Hepatic Arterial Infusion (HAI) With Floxuridine (FUDR) and Dexamethasone (Dex) Combined With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma (ICC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01862315
First received: May 20, 2013
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Intrahepatic Cholangiocarcinoma
Peripheral Cholangiocarcinoma
Cholangiolar Carcinoma
Cholangiocellular Carcinoma
Drug: Floxuridine (FUDR)
Drug: dexamethasone
Drug: Gemcitabine
Drug: Oxaliplatin
Other: MRI
Other: Research blood draws
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • progression free survival for Cohort 1 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Treatment evaluation will be done using RECIST (version 1.1)

  • progression free survival for Cohort 2 [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Treatment evaluation will be done using RECIST (version 1.1)


Secondary Outcome Measures:
  • Correlative objective of of dynamic contrast enhanced (DCE)-MRI imaging of intrahepatic cholangiocarcinoma before treatment and early during the course of treatment. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    This study will investigate DCE-MRI as potential imaging biomarkers and will measure tumor perfusion parameters and diffusion coefficients before initiating treatment and on follow-up MRI scans during treatment.

  • Correlative objective of of dynamic contrast enhanced DWI of intrahepatic cholangiocarcinoma before treatment and early during the course of treatment. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    This study will investigate diffusion weighted imaging (DWI) as potential imaging biomarkers and will measure tumor perfusion parameters and diffusion coefficients before initiating treatment and on follow-up MRI scans during treatment.


Estimated Enrollment: 86
Study Start Date: May 2013
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: No prior chemo or responded/stable with prior chemo
All patients receive HAI FUDR ([0.12 mg/kg/day X kg X pump volume] / pump flow rate)& dexamethasone (1 mg/m2/day X pump volume / 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/kg 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.
Drug: Floxuridine (FUDR) Drug: dexamethasone Drug: Gemcitabine Drug: Oxaliplatin Other: MRI Other: Research blood draws
Experimental: patients who have failed systemic therapy
All patients receive HAI FUDR ([0.12 mg/kg/day X kg X pump volume] / pump flow rate)& dexamethasone (1 mg/m2/day X pump volume / 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/kg 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.
Drug: Floxuridine (FUDR) Drug: dexamethasone Drug: Gemcitabine Drug: Oxaliplatin Other: MRI Other: Research blood draws
Experimental: pts who have had prior oxaliplatin & have existing neuropathy
All patients receive will receive gemcitabine alone with HAI FUDR/Dex Gemcitabine (800 mg/m2 IV over 30 minutes) 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.
Drug: dexamethasone Drug: Gemcitabine Other: MRI Other: Research blood draws

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 must be obtained.
  • 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 ≥ 3,000 cells/mm3
  • Platelet count ≥ 100,000/mm3
  • Creatinine ≤ 1.8 mg/dl
  • Total bilirubin < 1.6 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 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 5 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01862315

Contacts
Contact: William R. Jarnagin, MD 212-639-7601
Contact: Nancy Kemeny, MD 646-888-4180

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: William R Jarnagin, MD    212-639-7601      
Contact: Nancy Kemeny, MD    646-888-4180      
Principal Investigator: William R Jarnagin, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: William Jarnagin, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01862315     History of Changes
Other Study ID Numbers: 13-066
Study First Received: May 20, 2013
Last Updated: July 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Hepatic Arterial Infusion (HAI)
Floxuridine (FUDR)
Dexamethasone (DEX)
Gemcitabine
Oxaliplatin
13-066

Additional relevant MeSH terms:
Carcinoma
Cholangiocarcinoma
Liver Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Gemcitabine
Oxaliplatin
Floxuridine
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 28, 2014