Hepatic Arterial Infusion in Treating Patients With Locally Advanced, Non-Metastatic Cholangiocarcinoma

Cholangiocarcinoma Clinical Trial

Official title:

Pilot Study of Hepatic Arterial Infusion Therapy in Patients With Unresectable or Borderline Resectable Intrahepatic Cholangiocarcinoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01525069
• Other study ID #: 201111068
• Status: Terminated
• Phase: Phase 1
• Start date: April 3, 2012
• Est. completion date: August 2, 2022

Study information

• Verified date: August 2022
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 27
• Est. completion date: August 2, 2022
• Est. primary completion date: August 8, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Liver Neoplasms

Intervention

Drug:
• Floxuridine

• Dexamethasone

• Gemcitabine

• Oxaliplatin

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (5)

Jarnagin WR, Schwartz LH, Gultekin DH, Gönen 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. — View Citation

Kemeny NE, Gonen M. Hepatic arterial infusion after liver resection. N Engl J Med. 2005 Feb 17;352(7):734-5. — View 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. — View 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. — View 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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicities (DLTs)	Document the frequency of grades 3-5 non-hematologic toxicities (dose-limiting toxicities) associated with the treatment regimen by patient and by type of toxicity for each cohort during the first 2 cycles of treatment	Completion of 2 cycles of treatment by all patients (approximately 4 years)
Secondary	Time to progression (TTP)	Describe median time to progression with a 95% confidence interval for each cohort.	12 months
Secondary	Response rates	The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started); Using RECIST 1.1	8 weeks
Secondary	Overall survival		12 months
Secondary	Number and grade of adverse events	Determine safety, tolerability and toxicities based on the number and grade of adverse events associated with this regimen.	Beginning with pump placement and continuing for 30 days following the last day of study treatment (median length of treatment 3 months)
Secondary	Imaging biomarkers of tumor response	Using magnetic resonance diffusion-weighted imaging (DW-MRI) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) before and during the course of treatment with HAI therapy, validate imaging biomarkers of tumor response	Pre-treatment and then every 8 weeks during treatment (median length of treatment 3 months)
Secondary	Overall survival		Up to 5 years
Secondary	Time to progression (TTP)	Describe median time to progression with a 95% confidence interval for each cohort.	24 months

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine