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

NCT01525069 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 201111068
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Cholangiocarcinoma; Liver Neoplasms

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Time to progression (TTP)

  12 months

• Response rates

  8 weeks

• Overall survival

  12 months

• Number and grade of adverse events

  Beginning with pump placement and continuing for 30 days following the last day of study treatment (median length of treatment 3 months)

• Imaging biomarkers of tumor response

  Pre-treatment and then every 8 weeks during treatment (median length of treatment 3 months)

Study Arms (3)

Arm A (HAI FUDR alone)

EXPERIMENTAL

* 14-42 days after surgery for insertion of the HAI pump, floxuridine (FUDR) and dexamethasone plus heparin in normal saline to a total volume of 30 ml will be administered through the HAI pump. * This will be repeated on Day 1 of each 28 day cycle. FUDR administration will be a 14-day continuous infusion using the HAI pump. * The pump will be emptied and refilled with heparinized normal saline and dexamethasone on Day 15 of each cycle to be infused over the next 14 days.

Drug: Floxuridine; Drug: Dexamethasone

Arm B (HAI FUDR + gemcitabine)

EXPERIMENTAL

* Consists of Cohort B1, B2, and B3. Enrollment to specific cohorts will depend on the number of DLTs in each cohort. Each cohort has a different dose of FUDR and gemcitabine. * Gemcitabine IV will be given on Days 1, 8, and 15 of each 28 day cycle in Cohort B1 * Gemcitabine IV will be given on Days 1 and 15 of each 28 day cycle in Cohort B2 \& B3 * 14-42 days after surgery for insertion of the HAI pump, floxuridine (FUDR) and dexamethasone plus heparin in normal saline to a total volume of 30 ml will be administered through the HAI pump. * This will be repeated on Day 1 of each 28 day cycle. FUDR administration will be a 14-day continuous infusion using the HAI pump. * The pump will be emptied and refilled with heparinized normal saline and dexamethasone on Day 15 of each cycle to be infused over the next 14 days.

Drug: Floxuridine; Drug: Dexamethasone; Drug: Gemcitabine

Arm C (HAI FUDR + gemcitabine + oxaliplatin)

EXPERIMENTAL

* Consists of Cohort C1, C2, C3, and C4. Enrollment to specific cohorts will depend on the number of DLTs in each cohort. Each cohort has a different dose of FUDR, gemcitabine, and oxaliplatin. * Gemcitabine IV will be given on Days 1 and 15 of each 28 day cycle. * Oxaliplatin IV will be given on Days 1 and 15 of each 28 days cycle. * 14-42 days after surgery for insertion of the HAI pump, floxuridine (FUDR) and dexamethasone plus heparin in normal saline to a total volume of 30 ml will be administered through the HAI pump. * This will be repeated on Day 1 of each 28 day cycle. FUDR administration will be a 14-day continuous infusion using the HAI pump. * The pump will be emptied and refilled with heparinized normal saline and dexamethasone on Day 15 of each cycle to be infused over the next 14 days.

Drug: Floxuridine; Drug: Dexamethasone; Drug: Gemcitabine; Drug: Oxaliplatin

Interventions

Floxuridine DRUG

Also known as: 5-FUDR, FdUrD, floxuridin, fluorodeoxyuridine, fluoruridine deoxyribose, FUdR

Arm A (HAI FUDR alone); Arm B (HAI FUDR + gemcitabine); Arm C (HAI FUDR + gemcitabine + oxaliplatin)

Dexamethasone DRUG

Also known as: Aeroseb-Dex, Decaderm, Decadron, Decaspray, DM, DXM

Arm A (HAI FUDR alone); Arm B (HAI FUDR + gemcitabine); Arm C (HAI FUDR + gemcitabine + oxaliplatin)

Gemcitabine DRUG

Also known as: dFdC, dFdCyd, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar, LY-188011

Arm B (HAI FUDR + gemcitabine); Arm C (HAI FUDR + gemcitabine + oxaliplatin)

Oxaliplatin DRUG

Also known as: 1-OHP, Dacotin, Dacplat, diaminocyclohexane oxalatoplatinum, Eloxatin, L-OHP

Arm C (HAI FUDR + gemcitabine + oxaliplatin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (5)

• 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

  BACKGROUND

• 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.

  PMID: 18534963 BACKGROUND

• 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.

  PMID: 19470932 BACKGROUND

• 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.

  PMID: 15716576 BACKGROUND

• 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.

  PMID: 19491285 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Cholangiocarcinoma; Liver Neoplasms

Interventions

Floxuridine; Dexamethasone; Calcium Dobesilate; Gemcitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Deoxyuridine; Uridine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Deoxycytidine; Cytidine; Coordination Complexes

Study Officials

• William Chapman, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2012
• First Posted: February 2, 2012
• Study Start: April 3, 2012
• Primary Completion: August 8, 2018
• Study Completion: August 2, 2022
• Last Updated: August 10, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)