An official website of the United States government
Government Funding Lapse Because of a lapse in government funding, the information on this website may not be up to date, transactions submitted via the website may not be processed, and the agency may not be able to respond to inquiries until appropriations are enacted.
The NIH Clinical Center (the research hospital of NIH) is open. For more details about its operating status, please visit cc.nih.gov.
Updates regarding government operating status and resumption of normal operations can be found at opm.gov.
Gemcitabine and Oxaliplatin Chemotherapy with or without a Floxuridine and Dexamethasone Pump in Patients with Cholangiocarcinoma that Cannot Be Removed with Surgery
Trial Status: active
This phase II trial studies the effects of gemcitabine and oxaliplatin with or without a floxuridine and dexamethasone pump in patients with cancer in the small tubes that carry bile through the liver (cholangiocarcinoma) that cannot be removed with surgery. Researchers are combining the chemotherapy drugs gemcitabine and oxaliplatin (GemOx; the standard treatment for this type of cancer) with another treatment that is delivered by a pump device called a hepatic arterial infusion (HAI) pump. The HAI pump, which is implanted in the abdomen during a surgical procedure, continuously delivers the drugs floxuridine and dexamethasone directly to the liver. Floxuridine interferes with the body’s genetic information (DNA and RNA) in ways that prevent cancer cells from growing and reproducing. Dexamethasone helps to minimize swelling and other side effects caused by floxuridine. Gemcitabine and oxaliplatin both work by interfering with cancer cell DNA. Giving gemcitabine and oxaliplatin with floxuridine and dexamethasone pump may work better in treating patients with cholangiocarcinoma that cannot be removed by surgery.
Inclusion Criteria
Age >=18 years
Eastern Cooperative Oncology Group (ECOG) 0-1
Histologically confirmed intrahepatic cholangiocarcinoma (also variously reported as peripheral cholangiocarcinoma, cholangiolar carcinoma or cholangiocellular carcinoma) (IHC). Confirmation of the diagnosis at Memorial Sloan Kettering Cancer Center (MSKCC) or at the enrolling institution must be obtained prior to initiation of protocol therapy
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 Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Disease must be considered unresectable at the time of preoperative evaluation
* Unresectability will be determined by experienced hepato-pancreatico-biliary (HPB) surgeons after review of cross -sectional imaging studies. Unresectability may be due to multifocal liver disease, the presence of metastatic disease to regional lymph nodes or locally advanced disease with extensive involvement of major inflow hepatic pedicles and/or hepatic venous drainage. The percent involvement of the liver will be determined by radiologists after review of imaging
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
White blood count (WBC) >= 2,000/mcL
Absolute neutrophil count (ANC) >= 1000/mcL
Platelet count >= 75,000/mcL
Creatinine =< 1.8 mg/dL
Total bilirubin < 1.5 mg/dL
Hemoglobin (hgb) > 7 g/dL
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
Additional locations may be listed on ClinicalTrials.gov for NCT04891289.
I. Compare the progression-free survival (PFS) of hepatic arterial infusion (HAI) floxuridine/dexamethasone (FUDR/Dex) in combination with systemic gemcitabine/oxaliplatin (GemOx) versus systemic GemOx only.
SECONDARY OBJECTIVES:
I. Compare the overall survival in first-line HAI FUDR/Dex in combination with GemOx versus systemic GemOx only.
II. Estimate the overall response rate (complete response [CR] + partial response [PR]) between treatment groups.
III. Estimate the time to first recurrence patterns between treatment groups.
IV. Describe the toxicity rates separately for each treatment groups.
V. Define the mutational pattern of intrahepatic cholangiocarcinoma (IHC) and determine the extent to which genomic features and intratumoral heterogeneity correlate with treatment response and survival.
VI. Assess circulating cell-free deoxyribonucleic acid (cfDNA) and correlate with treatment response and survival outcomes.
VII. Assess tumor heterogeneity and correlation with treatment response using quantitative imaging techniques (radiomics).
VIII. Assess the correlation between texture features and intratumoral heterogeneity.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive floxuridine and dexamethasone via HAI pump continuously on days 1-14 of each cycle, and gemcitabine intravenously (IV) over 30 minutes and oxaliplatin IV over 120 minutes on day 15 of cycle 1 and days 1 and 15 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients gemcitabine IV over 30 minutes and oxaliplatin IV over 120 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If a patient in Arm 2 has confirmed intrahepatic progression of disease they will be able to cross over to Arm 1.
After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 3 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center