Phase 2 Study of Sorafenib Plus HAIC of FOLFOX vs. Sorafenib Plus HAIC of OXA for Advanced HCC

• ClinicalTrials.gov Identifier: NCT03812770
• Recruitment Status: Unknown
• First Posted: January 23, 2019
• Last Update Posted: April 17, 2019
• Sponsor: Sun Yat-sen University
• Collaborators: Kaiping Central Hospital; Guangzhou No.12 People's Hospital
• Information provided by (Responsible Party): Shi Ming, Sun Yat-sen University

Study Description

Brief Summary:

The purpose of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin plus fluorouracil/leucovorin compared with HAIC of oxaliplatin alone in patients with advanced hepatocellular carcinoma (HCC)

Condition or disease	Intervention/treatment	Phase
Hepatocellular Carcinoma	Drug: Sorafenib; Drug: HAIC of FOLFOX; Drug: HAIC of OXA	Phase 2

Detailed Description:

Sorafenib is the most widely used palliative treatment for advanced hepatocellular carcinoma (HCC) patients . Our previous prospective study revealed that sorafenib combined with hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin plus fluorouracil/leucovorin confer a survival benefit to advanced HCC . However, HAIC of fluorouracil is not such for advanced HCC. Whether HAIC of oxaliplatin is as effective as HAIC of oxaliplatin plus fluorouracil/leucovorin is controversial. Thus, the investigators carried out this prospective randomized control study to find out it.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 150 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Sorafenib Plus Hepatic Artery Infusion Chemotherapy of Oxaliplatin, Fluorouracil/Leucovorin Versus Sorafenib Plus Hepatic Artery Infusion Chemotherapy of Oxaliplatin for Advanced Hepatocellular Carcinoma
• Actual Study Start Date: August 4, 2018
• Estimated Primary Completion Date: September 1, 2019
• Estimated Study Completion Date: September 1, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sorafenib plus HAIC of OXA; Sorafenib combined with Hepatic arterial infusion chemotherapy with Oxaliplatin	Drug: Sorafenib; Oral Sorafenib, 400mg, Bid; Drug: HAIC of OXA; administration of Oxaliplatin via the tumor feeding arteries; Other Name: Oxaliplatin
Active Comparator: Sorafenib plus HAIC of FOLFOX; Sorafenib combined with Hepatic arterial infusion chemotherapy with Oxaliplatin, Fluorouracil and Leucovorin	Drug: Sorafenib; Oral Sorafenib, 400mg, Bid; Drug: HAIC of FOLFOX; administration of Oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries; Other Name: Oxaliplatin , fluorouracil, and leucovorin

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: 12 months ]
   PFS was defined as the time from the date of randomization to the date of first documentation of disease progression based on modified Response Evaluation Criteria in Solid Tumors (mRECIST), or date of death, whichever occurred first.

Secondary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: 12 months ]
   OS was defined as the duration from the date of randomization until the date of death from any cause. Participants who were lost to follow-up were censored at the last date the participant was known to be alive, and participants who remained alive were censored at the time of data cutoff.
2. Objective Response Rate (ORR) [ Time Frame: 12 months ]
   ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on mRECIST. CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference to the baseline sum of the diameters of target lesions.
3. Adverse Events [ Time Frame: 30 days ]
   Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.03

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL)
• Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria.
• Barcelona clinic liver cancer-stage C
• Eastern Cooperative Oncology Group performance status of 0 to 2
• with no previous treatment
• No Cirrhosis or cirrhotic status of Child-Pugh class A only
• Not amendable to surgical resection ,local ablative therapy and any other cured treatment.
• The following laboratory parameters:

Platelet count ≥ 75,000/μL Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 30mmol/L Serum albumin ≥ 30 g/L ASL and AST ≤ 5 x upper limit of normal Serum creatinine ≤ 1.5 x upper limit of normal INR ≤ 1.5 or PT/APTT within normal limits Absolute neutrophil count (ANC) >1,500/mm3

• Ability to understand the protocol and to agree to and sign a written informed consent document

Exclusion Criteria:

• Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy
• Known history of HIV
• History of organ allograft
• Known or suspected allergy to the investigational agents or any agent given in association with this trial.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
• Evidence of bleeding diathesis.
• Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
• Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug
• Serious non-healing wound, ulcer, or bone fracture
• Known central nervous system tumors including metastatic brain disease

Contacts and Locations

Locations

China, Guangdong

Cancer Center Sun Yat-sen University; Recruiting

Guangzhou, Guangdong, China, 510060

Contact: Ming Shi 86-2087343154 ext 86-2087343154 shiming@mail.sysu.edu.cn

Contact: Ping Rong, Guo 86-2087342266 ext 86-2087342266 guorongp@mail.sysu.edu.cn

Principal Investigator: Ming Shi

Guangzhou Twelfth People 's Hospita; Recruiting

Guangzhou, Guangdong, China, 510620

Contact: Yuanmin Zhou, MD 15521278919 13430288977@139.com

Principal Investigator: Jinghua Chen, MD

Kaiping Central Hospital; Recruiting

Kaiping, Guangdong, China, 529300

Contact: WanQiang Fang, MD 13717287622 fangwanqiang1970@sina.com

Sponsors and Collaborators

Sun Yat-sen University

Kaiping Central Hospital

Guangzhou No.12 People's Hospital

More Information

• Responsible Party: Shi Ming, Clinical Professor, Sun Yat-sen University
• ClinicalTrials.gov Identifier: NCT03812770
• Other Study ID Numbers: HCC-OXA
• First Posted: January 23, 2019
• Last Update Posted: April 17, 2019
• Last Verified: January 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shi Ming, Sun Yat-sen University:

Hepatocellular Carcinoma; Sorafenib; Hepatic artery infusion chemotherapy; Oxaliplatin, 5-Fluorouracil and Leucovorin; Oxaliplatin

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Leucovorin; Fluorouracil; Oxaliplatin; Sorafenib; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antidotes; Protective Agents; Vitamin B Complex; Vitamins; Micronutrients; Protein Kinase Inhibitors; Enzyme Inhibitors