A Prospective, Multicenter, Phase III Clinical Study Comparing Continuous Hepatic Arterial Infusion of Raltetrexed With Oxaliplatin(SALOX) Versus FOLFOX in Advanced Hepatocellular Carcinoma
Overview
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Sun Yat-sen University
- Enrollment
- 426
- Locations
- 1
- Primary Endpoint
- Two-years progression-free survival rate
Overview
Brief Summary
Hepatic artery infusion chemotherapy (HAIC) have shown promising outcomes in patients with advanced hepatocellular carcinoma (HCC).In China, Oxaliplatin combined with 5-fluorouracil is commonly used in continuous hepatic arterial perfusion chemotherapy.But the 5-FU requiring a long infusion and Calcium folate is also needed to sensitize 5-FU. Moreover, 5-FU regimen was associated with a variety of adverse events, which limited its application in HAIC.Compared to 5-fluorouracil, raltetrexed is less toxic, has a stronger anti-tumor effect and can be administered in just two to three hours. However, the comparison of the two drugs in HAIC to treat advanced HCC has not been reported. In this study, we will evaluate the the progression-free survival(PFS)、objective response rate（ORR）、 disease vacancy rate（DCR）、overall survival (OS) and safety in patients with advanced hepatocellular carcinoma (Ad-HCC) who are undergoing hepatic arterial infusion (HAI) of Raltetrexed plus oxaliplatin (SALOX) compared with oxaliplatin, fluorouracil/leucovorin (FOLFOX) treatment by designing prospective, multi-center phase III clinical study.
Detailed Description
Femoral artery puncture and catheterization were performed in every cycle of treatment,a micro-catheter was inserted and located in feeding hepatic artery. The therapeutic scheme was that, the experimental group SALOX regimen including oxaliplatin (130 mg/m2 infusion for 3 hours on day 1) and raltetrexed (2mg/m2 for 30 to 60 minutes on day 1) . The control group modified FOLFOX6 regimens including oxaliplatin (130 mg/m2 infusion for 3 hours on day 1), leucovorin (200 mg/m2 from hour 3 to 5 on day 1) and Fluorouracil (400 mg/m2 in bolus, and then 2,400 mg/m2 continuous infusion 46 hours). All chemo-drugs were given by HAI. Treatment was repeated every 3 weeks and continued until intrahepatic lesions progression or unacceptable toxicity.Enhanced CT or MRI was performed every 6 weeks after treatment begins. Routine follow-up intervals were 2-4 months.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Masking Description
Oxaliplatin Fluorouracil
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Provision of signed and dated, written informed consent form (ICF) and any locally required authorization obtained from the patient prior to any mandatory study specific procedures, sampling, and analyses.
- •Provision of signed and dated written genetic informed consent prior to optional collection of sample for genetic analysis.
- •Patients with BCLC stage C hepatocellular carcinoma confirmed by pathology or clinically diagnosed
- •Age ≥18 years and \< 75 years at the time of screening.
- •Portal vein invasion or extrahepatic oligosaccharides were detected by baseline imaging. Oligosaccharides were defined as no more than two extrahepatic organs and no more than three tumors.
- •Child-Pugh score class A to B
- •No local antitumor therapy for hepatocellular carcinoma was received within 4 weeks prior to enrollment
- •No previous systemic antitumor therapy for hepatocellular carcinoma
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
- •The expected survival time is no less than 3 months
Exclusion Criteria
- •A history of liver decompensation, such as refractory ascites, gastrointestinal bleeding, or hepatic encephalopathy; Uncontrolled complications, including but not limited to: Persistent or activity (except the HBV and HCV) infection, symptoms of congestive heart failure and uncontrolled diabetes, uncontrolled hypertension, unstable angina, uncontrolled arrhythmias, active ILD, severe chronic GI disease accompanied by diarrhea, or compliance with requirements may limit the research, resulted in significant increase risk of AE or influence Subjects provided psychiatric/social problem status on their ability to provide written informed consent.A history of active primary immunodeficiency or human immunodeficiency virus; Active or previous records of autoimmune disease or inflammatory diseases, including inflammatory bowel disease (e.g., colitis or crohn's disease\], diverticulitis, except \[diverticulosis\], systemic lupus erythematosus (sle), sarcoidosis syndrome or wegener syndrome (e.g., granulomatous vasculitis, gray's disease, rheumatoid arthritis, the pituitary gland inflammation and uveitis\]).
- •Known to produce allergic or hypersensitive reactions to any study drug or any excipient thereof;
- •Significant clinical gastrointestinal bleeding or a potential risk of bleeding was identified by the investigator during the 30 days prior to study entry.
- •Tumors of the central nervous system, including metastatic brain tumors;
- •Pregnant women or breast-feeding patients;
- •Complicated with other malignant tumors:
- •Malignant tumors that have been treated for therapeutic purposes, have no known active disease for ≥5 years prior to the first administration of the study drug, and have a low potential risk of recurrence
- •Fully treated non-melanoma skin cancer or malignant freckle moles with no evidence of disease
- •Fully treated carcinoma in situ without evidence of disease
- •Prior to the initial dosing of the study drug, they had received anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy
Outcomes
Primary Outcomes
Two-years progression-free survival rate
Time Frame: Two years
It is defined as the percentage of patients who achieve a time interval of two years of no disease progression (i.e., intrahepatic recurrence or extrahepatic metastasis) or death (by any cause) from date of enrollment, whichever occurs first.
Secondary Outcomes
- Two-years Overall Survival Rate(Two years)
- Evaluate the patient's cancer-related QoL using the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire (QLQ), the EORTC QLQ-C30.(From date of randomization up to two years, approximately)
- Evaluate the patient's cancer-related QoL using the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire (QLQ), the EORTC QLQ-HCC18.(From date of randomization up to two years, approximately)
- Objective response rate(Two years)
Investigators
Ming Zhao
Associate Director of Minimally Invasive Intervention
Sun Yat-sen University