Clinical trial NCT01862315: Hepatic Arterial Infusion (HAI) With Floxuridine (FUDR) and Dexamethasone (Dex) Combined With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma (ICC)
Official title: A Phase II Study of Hepatic Arterial Infusion (HAI) With Floxuridine (FUDR) and Dexamethasone (Dex) Combined With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma (ICC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Intrahepatic Cholangiocarcinoma
Peripheral Cholangiocarcinoma
Cholangiolar Carcinoma
Cholangiocellular Carcinoma
Keywords: Hepatic Arterial Infusion (HAI)
Floxuridine (FUDR)
Dexamethasone (DEX)
Gemcitabine
Oxaliplatin
13-066
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2013-05-24
Enrollment: 55
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 and the tumor. Liver pump treatment uses a metal pump that is surgically placed in the abdomen and gives chemotherapy directly to the liver. Systemic chemotherapy gives chemotherapy through a vein \[intravenously (IV)\] and treats the whole body. This type of treatment has been done before and had shown that people with both pump and systemic chemotherapy had improved results. The investigators hope that this combination of treatments improves the response to chemotherapy and reduces the spread of the disease.

Another purpose of this study is to learn the clinical importance of a specific type of MRI scan. The investigators would like to see if this type of MRI will help predict the response to the treatment and see if they could help the physician with their treatment plan. These scans will be done at specific time points.

The last purpose of this study is to learn more about how the tumor interacts with the chemotherapy. This will be done through a biopsy taken during surgery and blood draws at specific time points.

Permission from patients entering the study will be obtained to take normal and tumor liver biopsies at the time of surgery. These samples are voluntary and optional.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 21 years
* Histologically confirmed intrahepatic cholangiocarcinoma (also variously reported as peripheral cholangiocarcinoma, cholangiolar carcinoma or cholangiocellular carcinoma) (ICC). Confirmation of the diagnosis at MSKCC or at the enrolling institution must be obtained prior to initiation of protocol therapy.
* Clinical or radiographic evidence of metastatic disease to regional lymph nodes will be allowed, provided it is amenable to resection.
* 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 2cm in greatest diameter as per RECIST criteria.
* Disease must be considered unresectable at the time of preoperative evaluation.
* Presence of less than 70% liver involvement by cancer.
* Patients may have failed ablative therapy
* Patient previously treated with systemic chemotherapy will be eligible
* KPS ≥ 60% and be considered candidates 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
* Patients must be able to read, understand and sign informed consent
* WBC ≥ 2,000 cells/mm3
* Platelet count ≥ 75,000/mm3
* Creatinine ≤ 1.8 mg/dl
* Total bilirubin \< 1.5 mg/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 postoperative biopsies that definitively diagnose ICC, 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.
* Prior treatment with FUDR
* Prior external beam radiation 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
* Pregnant or lactating women
* History of other malignancy within the past 3 years (except non-melanoma skin cancer)
* Life expectancy less than 12 weeks
* Inability to comply with study and/or followup procedures
* History of peripheral neuropathy (Note: this does not apply to Cohort 3)

Primary outcomes:
measure: progression free survival for Cohort 1
timeFrame: 6 months
measure: progression free survival for Cohort 2
timeFrame: 3 months
measure: response for Cohort 3
timeFrame: 6 months
Secondary outcomes:
measure: Correlative objective of of dynamic contrast enhanced (DCE)-MRI imaging of intrahepatic cholangiocarcinoma before treatment and early during the course of treatment.
timeFrame: 1 year
measure: Correlative objective of of dynamic contrast enhanced DWI of intrahepatic cholangiocarcinoma before treatment and early during the course of treatment.
timeFrame: 1 year
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: William Jarnagin, MD
role: PRINCIPAL_INVESTIGATOR
References: