A Phase III Randomized Trial of Comparison of Survival Benefit of Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil/Leucovorin With Sorafenib for Patients With Barcelona-Clinic Liver Cancer (BCLC)-C Stage Hepatocellular Carcinoma
Overview
- Phase
- Phase 3
- Intervention
- FOLFOX regimen
- Conditions
- Liver Cancer
- Sponsor
- Sun Yat-sen University
- Enrollment
- 262
- Locations
- 1
- Primary Endpoint
- Overall survival
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This trial was designed to investigate whether the survival outcome, response rate and safety of hepatic arterial infusion of oxaliplatin, fluorouracil/leucovorin regimens for patients with Barcelona-Clinic Liver Cancer (BCLC)-C stage hepatocellular carcinoma was superior than those of the standard treatment with sorafenib or not.
Detailed Description
Hepatocellular carcinoma is the fifth most common malignancy worldwide. Advanced-stage disease is found in 25%-70% of HCC at diagnosis, with a median survival time of only 4.2-7.9 months due to limited treatment options. To date, sorafenib is the only standard treatment shown to extend overall survival for advanced hepatocellular carcinoma (Ad-HCC). However, low response rates, modest survival advantages and high-level heterogeneity of individual response, such limitations of sorafenib prohibit its widespread use in Ad-HCC and more alternative therapies are highly required at present. Hepatic arterial infusion chemotherapy (HAIC) can provide chemotherapeutic agents to liver at higher concentration with lower toxicity and has been reported favorable results in advanced HCC. However, HAIC provides good but variable outcomes, with a response rate of 7-81% and median survival time of 6-15.9 months. The unstable response may attribute to complicate combinations based on various drugs, including fluorouracil (5-FU), cisplatin, doxorubicin, mitomycin, leucovorin and interferon. FOLFOX (oxaliplatin, 5-FU/leucovorin) was a regimen first used in colon cancer with liver metastasis and reported to be effective both by systemic and HAIC in amounts of clinical trials. A recent phase II study has shown that HAI of FOLFOX (HAIF) was well tolerated and effective in Ad-HCC. To the investigator's knowledge, no clinical studies have been developed on comparing the survival benefit of HAIF with sorafenib for patients with Ad-HCC. In this phase III trial, the investigators aimed to compare survival outcome, response rate and safety of HAIF with sorafenib in patients with Ad-HCC.
Investigators
Ming Zhao
Professor
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •Written informed consent must be obtained prior to any screening procedures.
- •Cytohistological confirmation is required for diagnosis of HCC.
- •Patients with advanced (unresectable and/or metastatic, stage C based on Barcelona-Clinic Liver Cancer \[BCLC\] staging classification) hepatocellular carcinoma which would not be suitable for treatment with loco-regional therapies or have progressed following locoregional therapy such as surgical resection, percutaneous hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy.
- •At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.
- •Lesions previously treated with local therapy, such as radiation therapy, hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy should not be selected unless progression is noted at baseline, in which case, these lesions would be considered as non-target lesions.
- •Current cirrhotic status of Child-Pugh class A-B, with no encephalopathy. Ascites controlled by diuretics is permitted in this study.
- •Availability of a representative tumor tissue specimen (archival tumor tissue is allowed) at pre-screening.
- •Eastern Cooperative Oncology Group Scale for Assessment of Patient Performance Status ≤
- •Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 4 weeks after the completion of trial.
- •Adequate bone marrow, liver and renal function as assessed by central lab by means of the following laboratory requirements from samples within 7 days prior to procedure:
Exclusion Criteria
- •Received any prior systemic chemotherapy or molecular-targeted therapy for HCC such as sorafenib.
- •Previous local therapy completed less than 4 weeks prior to the dosing and, if present any related acute toxicity \> grade
- •Any contraindications for hepatic arterial infusion procedure:
- •Impaired clotting test (platelet count \< 60000/mm3, prothrombin activity \< 50%).
- •Renal failure / insufficiency requiring hemo-or peritoneal dialysis.
- •Known severe atheromatosis.
- •Known uncontrolled blood hypertension (\> 160/100 mm/Hg).
- •Patients with any other malignancies within the last 3 years before study start.
- •History of HCC tumor rupture.
- •Patients with severe encephalopathy.
Arms & Interventions
HAIF group
FOLFOX regimen: oxaliplatin 130 mg/m2 on day 1 from hour 0 to 3; leucovorin 200 mg/m2 from hour 3 to 5, fluorouracil 400 mg/m2 bolus at hour 5, and then fluorouracil 2,400 mg/m2 over 46 hours, via hepatic artery, once every 3 weeks.
Intervention: FOLFOX regimen
Sorafenib group
Sorafenib 200mg Tab, 400 mg twice per day orally. Treatment was given in 4-week cycles.
Intervention: Sorafenib 200Mg Tab
Outcomes
Primary Outcomes
Overall survival
Time Frame: 1 months
Overall survival was the length of time after treatment until death from any cause.
Secondary Outcomes
- Time to Progression(1 months)
- Time to Intrahepatic tumor Progression(1 months)