Combination Chemotherapy for Biliary Tract Cancer

Recruiting in Palo Alto (17 mi)

+3 other 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.

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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.

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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.

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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

Participant Groups

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.

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Lombardi Comprehensive Cancer Center, Georgetown University Washington, United States

Washington University School of Medicine- Siteman Cancer Center Saint Louis, MO

Indiana University Health Melvin and Bren Simon Cancer Center Indianapolis, IN

Icahn School of Medicine at Mount Sinai New York, NY

Who Is Running the Clinical Trial?

Georgetown University Lead Sponsor

Ipsen Industry Sponsor

References

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

Nanoliposomal irinotecan in combination with leucovorin and 5-fluorouracil in advanced biliary tract cancers. [2022] Biliary tract cancers (BTC) are rare but aggressive. Due to limited anti-tumor effects of current second- and later-line treatment regimens, novel treatment options are required. Nanoliposomal irinotecan in combination with leucovorin and 5-fluorouracil (FOLFnal-IRI) achieved promising results as a second-line treatment in patients with pancreatic cancer, warranting further investigation in BTC. In the present study, a retrospective analysis of patients receiving FOLFnal-IRI after initial platinum-based chemotherapy for advanced BTC between January 2016 and August 2020 at the University Hospital Cologne (Cologne, Germany) was performed. A total of 11 patients were identified who met the inclusion criteria. A total of 4 patients (36.4%) were female and the median age was 54 years. The proportion of patients suffering from gallbladder carcinoma, intrahepatic and extrahepatic cholangiocarcinoma was 18.2, 63.6 and 9.1%, respectively. Furthermore, 7 patients (63.6%) received FOLFnal-IRI as their second-, 3 (27.3%) as third- and one (9.1%) as their fourth-line therapy. The disease control rate was 54.5% and 3 grade III toxicities were recorded. Progression-free survival and overall survival (OS) after initiation of FOLFnal-IRI was 5.1 and 12.4 months, respectively. OS after initial diagnosis was 24.7 months. FOLFnal-IRI demonstrated promising antitumor potential with an acceptable safety profile as a subsequent therapy regimen in advanced biliary tract malignancies. Further randomized controlled trials of its value as a treatment option for BTC appear justified.

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

Irinotecan with 5-FU/FA in advanced biliary tract adenocarcinomas: a multicenter phase II trial. [2018] Biliary cancer has a poor prognosis and lacks a standard palliative chemotherapy. The purpose of this prospective single-arm phase II study was to determine the activity and tolerability of irinotecan, 5-fluorouracil, and folinic acid in advanced biliary cancer.

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] The prognosis of patients with advanced biliary tract cancer who have progressed on gemcitabine plus cisplatin is dismal. We aimed to investigate the efficacy and safety of second-line liposomal irinotecan plus fluorouracil and leucovorin in patients with metastatic biliary tract cancer that has progressed on gemcitabine plus cisplatin.

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] The NIFTY trial demonstrated the benefit of treatment with second-line liposomal irinotecan (nal-IRI) plus fluorouracil (FU) and leucovorin (LV) for patients with advanced biliary tract cancer (BTC).

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] Unresectable biliary tract carcinoma (BTC) is associated with a very poor prognosis. To improve efficacy and tolerance of the 5-fluorouracil (5-FU)/cisplatin combination in BTC, we designed a new therapeutic schedule, the LV5FU2-P regimen.

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] We aimed to evaluate the efficacy and safety of oxaliplatin, 5-fluorouracil (5-FU), and leucovorin (LV) (FOLFOX-4) as second-line treatment in patients with advanced biliary tract cancer (BTC) failing gemcitabine/cisplatin first-line chemotherapy.

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] Gemcitabine has broad activity in a variety of solid tumors including biliary tract carcinomas. The authors evaluated 6-month survival, response, and toxicity associated with a combination of gemcitabine, 5-fluorouracil (5-FU), and leucovorin (LV) in patients with unresectable or metastatic biliary tract or gallbladder adenocarcinoma (ACA).

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] The aim of this study was to evaluate the efficacy and tolerability of a gemcitabine, 5-fluorouracil and leucovorin (GEMFUFOL) chemotherapy regimen as first line treatment of metastatic biliary tract cancer.