown University

Chief Executive Officer since 2022

PhD in Biochemistry and Molecular & Cellular Biology from Slovak Academy of Sciences, University of Graz, and Rutgers University

Dr. Richard Ascione

Georgetown University

Chief Medical Officer since 2023

MD from Georgetown University Medical School

Ipsen

Industry Sponsor

Trials

358

Recruited

74,600+

David Loew

Ipsen

Chief Executive Officer since 2020

BA in Business Administration and MBA from the University of St. Gallen, Switzerland

Sandra Silvestri

Ipsen

Chief Medical Officer since 2023

MD, PhD

Findings from Research

In a study of 11 patients with advanced biliary tract cancers, the combination of nanoliposomal irinotecan, leucovorin, and 5-fluorouracil (FOLFnal-IRI) showed a disease control rate of 54.5%, indicating promising antitumor potential as a second-line treatment after platinum-based chemotherapy.

The treatment was associated with a median progression-free survival of 5.1 months and an overall survival of 12.4 months, with only 3 instances of grade III toxicities, suggesting an acceptable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoliposomal irinotecan in combination with leucovorin and 5-fluorouracil in advanced biliary tract cancers. Allo, G., Can, AD., Wahba, R., et al.[2022]

The Fufiri regimen, consisting of irinotecan, folinic acid, and 5-fluorouracil, was found to be well-tolerated in patients with advanced biliary cancer, with 27% experiencing severe drug-related side effects, primarily diarrhea and leukopenia.

Despite its tolerability, the treatment showed only modest efficacy, with a 10% objective response rate and median overall survival of 166 days for intrahepatic cholangiocarcinoma and 273 days for gallbladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan with 5-FU/FA in advanced biliary tract adenocarcinomas: a multicenter phase II trial. Feisthammel, J., Schoppmeyer, K., Mössner, J., et al.[2018]

In a phase 2b study involving 174 patients with advanced biliary tract cancer, the combination of liposomal irinotecan, fluorouracil, and leucovorin significantly improved progression-free survival compared to fluorouracil and leucovorin alone, with a median survival of 7.1 months versus 1.4 months.

While the treatment showed efficacy, it was associated with higher rates of serious adverse events, particularly neutropenia and fatigue, but no treatment-related deaths were reported, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study. Yoo, C., Kim, KP., Jeong, JH., et al.[2022]

The NIFTY trial showed that the combination of liposomal irinotecan (nal-IRI) with fluorouracil (FU) and leucovorin (LV) significantly improved progression-free survival (PFS) in patients with advanced biliary tract cancer, with a median PFS of 4.2 months compared to 1.7 months for FU/LV alone.

This updated analysis, based on 178 patients over a follow-up period of 1.3 years, indicates that nal-IRI plus FU/LV is a promising second-line treatment option for patients whose cancer progressed after initial treatment with gemcitabine and cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment With Liposomal Irinotecan Plus Fluorouracil and Leucovorin for Patients With Previously Treated Metastatic Biliary Tract Cancer: The Phase 2b NIFTY Randomized Clinical Trial. Hyung, J., Kim, I., Kim, KP., et al.[2023]

The LV5FU2-P chemotherapy regimen demonstrated a 34% objective response rate in 29 patients with advanced or metastatic biliary tract carcinoma, indicating its potential effectiveness in treating this challenging cancer.

The treatment was well-tolerated, with no treatment-related deaths and significant improvements in patient performance status and weight, although some patients experienced grade 3 toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of leucovorin, 5-FU and cisplatin (LV5FU2-P regimen) in patients with biliary tract carcinoma. Taïeb, J., Mitry, E., Boige, V., et al.[2020]

In a study of 37 patients with advanced biliary tract cancer who did not respond to first-line gemcitabine/cisplatin treatment, the FOLFOX-4 regimen showed a median time to progression of 3.1 months, indicating moderate efficacy as a second-line treatment.

The treatment resulted in an objective response rate of 21.6% and a disease control rate of 62.2%, but also led to significant side effects, with 37.8% of patients experiencing grade 3-4 toxicities, primarily neutropenia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II FOLFOX-4 regimen as second-line treatment in advanced biliary tract cancer refractory to gemcitabine/cisplatin. He, S., Shen, J., Sun, X., et al.[2022]

In a study of 42 patients with unresectable or metastatic biliary tract or gallbladder adenocarcinoma, a combination of gemcitabine, 5-fluorouracil, and leucovorin resulted in a median survival of 9.7 months, with 57% of patients surviving 6 months or longer.

The treatment was generally manageable, with no treatment-related deaths reported, although some patients experienced severe toxicities such as nausea, fatigue, and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine, 5-fluorouracil, and leucovorin in advanced biliary tract and gallbladder carcinoma: a North Central Cancer Treatment Group phase II trial. Alberts, SR., Al-Khatib, H., Mahoney, MR., et al.[2022]

The GEMFUFOL chemotherapy regimen, which includes gemcitabine, 5-fluorouracil, and leucovorin, showed promising efficacy in treating metastatic biliary tract cancer, with a median overall survival of 8.8 months and a 1-year survival rate of 58.6% among 29 patients studied over a mean follow-up of 22.1 months.

While the treatment was generally well-tolerated, it did result in significant side effects, including neutropenia in 13.7% of patients and febrile neutropenia in 6.8%, indicating the need for careful monitoring and potential dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-week combination chemotherapy with gemcitabine, high-dose folinic acid and 5 fluorouracil (GEMFUFOL) as first-line treatment of metastatic biliary tract cancers. Unal, OU., Oztop, I., Unek, IT., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Nanoliposomal irinotecan in combination with leucovorin and 5-fluorouracil in advanced biliary tract cancers. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Irinotecan with 5-FU/FA in advanced biliary tract adenocarcinomas: a multicenter phase II trial. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Treatment With Liposomal Irinotecan Plus Fluorouracil and Leucovorin for Patients With Previously Treated Metastatic Biliary Tract Cancer: The Phase 2b NIFTY Randomized Clinical Trial. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Optimization of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of leucovorin, 5-FU and cisplatin (LV5FU2-P regimen) in patients with biliary tract carcinoma. [2020]

6. England pubmed.ncbi.nlm.nih.gov

A phase II FOLFOX-4 regimen as second-line treatment in advanced biliary tract cancer refractory to gemcitabine/cisplatin. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Gemcitabine, 5-fluorouracil, and leucovorin in advanced biliary tract and gallbladder carcinoma: a North Central Cancer Treatment Group phase II trial. [2022]

8. Thailand pubmed.ncbi.nlm.nih.gov

Two-week combination chemotherapy with gemcitabine, high-dose folinic acid and 5 fluorouracil (GEMFUFOL) as first-line treatment of metastatic biliary tract cancers. [2022]