Chemotherapy +/− FUDR/Dexamethasone Pump for Bile Duct Cancer

Recruiting at 12 trial locations

Overseen By Andrea Cercek, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: FUDR

Disqualifiers: Distant metastasis, Sclerosing cholangitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 28-day cycles, ongoing

164 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for bile duct cancer that cannot be surgically removed. Researchers aim to determine if adding HAI floxuridine (a type of chemotherapy) and dexamethasone (a corticosteroid) to standard chemotherapy (GemOx) is safer and more effective at slowing disease progression than GemOx alone. Participants diagnosed with bile duct cancer that has spread only to the liver and who have not yet received chemotherapy may be suitable for this study. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatment using hepatic arterial infusion (HAI) with floxuridine, dexamethasone, and GemOx is generally well-tolerated. Studies have found that floxuridine, when used in this manner, is safe for individuals with liver-related cancers. It exits the body quickly, which can help reduce side effects.

Some research has found that this treatment can cause mild to moderate side effects, but serious issues are rare. Most people experience symptoms like mild nausea or tiredness, common with chemotherapy, and these can usually be managed with medication.

Dexamethasone, a type of steroid, is added to help reduce inflammation and other side effects. This combination has been used safely in other trials for similar conditions.

Overall, while all treatments can have side effects, available evidence suggests this combination is relatively safe for individuals. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a potentially more targeted approach for bile duct cancer. The GemOx regimen, combining gemcitabine and oxaliplatin, is enhanced in one arm by the addition of an HAI pump delivering FUDR and dexamethasone directly to the liver, which could improve drug delivery to tumor sites. This method contrasts with conventional chemotherapy, which circulates throughout the body, potentially leading to more intense side effects. The localized delivery is hoped to maximize effectiveness while minimizing systemic side effects, which is a significant advancement over traditional treatment methods.

What evidence suggests that this trial's treatments could be effective for bile duct cancer?

Research has shown that delivering chemotherapy directly to the liver with a special pump can help treat liver-related cancers. In this trial, one treatment arm uses this method with a combination of two drugs, floxuridine (FUDR) and dexamethasone, which proved effective in 47.1% of cases where surgery isn't possible. By targeting the liver directly, this treatment can enhance effectiveness and reduce side effects. This approach is combined with another standard chemotherapy treatment called GemOx, which includes gemcitabine and oxaliplatin, in one arm of the trial. Another arm involves using GemOx alone. Studies have found that patients who received the combined treatment lived longer, potentially slowing the progression of bile duct cancer more effectively than GemOx alone. ^{5 6 7 8 9}

Who Is on the Research Team?

Andrea Cercek, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with a specific type of liver cancer called intrahepatic cholangiocarcinoma that can't be removed by surgery. Participants should have measurable disease, no prior treatments with FUDR or radiation to the liver, and must not have other cancers within the last 3 years. They need to be in good physical condition (ECOG 0-1) and able to undergo general anesthesia.

Inclusion Criteria

Platelet count ≥ 75,000/mcL

WBC ≥ 2,000/mcL , ANC ≥ 1000/mcL

Creatinine ≤ 1.8 mg/dL

Exclusion Criteria

I have had cancer before, but it was early stage and treated with surgery or radiation within the last 3 years.

I have not had an infection in the week before my planned procedure.

Pregnant or lactating women.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical HAI Pump Placement

Surgical placement of HAI pump for patients in Arm 1

2 weeks

1 visit (in-person)

Treatment

Chemotherapy with GemOx alone or with HAI FUDR/Dex for patients with unresectable cholangiocarcinoma

28-day cycles, ongoing

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• Floxuridine
• Gemcitabine
• Implanted Medical Device
• Oxaliplatin

Trial Overview The study compares standard chemotherapy (Gemcitabine and Oxaliplatin) alone versus combined with an implanted pump delivering Floxuridine and Dexamethasone directly into the liver. The goal is to see if adding the pump improves time without disease progression by at least three months compared to chemotherapy alone.

How Is the Trial Designed?

Group I: HAI FUDR plus GemOx (Arm 1) Experimental Treatment 5 Interventions

Surgical HAI pump placement. 2. HAI FUDR \[(0.12 mg/kg/day) x wt (kg) x (30ml) / pump flow rate \] and dexamethasone \[1 mg/day \* 30\] / pump flow rate \] on Day 1 of each cycle. Chemotherapy with HAI FUDR/Dex will commence no sooner than 14 days postsurgical placement of HAI pump. 3. Gemcitabine (800 mg/m2 IV over 30 minutes) and oxaliplatin (85 mg/ m2 IV over 120 minutes on Days 1 and 15 of each cycle; however, for patients in Arm 1, initiation of systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first dose of systemic chemotherapy will be given on Cycle 1, Day 15, and then every 2 weeks thereafter.

Group II: GemOx alone (Arm 2) Active Control 2 Interventions

Gemcitabine (800 mg/m2 IV over 30 minutes) and oxaliplatin (85 mg/m2 IV over approximately 120 minutes) on Days 1 and 15 of each 28-day cycle.For patients in Arm 2, systemic therapy will be administered on Days 1 and Day 15 of each Cycle on a 28-day cycle basis, compromised of Gemcitabine and Oxaliplatin. If a patient randomized to Arm 2 has intrahepatic progression on any follow-up scan during study treatment, that patient will be eligible to crossover to Arm 1 and commence to pump placement surgery and HAI FUDR treatment. Patients with any extrahepatic progression will not be eligible to utilize the crossover arm. Arm 2 patients will have 28 days from date of the scan showing intrahepatic progression to proceed to the crossover arm.

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

In a study involving 30 patients with advanced upper gastrointestinal cancers, a combination regimen of oxaliplatin, gemcitabine, and capecitabine was found to be tolerable, with a maximum tolerated dose established for the treatment.

The treatment resulted in one complete response and two partial responses, indicating potential efficacy that supports further investigation in biliary and pancreatic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of biweekly oxaliplatin, gemcitabine and capecitabine in patients with advanced upper gastrointestinal malignancies. Tan, BR., Brenner, WS., Picus, J., et al.[2022]

In a study of 30 chemotherapy-naïve patients with advanced biliary tract and gallbladder cancer, weekly gemcitabine treatment showed a 30% overall response rate, with a median time to disease progression of 7 months.

The treatment was well-tolerated, with mostly mild toxicities and no treatment-related deaths, making it a safe option, especially for patients with gallbladder cancer who had better outcomes compared to those with biliary duct cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly gemcitabine for the treatment of biliary tract and gallbladder cancer. Tsavaris, N., Kosmas, C., Gouveris, P., et al.[2022]

In a phase II trial involving 30 patients with unresectable/metastatic biliary tract cancer who had previously failed gemcitabine treatment, the combination chemotherapy of 5-fluorouracil and oxaliplatin (mFOLFOX3) showed a modest overall response rate of 7.1%, with one complete response and one partial response observed.

The treatment was associated with manageable toxicity, including some grade 3-4 hematologic issues like neutropenia (6.7%) and non-hematologic issues such as neuropathy (22.2%), but it also resulted in one treatment-related death due to neutropenic infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of mFOLFOX3 (5-fluorouracil, leucovorin, oxaliplatin) as second-line treatment after gemcitabine failure in patients with unresectable/metastatic biliary tract cancer. Hwang, IG., Jang, JS., Oh, SY., et al.[2022]

A 75-year-old man with bile duct cancer showed effective control of cancer relapse after undergoing gemcitabine therapy, starting two months post-surgery, with no severe side effects reported.

The patient has remained cancer-free for 26 months after surgery, suggesting that gemcitabine is a promising adjuvant chemotherapy option for bile duct cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Experience of gemcitabine therapy after non-curative resection for biliary tract cancer]. Fujisaki, S., Takayama, T., Takashina, M., et al.[2022]

In a study involving 72 patients with advanced bile duct cancer (BDC) and gallbladder cancer (GBC), the combination of gemcitabine, oxaliplatin, and 5-fluorouracil (5-FU) resulted in response rates of 19% for BDC and 23% for GBC, indicating some effectiveness in treating these cancers.

The median survival for patients was approximately 10 months for both BDC and GBC, but the treatment was associated with significant toxicity, including major adverse events like neutropenia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine, oxaliplatin and 5-FU in advanced bile duct and gallbladder carcinoma: two parallel, multicentre phase-II trials. Wagner, AD., Buechner-Steudel, P., Moehler, M., et al.[2022]

In a study of 28 patients with advanced biliary tract cancers, the combination of gemcitabine, 5-fluorouracil, and cisplatin resulted in an objective response rate of 32.1% and a disease control rate of 82.1%, indicating that this treatment can be effective for these difficult-to-treat cancers.

While the treatment showed promising efficacy, it also led to significant side effects, including severe neutropenia in 24.3% and thrombocytopenia in 26.5% of treatment cycles, though there were no treatment-related deaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of combination chemotherapy with gemcitabine, 5-fluorouracil and cisplatin for advanced cancers of the bile duct, gallbladder, and ampulla of Vater. Sohn, BS., Yuh, YJ., Kim, KH., et al.[2022]

In a retrospective study of 121 patients with advanced biliary tract cancer, the combination of gemcitabine and oxaliplatin (GemOx) showed a median overall survival of 8.9 months and progression-free survival of 5.3 months, indicating its effectiveness in a real-world setting.

The study found that using a lower dose of oxaliplatin (80-85 mg/m2) was well-tolerated, with only 8% of patients experiencing severe neutropenia, suggesting that dose adjustments can maintain efficacy while improving safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Evidence on Palliative Gemcitabine and Oxaliplatin (GemOx) Combination Chemotherapy in Advanced Biliary Tract Cancer. Lagenfelt, H., Blomstrand, H., Elander, NO.[2021]

Gemcitabine (Gem)-based combination chemotherapy significantly improves disease response rates and overall survival in patients with advanced biliary tract cancer, based on a meta-analysis of seven randomized trials involving 858 patients.

While Gem-based therapies show better efficacy, they are associated with a higher risk of severe hematological toxicities, such as leukopenia and anemia, indicating a need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of gemcitabine-based chemotherapies in biliary tract cancer: a meta-analysis. Liu, H., Zhang, QD., Li, ZH., et al.[2022]

The GEMOX-3 chemotherapy protocol, combining gemcitabine and oxaliplatin, showed a 71% disease control rate in 31 patients with unresectable biliary tract cancer, with a median overall survival of 11 months.

The treatment was well tolerated, with manageable side effects, allowing for outpatient administration with only three visits per month.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outpatient chemotherapy with gemcitabine and oxaliplatin in patients with biliary tract cancer. Harder, J., Riecken, B., Kummer, O., et al.[2022]

In a randomized phase II trial involving 100 patients with advanced biliary tract cancer, the combination of cisplatin and gemcitabine demonstrated a median overall survival (mOS) of 12.0 months, confirming its effectiveness as a first-line treatment.

The cisplatin and gemcitabine regimen also showed a superior tumor control rate of 79% compared to 60% for the oxaliplatin, gemcitabine, and capecitabine combination, suggesting it is the preferred treatment option for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Patients with Advanced Biliary Tract Cancer with Either Oxaliplatin, Gemcitabine, and Capecitabine or Cisplatin and Gemcitabine-A Randomized Phase II Trial. Markussen, A., Jensen, LH., Diness, LV., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9356931/

Hepatic Arterial Infusion Pump Chemotherapy for ... This systematic review describes the survival outcomes of hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine for patients with unresectable ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9724731/

Phase I trial of adjuvant hepatic arterial infusion (HAI) with ... Results: The initial dose of HAI FUDR was fixed at 0.12 mg/kg × pump volume divided by pump flow rate plus Dex infused over the first 2 weeks of a 5-week cycle.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01862315

Study Details | NCT01862315 | Hepatic Arterial Infusion ... The purpose of this study is to use both, liver pump treatment and systemic chemotherapy, to assess the effects this type of treatment has on the patient ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)40439-0/fulltext

Regional chemotherapy for unresectable primary liver cancer In summary, this study shows that continuous HAI of FUDR/dex can be an effective and safe therapy for unresectable PLC. This study also suggests an important ...

5. oaepublish.com oaepublish.com/articles/2394-5079.2024.06

Hepatic arterial infusion chemotherapy: a review with ... showed promising results for unresectable liver cancer treatment using HAI with floxuridine and dexamethasone, achieving a 47.1% response ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8228250/

Hepatic Arterial Infusion Chemotherapy for Unresectable ... The HELIX ICC (NCT04251715) is a phase II trial designed to study the efficacy and safety of systemic induction of mFOLFIRINOX, followed by HAI ...

7. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2753558

Assessment of Hepatic Arterial Infusion of Floxuridine in ... This phase 2 clinical trial evaluates the use of hepatic arterial infusion of floxuridine plus systemic administration of gemcitabine and ...

8. aacrjournals.org aacrjournals.org/mct/article/8/5/1015/93410/The-role-of-floxuridine-in-metastatic-liver

The role of floxuridine in metastatic liver disease Floxuridine (FUDR) is an ideal drug for hepatic arterial infusion (HAI) due to its short half life, steep dose response curve, high total body clearance, and ...

9. withpower.com withpower.com/trial/phase-3-cholangiocarcinoma-4-2021-3e968

FUDR/Dexamethasone Pump for Bile Duct Cancer This study will compare the safety and effects of HAI floxuridine and dexamethasone combined with the standard chemotherapy drugs gemcitabine and ...