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

Recruiting at 11 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

Trial Summary

What is the purpose of this trial?

This study will compare the safety and effects of HAI floxuridine and dexamethasone combined with the standard chemotherapy drugs gemcitabine and oxaliplatin (GemOx) with those of GemOx alone in people with untreated cholangiocarcinoma that cannot be removed with surgery. The researchers want to find out whether the study treatment works better than the standard chemotherapy to delay progression of disease. For the study treatment to be considered better than the standard treatment, the study treatment should increase the time until progression of disease by an average of 3 months, compared with the usual approach.

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.

What data supports the effectiveness of the drug combination used in the trial for bile duct cancer?

Research shows that the combination of gemcitabine, oxaliplatin, and 5-fluorouracil (5-FU) is active in treating bile duct cancer, with studies indicating these drugs work well together and have manageable side effects. Additionally, gemcitabine has been effective in controlling cancer relapse after surgery in bile duct cancer patients. ^{1 2 3 4 5}

Is the chemotherapy treatment with Gemcitabine, Oxaliplatin, and 5-FU safe for humans?

Research shows that Gemcitabine, Oxaliplatin, and 5-FU have been used safely in treating bile duct and gallbladder cancers, with studies focusing on their safety and effectiveness. These drugs have non-overlapping toxicity, meaning they don't usually cause the same side effects, which can make them safer to use together. ^{1 2 6 7 8}

How is the chemotherapy treatment with Gemcitabine and Oxaliplatin unique for bile duct cancer?

This treatment combines Gemcitabine and Oxaliplatin, which are drugs that work together to fight bile duct cancer with different mechanisms and have non-overlapping side effects. It is notable for being administered in an outpatient setting, requiring only three visits per month, making it more convenient for patients. ^{1 2 3 9 10}

Research Team

Andrea Cercek, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 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]

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 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 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]

References

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

Gemcitabine, oxaliplatin and 5-FU in advanced bile duct and gallbladder carcinoma: two parallel, multicentre phase-II trials. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Phase I study of biweekly oxaliplatin, gemcitabine and capecitabine in patients with advanced upper gastrointestinal malignancies. [2022]

3. United States 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. [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

[Experience of gemcitabine therapy after non-curative resection for biliary tract cancer]. [2022]

5. Switzerland 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. [2020]

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

Weekly gemcitabine for the treatment of biliary tract and gallbladder cancer. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Evidence on Palliative Gemcitabine and Oxaliplatin (GemOx) Combination Chemotherapy in Advanced Biliary Tract Cancer. [2021]

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

Efficacy and safety of gemcitabine-based chemotherapies in biliary tract cancer: a meta-analysis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Outpatient chemotherapy with gemcitabine and oxaliplatin in patients with biliary tract cancer. [2022]

10. Germany 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. [2022]