mFOLFIRINOX Followed by Hepatic Arterial Infusion of Floxuridine and Dexamethasone With Systemic mFOLFIRI for Unresectable Liver-dominant Intrahepatic Cholangiocarcinoma

NCT04251715 | Active Not Recruiting Phase 2 DMC FDA Drug FDA Device

• 3 other identifiers: STUDY00016033NCI-2020-00477HELIX-1
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the efficacy and safety of systemic induction of mFOLFIRINOX, followed by hepatic arterial infusion (HAI) floxuridine-dexamethasone administered concurrently with systemic mFOLFIRI in treating patients with liver-dominant intrahepatic cholangiocarcinoma (ICC) that cannot be removed by surgery (unresectable). Drugs used in chemotherapy regimens, such as mFOLFIRINOX and mFOLFIRI (Oxaliplatin, Irinotecan, Fluorouracil, Folinic acid, Floxuridine) work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Delivering chemotherapy via HAI (hepatic arterial infusion) can allow for liver-directed treatment while limiting toxic side effects typically seen with traditional chemotherapy.

Conditions

Liver and Intrahepatic Bile Duct Carcinoma; Stage III Intrahepatic Cholangiocarcinoma AJCC v8; Stage IIIA Intrahepatic Cholangiocarcinoma AJCC v8; Stage IIIB Intrahepatic Cholangiocarcinoma AJCC v8; Stage IV Intrahepatic Cholangiocarcinoma AJCC v8; Unresectable Intrahepatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of abnormal liver function

  Defined by unacceptable elevation in liver enzymes, or radiographic evidence of biliary sclerosis on computed tomography (CT)/magnetic resonance imaging (MRI) (as measured following the completion of 2 cycles of hepatic arterial infusion \[HAI\] in Treatment Period 2).

  Up to 2 years

• Disease control rate (DCR) - during HAI+SYS

  DCR is defined as the percentage of patients who have achieved complete response (CR), partial response (PR), or stable disease (SD). Measured from beginning of Treatment Period 2 to end of Treatment Period 2 during treatment with HAI + systemic chemotherapy (SYS).

  Up to 2 years

Secondary Outcomes (8)

• DCR - entire treatment

  Up to 2 years

• DCR - FOLFIRINOX

  Up to 1 year

• Progression free survival (PFS) - FOLFIRINOX

  Up to 1 year

• PFS

  Up to 2 years

• Overall response rate (ORR)

  Up to 2 years

Study Arms (1)

mFOLFIRINOX, Floxuridine-DEX, mFOLFIRI

EXPERIMENTAL

Treatment Period 1 - mFOLFIRINOX for 4 cycles (cycle = 14 days) Cycle 1 * Oxaliplatin 85 mg/m2 intravenously (iv) over 2 hours * Folinic acid 400 mg/m2 iv over 2 hours * Irinotecan 165 mg/m2 iv over 90 minutes * Fluorouracil 400 mg/m2 iv bolus after folinic acid * Fluorouracil 2,400 mg/m2 continuous infusion over 46 hours Dosages on Cycle 2, 3, and 4 will be reduced by 25% Treatment Period 2 - HAI delivery of floxuridine + mFOLFIRI for 2 cycles (cycle = 28 days) * Floxuridine-DEX (with heparin and saline) - 0.12 mg/kg/day; via HAI pump, adjusted for weight and flow rate mFOLFIRI on Day 15 * Irinotecan 180 mg/m2 iv over 30 minutes to 1 hour * Folinic acid 400mg/m2 iv over 30 minutes to 1 hour * 5-FU 1000 mg/m2 continuous infusion over 46 hours

Drug: Dexamethasone; Drug: Floxuridine; Device: Implanted Medical Device; Drug: Irinotecan; Drug: Leucovorin; Drug: Oxaliplatin; Other: Quality-of-Life Assessment

Interventions

Dexamethasone DRUG

Given intraarterially via HAI pump

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

mFOLFIRINOX, Floxuridine-DEX, mFOLFIRI

Floxuridine DRUG

Given intraarterially via HAI pump

Also known as: 2''-Deoxy-5-fluorouridine, 5-Fluoro-2''-deoxyuridine, 5-Fluorodeoxyuridine, 5-Fluorouracil deoxyriboside, 5-FUdR, FDUR, Floxuridin, Fluorodeoxyuridine, Fluorouridine Deoxyribose, Fluoruridine Deoxyribose, FUdR, WR-138720

mFOLFIRINOX, Floxuridine-DEX, mFOLFIRI

Implanted Medical Device DEVICE

Implanted hepatic arterial infusion pump by surgical oncology, to deliver HAI therapy

Also known as: IMPLANTED

mFOLFIRINOX, Floxuridine-DEX, mFOLFIRI

Irinotecan DRUG

Given IV

mFOLFIRINOX, Floxuridine-DEX, mFOLFIRI

Leucovorin DRUG

Given IV

Also known as: Folinic acid

mFOLFIRINOX, Floxuridine-DEX, mFOLFIRI

Oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

mFOLFIRINOX, Floxuridine-DEX, mFOLFIRI

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

mFOLFIRINOX, Floxuridine-DEX, mFOLFIRI

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed intrahepatic cholangiocarcinoma (ICC; also variously reported as peripheral cholangiocarcinoma, cholangiolar carcinoma or cholangiocellular carcinoma) with confirmation of the pathologic diagnosis at Oregon Health \& Science University (OHSU)
• Surgically unresectable liver-dominant ICC, or multifocal ICC considered surgically unresectable or resection is contraindicated
• For liver-dominant ICC, disease must comprise \< 70% of the liver parenchyma, as defined by computed tomography (CT) liver segmental volumetrics
• Limited extrahepatic disease
• Clinical or radiographic evidence of metastatic disease to regional lymph nodes and limited extrahepatic disease to the lungs is permitted at the discretion of the principal investigator (PI)
• Radiographically measurable hepatic disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria
• Disease must be considered technically unresectable at the time of preoperative evaluation or radiographically multifocal as determined by hepatobiliary surgical oncologists
• Participants should be treatment naive. Those previously treated with systemic chemotherapy (e.g., gemcitabine, cisplatin, or other investigational agents) may be eligible at the discretion of the PI
• Participants with an Eastern Cooperative Oncology Group (ECOG) 0 or 1 status (Karnofsky \>= 60), and can be considered candidates for general anesthesia, abdominal exploration and hepatic artery pump placement
• Participants with treated chronic hepatitis (e.g., treated hepatitis B virus \[HBV\], treated hepatitis C virus \[HCV\]) are eligible, but must be Child-Pugh class A
• White blood cell (WBC) \>= 3000 cells/mm\^3
• Absolute neutrophil count (ANC) \>= 1500 cells/mm\^3
• Platelet count \>= 100,000/mm\^3
• International normalized ratio (INR) =\< 1.5
• Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR creatinine clearance \>= 40 ml/min (\> 0.675 ml/sec) using Cockcroft-Gault equation

You may not qualify if:

• Presence of extensive or multifocal metastatic extrahepatic or peritoneal disease. Clinical or radiographic evidence of metastatic disease to regional lymph nodes will be allowed, as will limited pulmonary disease at the discretion of the OHSU PI
• Prior treatment with floxuridine, oxaliplatin, or irinotecan
• Prior treatment with hepatic arterial infusion therapy
• Known to have experienced an allergic reaction or other signs of intolerance to implanted devices
• Body size that is insufficient to accommodate the physical size of the pump
• Diagnosis of sclerosing cholangitis
• Diagnosis of hepatic encephalopathy
• Clinical evidence of portal hypertension (ascites, gastroesophageal varices, or portal vein thrombosis) or hepatic venous wedge pressures \> 8 mmHg if available
• History of multiple abdominal operations that would preclude HAI pump placement
• Active infection
• Current biliary obstruction requiring placement of endoscopic or transhepatic stents for biliary decompression
• Presence of aberrant or replaced hepatic arterial anatomy not amenable to placement of a hepatic arterial infusion pump catheter as judged by the operating surgeon
• History of peripheral neuropathy \> grade 1
• Allergies to iodine contrast medium, that cannot be premedicated with steroids per institutional radiology guidelines (e.g., dexamethasone)
• Uncontrolled severe coagulation disorders (INR \> 1.5 in patients not on warfarin therapy)

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Related Publications (1)

• Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.

  PMID: 15273542 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Cholangiocarcinoma

Interventions

Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Floxuridine; 5-fluoro-2'-deoxyuridine; Irinotecan; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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; Deoxyuridine; Uridine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes

Study Officials

• Skye C Mayo, MD, MPH

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 30, 2020
• First Posted: February 5, 2020
• Study Start: April 28, 2021
• Primary Completion: June 30, 2025
• Study Completion: November 30, 2025
• Last Updated: April 18, 2025

Record last verified: 2025-04

Locations

US (1)