Gemcitabine and Oxaliplatin Chemotherapy With or Without a Floxuridine and Dexamethasone Pump in People With Cholangiocarcinoma That Cannot Be Removed With Surgery

A Randomized Phase II Study of Systemic Chemotherapy With or Without HAI FUDR/Dexamethasone in Patients With Unresectable Intrahepatic Cholangiocarcinoma

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.

Study Overview

• Status: Recruiting
• Conditions: Intrahepatic Cholangiocarcinoma
• Intervention / Treatment: Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Dexamethasone; Drug: Floxuridine (FUDR); Device: Implanted Medical Device

• Study Type: Interventional
• Enrollment (Estimated): 164
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: William Jarnagin, MD; Phone Number: 212-639-7601
• Study Contact Backup: Name: Andrea Cercek, MD; Phone Number: 646-888-4189; Email: cerceka@mskcc.org

Study Locations

• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Recruiting
    • Erasmus University (Data Collection Only)
    • Contact: Bas Groot Koerkamp, MD; Phone Number: + 31 10 704 0 704
• United States
  • Maryland
    • Bethesda, Maryland, United States, 20824
      • Active, not recruiting
      • National Heart, Lung, and Blood Institute (NIH) (Data Collection Only)
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Active, not recruiting
      • Washington University (Data Collection Only)
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Basking Ridge - Limited Protocol Activities
      • Contact: Andrea Cercek, MD; Phone Number: 646-888-4189
      • Principal Investigator: Andrea Cercek, MD
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth - Limited Protocol Activities
      • Contact: Andrea Cercek, MD; Phone Number: 646-888-4189
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen - Limited Protocol Activities
      • Contact: Andrea Cercek, MD; Phone Number: 646-888-4189
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Commack - Limited Protocol Activities
      • Principal Investigator: Andera Cercek, MD
      • Contact: Andrea Cercek, MD; Phone Number: 646-888-4189
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester - Limited Protocol Activities
      • Contact: Andrea Cercek, MD; Phone Number: 646-888-4189
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Andrew Cercek, MD; Phone Number: 646-888-4189
    • Uniondale, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau - Limited Protocol Activities
      • Contact: Andrea Cercek, MD; Phone Number: 646-888-4189
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Active, not recruiting
      • Duke University (Data Collection Only)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• ECOG 0-1
• Histologically confirmed intrahepatic cholangiocarcinoma (also variously reported as peripheral cholangiocarcinoma, cholangiolar carcinoma or cholangiocellular carcinoma) (IHC). Confirmation of the diagnosis at MSKCC or at the enrolling institution must be obtained prior to randomization.
• Clinical or radiographic evidence of metastatic disease confined to the liver. Note: presence of regional (porta hepatis) lymph node metastases will be allowed, provided they are amenable to resection. (Note: If peritoneal or other extrahepatic disease is found at time of pump placement, the pump will not be implanted. The patient will be removed from study, deemed nonevaluable and will not count toward the overall study accrual.)
• Radiographically measurable disease. Measurable disease is defined as disease that can be assessed with 2-dimensional measurements on a cross-sectional imaging. Minimum lesion size is 2 cm in greatest diameter as per RECIST criteria.
• Disease must be considered unresectable at the time of preoperative evaluation.*
• Considered candidate for general anesthesia, abdominal exploration and hepatic artery pump placement.
• Patients with chronic hepatitis and/or cirrhosis are eligible, but must be Child-Pugh class A.
• WBC ≥ 2,000/mcL , ANC ≥ 1000/mcL
• Platelet count ≥ 75,000/mcL
• Creatinine ≤ 1.8 mg/dL
• Total bilirubin < 1.5 mg/dL
• Hgb > 7 g/dL The % involvement of the liver will be determined by radiologists after review of imaging

Exclusion Criteria:

• Presence of distant metastatic disease. Patients will undergo radiographic evaluation to exclude the possibility of distant metastatic disease. For patients who have undergone pre- or post-operative biopsies that definitively diagnose IHC, the diagnostic studies may be modified at the discretion of the MSKCC Principal Investigator. Clinical or radiographic evidence of metastatic disease to regional lymph nodes will be allowed, provided it is amenable to resection.
• Patients previously treated with systemic chemotherapy for IHC will be non-eligible.
• Prior treatment with FUDR.
• Prior external beam radiation therapy to the liver.
• Prior ablative therapy to the liver.
• Diagnosis of sclerosing cholangitis.
• Clinical evidence or portal hypertension (ascites, gastroesophageal varices, or portal vein thrombosis; surgically related ascites does not exclude the patient).
• Active infection within one week prior to HAI placement.
• Pregnant or lactating women.
• History of other malignancy within the past 3 years except with early stage/localized cancer that was surgically resected or radiation treatment that would yield the same result as surgery within the past 3 years.
• Life expectancy <12 weeks.
• Inability to comply with study and/or follow-up procedures.
• History of peripheral neuropathy. There is no exclusion of patients based on sex, ethnicity or race. For these reasons, the study results are expected to be generalizable to the Medicare beneficiary population.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: GemOx alone (Arm 2); 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.	Drug: Gemcitabine; See arm for details.; Drug: Oxaliplatin; See arm for details.
Experimental: HAI FUDR plus GemOx (Arm 1); 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.	Drug: Gemcitabine; See arm for details.; Drug: Oxaliplatin; See arm for details.; Drug: Dexamethasone; See arm for details.; Drug: Floxuridine (FUDR); See arm for details.; Device: Implanted Medical Device; Implanted hepatic arterial infusion pump by surgical oncology, to deliver HAI therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
assess progression-free survival (PFS)	will be done using RECIST (version 1.1).	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Andrea Cercek, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• Blair AB, Alobuia WM, Palta M, Raman SS, Levine MH, Benson AB 3rd, D'Angelica MI, Cloyd JM. Locoregional Treatment Options for Locally Advanced Intrahepatic Cholangiocarcinoma. J Natl Compr Canc Netw. 2025 Aug 14;23(9):e257085. doi: 10.6004/jnccn.2025.7085.

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2021
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: May 7, 2021
• First Submitted That Met QC Criteria: May 17, 2021
• First Posted (Actual): May 18, 2021

Study Record Updates

• Last Update Posted (Actual): August 17, 2026
• Last Update Submitted That Met QC Criteria: August 13, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Gemcitabine; Oxaliplatin; Floxuridine; Dexamethasone Pump; 20-348
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cholangiocarcinoma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Polycyclic Compounds; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Nucleosides; Pregnadienetriols; Deoxyribonucleosides; Deoxyuridine; Uridine; Oxaliplatin; Gemcitabine; Dexamethasone; Floxuridine
• Other Study ID Numbers: 20-348

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes