Aprepitant Plus Granisetron and Dexamethasone for the Prevention of Vomiting in Patients With HAIC Therapy for HCC

Sponsor

Guangxi Medical University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05711823

Collaborator

(none)

300

Enrollment

Arms

10.9

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This study aims to evaluate the safety and efficacy of aprepitant combined with granisetron and dexamethasone versus granisetron and dexamethasone in the prevention of nausea and vomiting in patients with hepatocellular carcinoma (HCC) receiving hepatic arterial infusion chemotherapy (HAIC).

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: Aprepitant in combination with granisetron and dexamethasone Drug: Granisetron and dexamethasone	Phase 3

Detailed Description

FOLFOX regimen include oxaliplatin and 5-Fu. Oxaliplatin has a moderate emetic potential and 5-Fu has a low emetic potential according to European guideline for the prevention of nausea and vomiting caused by chemotherapy and radiotherapy. The Guideline recommend that patients receiving moderately emetogenic chemotherapy receive a three-drug regimen of 5-HT3, dexamethasone, and NK1-RA (aprepitant, fosaprepitant, netupitant or rolapitant). However, HAIC treatment is not through peripheral or central venous infusion of chemotherapy drugs as in other cancers, but through hepatic artery infusion of chemotherapy drugs. Chemotherapy drugs are mainly concentrated in the liver and belong to local chemotherapy, rather than systemic chemotherapy through the venous system. Therefore, although the HAIC regimen includes oxaliplatin and 5-Fu, two chemotherapeutic drugs that may cause vomiting, the literature on whether three-drug regimen is also needed to prevent vomiting has been less publicly reported. In order to further determine whether three-drug regimen is necessary, this project intends to conduct a multi-center, randomized, controlled trial to evaluate the efficacy and safety of aprepitant combined with granisetron and dexamethasone versus granisetron and dexamethasone in preventing nausea and vomiting in HCC patients receiving HAIC treatment. The results of this project will provide a reference for improving the quality of life of HCC patients during HAIC treatment, the compliance of follow-up treatment and saving medical resources.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Aprepitant in combination with Granisetron and dexamethasoneAprepitant in combination with Granisetron and dexamethasone

Masking:

Single (Outcomes Assessor)

Masking Description:

Outcome assessor do not know which patients received antiemetic therapy.

Primary Purpose:

Prevention

Official Title:

ApRepitant in Combination With Granisetron and Dexamethasone versUs Granisetron and dexamEthasone for the Prevention of Vomiting in Patients With HAIC Therapy for Hepatocellular Carcinoma: a Randomized Controlled Study (ARGUE)

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aprepitant in combination with granisetron and dexamethasone Patients with unresectable hepatocellular carcinoma will receive aprepitant in combination with granisetron and dexamethasone during the therapeutic process of hepatic arterial infusion chemotherapy.	Drug: Aprepitant in combination with granisetron and dexamethasone Patients with unresectable hepatocellular carcinoma will receive aprepitant in combination with granisetron and dexamethasone during the therapeutic process of hepatic arterial infusion chemotherapy.
Active Comparator: granisetron and dexamethasone Patients with unresectable hepatocellular carcinoma will receive granisetron and dexamethasone during the therapeutic process of hepatic arterial infusion chemotherapy.	Drug: Granisetron and dexamethasone Patients with unresectable hepatocellular carcinoma will receive granisetron and dexamethasone during the therapeutic process of hepatic arterial infusion chemotherapy.

Arm

Intervention/Treatment

Experimental: Aprepitant in combination with granisetron and dexamethasone

Patients with unresectable hepatocellular carcinoma will receive aprepitant in combination with granisetron and dexamethasone during the therapeutic process of hepatic arterial infusion chemotherapy.

Drug: Aprepitant in combination with granisetron and dexamethasone

Patients with unresectable hepatocellular carcinoma will receive aprepitant in combination with granisetron and dexamethasone during the therapeutic process of hepatic arterial infusion chemotherapy.

Active Comparator: granisetron and dexamethasone

Patients with unresectable hepatocellular carcinoma will receive granisetron and dexamethasone during the therapeutic process of hepatic arterial infusion chemotherapy.

Drug: Granisetron and dexamethasone

Patients with unresectable hepatocellular carcinoma will receive granisetron and dexamethasone during the therapeutic process of hepatic arterial infusion chemotherapy.

Outcome Measures

Primary Outcome Measures

Complete response rate [3 weeks]
Complete response rate during the first cycle defined as no emetic episodes, no rescue medication use during the first cycle of HAIC therapy.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age: 18-75 years old;
The patient is diagnosed with hepatocellular carcinoma according to the clinical diagnostic criteria of the Guideline for Diagnosis and Treatment of Primary Liver Cancer (2022 Edition) issued by the Health Commission of the People's Republic of China or confirmed by histopathology;
ECOG performance score 0 or 1;
Child-Pugh score of 5-7 (liver function);
Receiving hepatic arterial infusion chemotherapy treatment;
Expected survival time ≥6 months;
Hematological indexes should meet the following conditions: hemoglobin ≥90 g/L; Absolute neutrophil count ≥1.5×10^{9/L; Platelet ≥75×10}9/L; Total bilirubin ≤1.5×ULN; ALT≤3×ULN; AST≤3 x ULN; Alkaline phosphatase (AKP) ≤2.5×ULN; Serum albumin ≥28 g/L; Serum creatinine ≤1.5×ULN;
Urine protein <2+ or 24h urine protein quantity < 1.0g;
For women of childbearing age, contraceptive measures (such as intrauterine devices, contraceptive tablets or condoms) are required during the clinical trial until 120 days after the end of the clinical trial; Women of childbearing age had negative serum or urine HCG test results within 7 days prior to study inclusion; Male patients with fertile partners should use effective contraception during the study period and for 120 days after the study ends.

Exclusion Criteria:

Received systematic chemotherapy in the past;
The presence of congenital or acquired immunodeficiency diseases (such as HIV positive);
Active infection, or body temperature ≥ 38.5℃ or white blood cell count > 15 x 10^9/L 7 days before enrollment;
Complications of arterial or venous thrombosis, such as cerebrovascular accident, deep vein thrombosis and pulmonary infarction, etc. within 6 months;
Those who have a history of alcohol or psychotropic drug abuse and cannot quit or have mental disorders;
Pregnant or lactating women;
being treated with immunosuppressants or glucocorticoids (>10mg prednisone equal dose per day) within 2 weeks;
Previous history of motion sickness, or combined with hepatic encephalopathy or brain metastases;
Uncontrolled heart disease or symptoms (including but not limited to grade II or above heart function, unstable angina, myocardial infarction in the past 1 year, supraventricular or ventricular arrhythmias requiring treatment or intervention)