Phase Ⅱ Study of HAIC of FOLFOX vs. Sorafenib in HCC Refractory to TACE

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03722498

Collaborator

Guangzhou No.12 People's Hospital (Other), Kaiping Central Hospital (Other)

100

Enrollment

Locations

Arms

33.7

Anticipated Duration (Months)

33.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate safety and efficacy of combined hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, 5-fluorouracil and leucovorin and sorafenib in hepatocellular carcinoma (HCC) refractory to transarterial chemoembolization(TACE)

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: HAIC of FOLFOX Drug: Sorafenib	Phase 2

Detailed Description

In most current guidelines, sorafenib is considered as the second-line treatment for patients with transarterial chemoembolization(TACE) failure or refractoriness.However,the median overall survival of those treated with sorafenib monotherapy was 16.4 to 24.7 months.

Whether combining sorafenib with hepatic arterial infusion chemotherapy(HAIC) of oxaliplatin,5-fluorouracil and leucovorin is safe, well tolerated, and efficacious remains unknown, with no prospective clinical data currently available.The investigators therefore conducted a prospective and randomized phase II trial to compare the safety and efficacy of HAIC with sorafenib in patients refractory to TACE

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomized Phase Ⅱ Study of Second-line Treatment Comparing Hepatic Arterial Infusion Chemotherapy of Oxaliplatin, 5-fluorouracil and Leucovorin With Sorafenib in Hepatocellular Carcinoma Refractory to Transarterial Chemoembolization

Actual Study Start Date :

Jun 1, 2018

Anticipated Primary Completion Date :

Mar 22, 2021

Anticipated Study Completion Date :

Mar 22, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HAIC of FOLFOX Hepatic arterial infusion chemotherapy with oxaliplatin, leucovorin, and 5-fluorouracil	Drug: HAIC of FOLFOX administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries Other Names: Oxaliplatin , fluorouracil, and leucovorin
Active Comparator: Sorafenib Sorafenib 400 mg orally twice a day	Drug: Sorafenib administration of Sorafenib

Arm

Intervention/Treatment

Experimental: HAIC of FOLFOX

Hepatic arterial infusion chemotherapy with oxaliplatin, leucovorin, and 5-fluorouracil

Drug: HAIC of FOLFOX

administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries

Other Names:

Oxaliplatin , fluorouracil, and leucovorin

Active Comparator: Sorafenib

Sorafenib 400 mg orally twice a day

Drug: Sorafenib

administration of Sorafenib

Outcome Measures

Primary Outcome Measures

Progression-free survival [12 months]
The period from the date of the start of HAIC or sorafenib until the date of the confirmation of tumor progression or death

Secondary Outcome Measures

Overall survival [12 months]
The period from the date of the start of HAIC or sorafenib until the date of the confirmation of tumor progression or death
Adverse Events [30 Days after HAIC and TACE]
Postoperative adverse events were graded based on CTCAE v4.03
Objective response rate [12 months]
Best response based on mRECIST

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

TACE failure or refractoriness based on the Liver Cancer Study Group of Japan (LCSGJ) criteria, including appearance of vascular invasion or two or more consecutive insufficient responses of the intrahepatic lesion;
Except for TACE, patients have received no previous anti-tumor treatment;
The diagnosis of HCC was based on histological results;
Patients must have at least one tumor lesion that can be accurately measured;
Not amendable to surgical resection ,local ablative therapy and any other cured treatment;
No Cirrhosis or cirrhotic status of Child-Pugh class A only;
No liver protection therapy in 2 weeks before enrolled, and meet the following laboratory parameters:(a) Platelet count ≥ 75,000/μL; (b)Hemoglobin ≥ 8.5 g/dL;(c) Total bilirubin ≤ 30mmol/L;(d) Serum albumin ≥ 32 g/L;(e) ASL and AST ≤ 5 x upper limit of normal;(f) Serum creatinine ≤ 1.5 x upper limit of normal;(g) INR > 2.3 or PT/APTT within normal limits; (h) 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;
Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Guangzhou Twelfth People 's Hospital	Guangzhou	Guangdong	China	510620
2	Ming Shi	Guangzhou	Guangdong	China
3	Kaiping Central Hospital	Kaiping	Guangdong	China	529300