Clinical trial NCT01525069: Hepatic Arterial Infusion in Treating Patients With Locally Advanced, Non-Metastatic Cholangiocarcinoma
Official title: Pilot Study of Hepatic Arterial Infusion Therapy in Patients With Unresectable or Borderline Resectable Intrahepatic Cholangiocarcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Cholangiocarcinoma
Liver Neoplasms
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2012-02-02
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This pilot clinical trial studies the safety and effectiveness of continuous hepatic arterial infusion (HAI) of floxuridine (FUDR) alone or in combination with other chemotherapeutic drugs in treating patients with locally advanced cholangiocarcinoma that cannot be removed by surgery. HAI is a method to deliver higher concentrations of FUDR more directly to liver tumors and reduces side effects. HAI alone or in combination with oxaliplatin and/or gemcitabine may significantly improve clinical outcomes of patients with locally advanced cholangiocarcinoma.


Eligibility criteria: Inclusion Criteria:

* Patient must have suspected intrahepatic or hilar cholangiocarcinoma with minimal extrahepatic disease. Diagnosis must be histologically or cytologically confirmed for continued treatment on study after pump placement.
* Patient must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan/MRI
* Patient must have disease that is unresectable or borderline resectable with \< 70% liver involvement by cancer
* Patient must be \>= 18 years old.
* Patient's Eastern Cooperative Oncology Group (ECOG) performance status must be =\< 2 (Karnofsky \>= 60%)
* Patient must have normal organ and marrow function as defined below:

  * Absolute neutrophil count \>= 1,500/mcL
  * Platelets \>= 75,000/mcL
  * Total bilirubin =\< 2 mg/dL
  * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 5 X institutional upper limit of normal
  * Creatinine \<= institutional upper limit normal
* Patient must be able to understand and willing to sign a written informed consent document

Exclusion Criteria:

* Patients must not have had prior treatment with FUDR
* Patient must not be receiving any other investigational agents
* Patient must not have a diagnosis of Gilbert's disease
* Patient must not have a diagnosis of hepatic encephalopathy
* Patient must not have had prior external beam radiation to the liver
* Patient must not have a diagnosis of sclerosing cholangitis
* Patient must not have any uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Patient must not be pregnant or breastfeeding

Primary outcomes:
measure: Dose-limiting toxicities (DLTs)
timeFrame: Completion of 2 cycles of treatment by all patients (approximately 4 years)
Secondary outcomes:
measure: Time to progression (TTP)
timeFrame: 12 months
measure: Response rates
timeFrame: 8 weeks
measure: Overall survival
timeFrame: 12 months
measure: Number and grade of adverse events
timeFrame: Beginning with pump placement and continuing for 30 days following the last day of study treatment (median length of treatment 3 months)
measure: Imaging biomarkers of tumor response
timeFrame: Pre-treatment and then every 8 weeks during treatment (median length of treatment 3 months)
measure: Overall survival
timeFrame: Up to 5 years
measure: Time to progression (TTP)
timeFrame: 24 months
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: William Chapman, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Valle JW WH, Palmer DD, Cunningham D, Anthoney DA, Maraveyas A, Hughes SK, Roughton JA, Bridgewater JA: Gemcitabine with or without cisplatin in patients (pts) with advanced or metastatic biliary tract cancer (ABC): Results of a multicenter, randomized phase III trial (the UK ABC-02 trial). J Clin Oncol 27:15s, 2009 (suppl, abstr 4503), 2009
citation: Tan BR, Brenner WS, Picus J, Marsh S, Gao F, Fournier C, Fracasso PM, James J, Yen-Revollo JL, McLeod HL. Phase I study of biweekly oxaliplatin, gemcitabine and capecitabine in patients with advanced upper gastrointestinal malignancies. Ann Oncol. 2008 Oct;19(10):1742-8. doi: 10.1093/annonc/mdn375. Epub 2008 Jun 4.
citation: Kemeny NE, Melendez FD, Capanu M, Paty PB, Fong Y, Schwartz LH, Jarnagin WR, Patel D, D'Angelica M. Conversion to resectability using hepatic artery infusion plus systemic chemotherapy for the treatment of unresectable liver metastases from colorectal carcinoma. J Clin Oncol. 2009 Jul 20;27(21):3465-71. doi: 10.1200/JCO.2008.20.1301. Epub 2009 May 26.
citation: Kemeny NE, Gonen M. Hepatic arterial infusion after liver resection. N Engl J Med. 2005 Feb 17;352(7):734-5. doi: 10.1056/NEJM200502173520723. No abstract available.
citation: Jarnagin WR, Schwartz LH, Gultekin DH, Gonen M, Haviland D, Shia J, D'Angelica M, Fong Y, DeMatteo R, Tse A, Blumgart LH, Kemeny N. Regional chemotherapy for unresectable primary liver cancer: results of a phase II clinical trial and assessment of DCE-MRI as a biomarker of survival. Ann Oncol. 2009 Sep;20(9):1589-1595. doi: 10.1093/annonc/mdp029. Epub 2009 Jun 2.