HAI Chemotherapy for Bile Duct Cancer

No longer recruiting at 6 trial locations

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: 4

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of liver pump chemotherapy (Hepatic Arterial Infusion, or HAI) and IV chemotherapy to evaluate their effectiveness against bile duct cancer. Researchers aim to enhance treatment efficacy and slow cancer spread with this combination. They are also studying a special MRI scan to determine if it can assist doctors in planning better treatments. Individuals with bile duct cancer that cannot be surgically removed and who have previously undergone chemotherapy may be suitable candidates for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 trial coordinators or your doctor.

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

A previous study found that delivering floxuridine directly to the liver was generally well-tolerated, though some patients experienced significant side effects. The most common serious side effects involved changes in liver function test results. Most patients did not have high levels of floxuridine in their bloodstream, indicating that the drug primarily stays in the liver.

Research has shown that gemcitabine is generally safe for people with bile duct cancer. While serious side effects can occur, they are uncommon.

Oxaliplatin may cause specific side effects, such as numbness or tingling in the hands and feet, which doctors monitor closely.

Since this trial is in an early phase, it primarily focuses on determining the safety of these treatments when used together. Prospective participants should know that their safety is a top priority. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for bile duct cancer, which typically involve systemic chemotherapy, the new approach being tested combines Hepatic Arterial Infusion (HAI) with chemotherapy drugs like Floxuridine (FUDR), Gemcitabine, and Oxaliplatin. Researchers are excited about this treatment because HAI delivers chemotherapy directly to the liver, potentially improving drug concentration at the tumor site while reducing systemic side effects. This targeted delivery method could lead to better outcomes and fewer side effects compared to standard chemotherapy, which works throughout the entire body. Additionally, for patients with prior oxaliplatin exposure and neuropathy, the regimen allows for the use of Gemcitabine alone, offering a tailored treatment that considers their specific needs.

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

Research has shown that hepatic arterial infusion (HAI) with the drug floxuridine may be promising for treating bile duct cancer. In this trial, participants will receive different treatment combinations. Some will receive HAI floxuridine with gemcitabine and oxaliplatin, which studies have shown can increase disease control rates to as high as 61.7%. Others will receive HAI floxuridine with gemcitabine alone, where response rates range from 7% to 27% with gemcitabine alone, but overall survival rates remain generally low. This combination aims to enhance chemotherapy effectiveness by directly targeting the liver, potentially leading to better outcomes. ^{6 7 8 9 10}

Who Is on the Research Team?

William Jarnagin, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 21 with a specific liver cancer (intrahepatic cholangiocarcinoma) that can't be removed by surgery. They should have less than 70% liver involvement, good physical function, and acceptable blood counts. People with chronic hepatitis or cirrhosis can join if it's mild. Prior chemotherapy and certain local treatments are okay, but no prior FUDR treatment or radiation to the liver.

Inclusion Criteria

Patients must be able to read, understand, and sign informed consent

Radiographically measurable disease with minimum lesion size of 2cm in greatest diameter as per RECIST criteria

Platelet count ≥ 75,000/mm3

Exclusion Criteria

Pregnant or lactating women

Life expectancy less than 12 weeks

Inability to comply with study and/or follow-up procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Placement

Surgical placement of the hepatic arterial infusion pump

2 weeks

1 visit (in-person)

Treatment

Participants receive HAI FUDR/Dex and systemic chemotherapy with Gemcitabine and Oxaliplatin

6 months

Bi-weekly visits for chemotherapy administration

Imaging and Monitoring

MRI and CT scans to monitor treatment response and tumor interaction

9 months

MRI at baseline, 3, 6, and 9 months; CT scans as part of routine care

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• Floxuridine (FUDR)
• Gemcitabine
• Hepatic Arterial Infusion (HAI)
• Oxaliplatin

Trial Overview The study tests combining liver pump treatment delivering chemotherapy directly to the liver with systemic chemotherapy treating the whole body via IV. It aims to improve response rates and control disease spread. The trial also evaluates a special MRI scan's ability to predict treatment response and guide physicians.

How Is the Trial Designed?

Group I: pts who have had prior oxaliplatin & have existing neuropathy Experimental Treatment 4 Interventions

All patients receive will receive gemcitabine alone with HAI FUDR/Dex Gemcitabine (800 mg/m2 IV over 30 minutes) alone on Days 1 and 15 of each cycle, however initiation with systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first doses of systemic chemotherapy will be given on Cycle 1, Day 15, and then every 2 weeks thereafter.

Group II: patients who have failed systemic therapy Experimental Treatment 6 Interventions

All patients receive HAI FUDR (\[0.12 mg/kg/day kg 30\] / pump flow rate)\& dexamethasone ({1 mg/m2/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. All patients receive Gemcitabine (800 mg/m2 IV over 30 minutes) \& Oxaliplatin (85 mg/m2 IV over 120 minutes) on Days 1 \& 15 of each cycle, however initiation with systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first doses of systemic chemotherapy will be given on Cycle 1, Day 15, \& then every 2 weeks thereafter. Clinical MRI examinations of the abdomen \& pelvis are obtained at baseline following surgery, prior to treatment initiation \& 4 weeks after initiation of HAI FUDR. Subsequently, the patient will undergo MRI approximately at months 3, 6 \& 9 thereafter A non-contrast CT of chest, abdomen \& pelvis will also be obtained as part of routine clinical care.

Group III: No prior chemo or responded/stable with prior chemo Experimental Treatment 6 Interventions

All patients receive HAI FUDR (\[0.12 mg/kg/day kg 30\] / pump flow rate)\& dexamethasone ({1 mg/m2/day30} 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. All patients receive Gemcitabine (800 mg/m2 IV over 30 minutes) \& Oxaliplatin (85 mg/m2 IV over 120 minutes) on Days 1 \& 15 of each cycle, however initiation with systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first doses of systemic chemotherapy will be given on Cycle 1, Day 15, \& then every 2 weeks thereafter. Clinical MRI examinations of the abdomen \& pelvis are obtained at baseline following surgery, prior to treatment initiation \& 4 weeks after initiation of HAI FUDR. Subsequently, the patient will undergo MRI approximately at months 3, 6 \& 9 thereafter A non-contrast CT of chest, abdomen \& pelvis will also be obtained as part of routine clinical care.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6494548/

Gemcitabine‐based chemotherapy for advanced biliary tract ... Overall, objective response with gemcitabine alone ranges from 7% to 27%, but median survival is only rarely longer than eight months (Park 2005; Suzuki 2010).

2. sciencedirect.com sciencedirect.com/science/article/pii/S0959804922000259

Individual patient data meta-analysis of adjuvant ... The prognosis of BTC remains dismal, as 60–70% patients are diagnosed with inoperable disease, and even after curative-intent surgical resection, the 5-year ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa0908721

Cisplatin plus Gemcitabine versus Gemcitabine for Biliary ... The 6-month progression-free survival rate was 59.3% in the cisplatin–gemcitabine group and 42.5% in the gemcitabine-only group. Figure 2.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4509359/

Gemcitabine Plus Cisplatin for Advanced Biliary Tract Cancer Median overall survival ranged from 4.6 to 11.7 months, and response rate ranged from 17.1% to 36.6%. Toxicities were generally acceptable and manageable.

5. ascopubs.org ascopubs.org/doi/10.1200/GO.24.00216

Gemcitabine Cisplatin and Durvalumab Experience in ... The median progression-free and overall survival were 8.2 and 12 months, respectively, in the overall cohort and 23.1 months in patients with ...

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

Assessment of Hepatic Arterial Infusion of Floxuridine in ... The most common grade 3 toxic effects included elevated levels noted in liver function test results, including alanine aminotransferase (7 [70 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6824231/

Assessment of Hepatic Arterial Infusion of Floxuridine in ... Unresectable intrahepatic cholangiocarcinoma (IHC) carries a poor prognosis, with a median overall survival (OS) of 11 months. Hepatic arterial ...

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 The median overall survival was 68 months with HAI therapy and 50 months for those that did not receive HAI (P = 0.0001). Studies are currently ongoing in MSKCC ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0753332223004134

Systemic exposure of floxuridine after hepatic arterial ... Overall, negligible systemic concentrations of floxuridine were detected. However, remarkably increased levels were detected in one patient.

10. ascopubs.org ascopubs.org/doi/pdf/10.1200/JCO-25-00923

Hepatic Arterial Infusion Pump Chemotherapy in Patients ... The aim of this study was to assess the effectiveness of HAIP che- motherapy with floxuridine and concurrent systemic gem-cis in patients with.