Hepatic Artery Infusion Pump for NPC Liver Metastases

Phase 1

Completed

• Conditions: Liver; Nasopharyngeal Carcinoma; Neoplasm Metastasis
• Interventions: Procedure: DSA-guided implantation of hepatic artery infusion pump; Drug: Gemcitabine; Drug: Floxuridine; Drug: dexamethasone

• Registration Number: NCT03876574
• Lead Sponsor: Xiangya Hospital of Central South University

Brief Summary

A retrospective clinical trial to study the safety and effectiveness of hepatic arterial infusion (HAI) in treating patients who have nasopharyngeal carcinoma metastatic to the liver. Hepatic-direction drug administration improves the control power for intra-hapatic lesions.

Detailed Description

OBJECTIVES:

I. Determine the safety and toxicity of hepatic arterial infusion with gemcitabine, floxuridine and dexamethasone in combination with standard treatment (radiotherapy and systemic chemotherapy) in patients with nasopharyngeal carcinoma metastases to liver.

II. Determine the objective response of intrahepatic lesions of patients treated with this regimen.

III. Determine the median survival time or overall survival time in patients treated with this regimen.

OUTLINE: This is a single-center retrospective study.

Patients receive DSA-guided implantation of HAI catheter system. HAI is initiated the next day. Gemcitabine intra-arterially for 30 minutes on day 1,8, floxuridine, dexamethasone intra-arterially continuously on days 1-14. Treatment repeats every 3 weeks in the absence of serious technical catheter-related problems, progression of intrahepatic lesions or unacceptable toxicity. Standard treatment of NPC, including radiotherapy and chemotherapy (induction chemotherapy, concurrent chemotherapy and adjuvant chemotherapy) was performed as desired.

Patients are followed every 2 HAI cycles or when necessary.

Study Timeline

• Study Start: 2011-01-01
• Primary Completion: 2017-12-31
• Study Completion: 2017-12-31
• Status Verified: 2019-02
• Study First Submitted: 2019-03-03
• Study First Submitted QC: 2019-03-12
• Last Update Submitted: 2019-03-12
• Study First Posted: 2019-03-15
• Last Update Posted: 2019-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

• Histologically confirmed nasopharyngeal carcinoma with histologically confirmed or image diagnosed metastatic to the liver
• Standard treatment of NPC, including radiotherapy and chemotherapy (induction chemotherapy, concurrent chemotherapy and adjuvant chemotherapy) is performed as desired
• Performance status - ECOG 0-2
• Absolute neutrophil count at least 1,200/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN
• No pre-existing chronic hepatic disease (chronic active hepatitis or cirrhosis)
• Creatinine no greater than ULN
• Creatinine clearance greater than 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Adequate oral nutrition (at least 1,500 calories/day)
• Able to withstand major operative procedure
• No dehydration
• No severe anorexia
• No frequent nausea or vomiting
• No prior or concurrent malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of any organ
• No prior or concurrent malignancy associated with more than 10% probability of death from malignant disease within 5 years of diagnosis
• No concurrent immunotherapy
• No concurrent colony-stimulating factors during the first course of study therapy
• No more than 1 prior adjuvant systemic fluorouracil (5-FU) regimen with or without levamisole, leucovorin calcium, or irinotecan
• No prior hepatic artery infusion therapy with 5-FU or floxuridine
• No prior systemic chemotherapy for metastatic disease
• No prior or concurrent sorivudine or brivudine

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	DSA-guided implantation of hepatic artery infusion pump	Patients undergo DSA-guided implantation of hepatic artery infusion pump. All patients receive the intervention "Hepatic artery infusion of gemcitabine and floxuridine" the next day after pump implantation. The HAI therapy is initiated on day 1, 8: Gemcitabine 1g/m2 for 30 minutes, followed by a blended solution which comprised floxuridine (FUDR) at 0.15 mg/kg/day, dexa-methasone (DXM) at 1 mg/m2/day, low molecular heparin 3200U and saline, lasted for 7 days continuously.Standard treatments of NPC, including radiotherapy and chemotherapy (induction chemotherapy, concurrent chemotherapy and adjuvant chemotherapy) are performed as desired.
Treatment	Gemcitabine	Patients undergo DSA-guided implantation of hepatic artery infusion pump. All patients receive the intervention "Hepatic artery infusion of gemcitabine and floxuridine" the next day after pump implantation. The HAI therapy is initiated on day 1, 8: Gemcitabine 1g/m2 for 30 minutes, followed by a blended solution which comprised floxuridine (FUDR) at 0.15 mg/kg/day, dexa-methasone (DXM) at 1 mg/m2/day, low molecular heparin 3200U and saline, lasted for 7 days continuously.Standard treatments of NPC, including radiotherapy and chemotherapy (induction chemotherapy, concurrent chemotherapy and adjuvant chemotherapy) are performed as desired.
Treatment	Floxuridine	Patients undergo DSA-guided implantation of hepatic artery infusion pump. All patients receive the intervention "Hepatic artery infusion of gemcitabine and floxuridine" the next day after pump implantation. The HAI therapy is initiated on day 1, 8: Gemcitabine 1g/m2 for 30 minutes, followed by a blended solution which comprised floxuridine (FUDR) at 0.15 mg/kg/day, dexa-methasone (DXM) at 1 mg/m2/day, low molecular heparin 3200U and saline, lasted for 7 days continuously.Standard treatments of NPC, including radiotherapy and chemotherapy (induction chemotherapy, concurrent chemotherapy and adjuvant chemotherapy) are performed as desired.
Treatment	dexamethasone	Patients undergo DSA-guided implantation of hepatic artery infusion pump. All patients receive the intervention "Hepatic artery infusion of gemcitabine and floxuridine" the next day after pump implantation. The HAI therapy is initiated on day 1, 8: Gemcitabine 1g/m2 for 30 minutes, followed by a blended solution which comprised floxuridine (FUDR) at 0.15 mg/kg/day, dexa-methasone (DXM) at 1 mg/m2/day, low molecular heparin 3200U and saline, lasted for 7 days continuously.Standard treatments of NPC, including radiotherapy and chemotherapy (induction chemotherapy, concurrent chemotherapy and adjuvant chemotherapy) are performed as desired.

Primary Outcome Measures

Name	Time	Method
Disease control rate (DCR) of intrahepatic lesions	2 years	Assess the Disease control rate (DCR) of intrahepatic lesions by enhanced spiral-CT scan according to RECIST criteria.

Secondary Outcome Measures

Name	Time	Method
Side effects and adverse events	2 years	To determine the safety and tolerability of HAI for NPC liver metastases by establishing the rates of toxicity
Overall survival time	7 years	From the date of HAI catheter implantation to the date of death from any cause or to completion of trial, whichever comes first, up to 84 months.