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

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ClinicalTrials.gov Identifier: NCT01862315
Recruitment Status : Active, not recruiting
First Posted : May 24, 2013
Last Update Posted : May 6, 2019
Sponsor:
Collaborators:
Ohio State University
University of Texas
Washington University School of Medicine
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE May 20, 2013
First Posted Date  ICMJE May 24, 2013
Last Update Posted Date May 6, 2019
Study Start Date  ICMJE May 2013
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2015)
  • progression free survival for Cohort 1 [ Time Frame: 6 months ]
    Treatment evaluation will be done using RECIST (version 1.1)
  • progression free survival for Cohort 2 [ Time Frame: 3 months ]
    Treatment evaluation will be done using RECIST (version 1.1)
  • response for Cohort 3 [ Time Frame: 6 months ]
    Treatment evaluation will be done using RECIST (version 1.1)
Original Primary Outcome Measures  ICMJE
 (submitted: May 22, 2013)
progression free survival [ Time Frame: 6 months ]
Treatment evaluation will be done using RECIST (version 1.1)
Change History Complete list of historical versions of study NCT01862315 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2013)
  • 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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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)
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Intrahepatic Cholangiocarcinoma
  • Peripheral Cholangiocarcinoma
  • Cholangiolar Carcinoma
  • Cholangiocellular Carcinoma
Intervention  ICMJE
  • Drug: Floxuridine (FUDR)
  • Drug: dexamethasone
  • Drug: Gemcitabine
  • Drug: Oxaliplatin
  • Other: MRI
  • Other: Research blood draws
    These are optional
Study Arms  ICMJE
  • Experimental: No prior chemo or responded/stable with prior chemo
    All patients receive HAI FUDR ([0.12 mg/kg/day kg 30] / pump flow rate)& dexamethasone ({1 mg/m2/day30} 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/m2 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.
    Interventions:
    • 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 kg 30] / pump flow rate)& dexamethasone ({1 mg/m2/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. All patients receive Gemcitabine (800 mg/m2 IV over 30 minutes) & Oxaliplatin (85 mg/m2 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.
    Interventions:
    • 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) alone 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.
    Interventions:
    • Drug: dexamethasone
    • Drug: Gemcitabine
    • Other: MRI
    • Other: Research blood draws
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 25, 2019)
55
Original Estimated Enrollment  ICMJE
 (submitted: May 22, 2013)
36
Estimated Study Completion Date  ICMJE May 2020
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01862315
Other Study ID Numbers  ICMJE 13-066
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE
  • Ohio State University
  • University of Texas
  • Washington University School of Medicine
Investigators  ICMJE
Principal Investigator: William Jarnagin, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP