SOON: A RCT of Oral S-1 in Combination With Sequential HAIC of Oxaliplatin After TACE in Patients With Advanced HCC

Sponsor

Zhu Xu (Other)

Overall Status

Unknown status

CT.gov ID

NCT01997957

Collaborator

(none)

110

Enrollment

Location

Arms

Study Details

Study Description

Brief Summary

Hepatocellular carcinoma (HCC) is one of the most commonly malignant tumors around the world and causes death of about 600000~1000000 people each year. Since 1990s, hepatic carcinoma has become the second carcinoma killer in China. Surgical resection or liver transplantation is the only method possibly able to cure hepatic carcinoma. However, due to multiple tumors or poor hepatic function reserve in cirrhosis, surgical treatment is suitable for only a small portion of patients (11.9%-30.1%). Therefore, in clinical practice, transarterial chemoembolization (TACE) or transarterial embolization (TAE) is a preferential and standard treatment of unresectable advanced hepatic carcinoma and has notable advantages in controlling local tumors of the liver. Hepatic arterial infusion of oxaliplatin after TACE can significantly increase the local doses of chemotherapeutic agents in the liver, kill micrometastases and residual foci after embolization and demonstrate outstanding efficacy for treating concomitant portal and hepatic vein tumor thrombi. S-1 is a chemotherapeutic agent with convenient use and definite efficacy and, when used concomitantly with TACE, theoretically can not only effectively control intrahepatic foci but also prevent and control extrahepatic metastatic foci. However, this hasn't been verified in clinical application. This study is intended to investigate efficacy and safety of the combination treatment so as to provide a more effective and safety way for treating patients with advanced hepatic carcinoma (Barcelona stage-C patients with concomitant portal vein tumor thrombi or extrahepatic metastasis).

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: S-1	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

110 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Controled Trial of Oral S-1 in Combination With Sequential Hepatic Arterial Infusion of Oxaliplatin After Transarterial Chemoembolization in Patients With Advanced Hepatocellular Carcinoma

Study Start Date :

Oct 1, 2013

Anticipated Primary Completion Date :

Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TACE+HAIC-OXA+S-1	Drug: S-1 Begin oral administration of S-1 from the 2nd day after TACE therapy plus arterial indwelling catheter chemotherapy (Oxaliplatin)
No Intervention: TACE+HAIC-OXA

Arm

Intervention/Treatment

Experimental: TACE+HAIC-OXA+S-1

Drug: S-1

Begin oral administration of S-1 from the 2nd day after TACE therapy plus arterial indwelling catheter chemotherapy (Oxaliplatin)

No Intervention: TACE+HAIC-OXA

Outcome Measures

Primary Outcome Measures

Time to progression(TTP) [Up to 2 years]
Time to clinically definite disease progression

Secondary Outcome Measures

Overall survival(OS) [Up to 2 years]
Response rate (RR) [Up to 2 years]
The percentage of patients showing partial or complete response to the given treatment
Disease Control Rate (DCR) [Up to 2 years]
The percentage of patients showing partial or complete response or stable disease to the given treatment
Number of Participants with Serious and Non-Serious Adverse Events [Up to 3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signing the informed consent form;
Diagnosed with HCC

Patients with hepatic cirrhosis must comply with AASLD (American Association for the Study of Liver Diseases) diagnostic criteria:

Typical radiological examination (ultrasonography, CT or MRI) manifestations: dynamic enhanced examination shows arterial-phase rapid heterogeneous enhancement and reduced venous-phase or delayed-phase rapid enhancement of space occupation in liver;

If the diameter of space occupation in liver is ≥2cm, the diagnosis can be established if any of radiological examinations shows the above HCC characteristics;
If the diameter of space occupation in liver is 1-2cm, the diagnosis can be established only when two radiological examinations show the above HCC characteristics;
If the diameter of space occupation in liver is≤1cm, histopathological examination is needed for establishing the diagnosis.

Histopathological examination is needed for establishing the diagnosis for patients without hepatic cirrhosis.

Stage Barcelona C
Grade A or B Child-Pugh score
ECOG PS score is 0-1
At least one measurable focus in liver according to (M) RECIST 1.0 criteria
Male or female, age>18
Can orally take drugs
Anticipated survival≥12 weeks
Pregnancy test of women at child-bearing ages must be negative within the 7 days before treatment
Male or female patients included must take effective contraceptive measures during the study period and within 4 weeks after completion of the study
Within the 7 days before inclusion, bone marrow, liver and kidney functions must satisfy the following requirements:
Hemoglobin≥ 90 g/L
Absolute neutrophil count (ANC) >1,500/mm3
Platelet count≥ 80x109/L
Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5 times the upper normal limit (UNL)
Total bilirubin < 3UNL
Alkaline phosphatase < 4UNL
Serum creatinine < 1.5 UNL
Amylase and lipase < 2 UNL
INR<2.3 or PPT< 1.5 UNL (Patients who are accepting Warfarin or heparin anticoagulant therapy may be included if no evidence is available proving the above indicators are abnormal, but intense monitoring must be exercised. Tests shall be carried out at least once per week until stable INR.)

Exclusion Criteria:

Early or middle-stage primary HCC
Any contraindication of TACE therapy
Known hepatofugal blood flow
Known portal-systemic shunt
Abnormal coagulation test (PLT<6000/mm3, thrombogen activity<50%)
Renal failure or renal insufficiency necessitating dialysis
Serious atherosclerosis
Foci having undergone local treatment (e.g. resection, RFA, PEI or argon-helium cryoablation) cannot be used as the target foci
Local therapy or systemic chemotherapy within 4 weeks before inclusion or during the study period
Acute toxic reaction of CTC grade AE2 or above in any local treatment before inclusion
History of heart diseases:
Congestive heart failure of NYHA grade 2 above
Symptomatic coronary artery disease
Arrhythmia needing treatment with β blockers or drugs other than digoxin
uncontrollable hypertension
HIV infection or AIDS-related diseases
Serious active infections other than hepatitis B and hepatitis C (NCI-CTCAE 4.0 grade 2 above)
Gastrointestinal hemorrhage event within 4 weeks before inclusion
Thrombogenesis or embolism event within 6 months before inclusion, e.g. cerebral vascular accidents (including TIA), deep venous thrombogenesis or pulmonary embolisms
Past or present history of concomitant tumors completely different from HCC in primary lesions or histology, excluding head and neck carcinoma in situ, cured basal cell carcinoma, superficial bladder carcinoma (Ta, Tis, T1) and tumors having been cured 3 years before inclusion
Drug abuse, or psychological or mental diseases that may interfere with the study compliance
Known or suspected allergy to the study drug or concomitant medications
Contraindications of S-1
Pregnancy or lactation
Any disease that may affect evaluation of the study drug
Any instability or condition that may impair the patient's safety and compliance in the study
Gastrointestinal diseases affecting absorption or pharmacokinetics
Conditions restricting the patient from taking drugs orally, including serious upper gastrointestinal obstruction
Having accepted TACE before inclusion
Having taken S-1 before inclusion
Having accepted liver radiotherapy before inclusion or during the study period
Having accepted biological regulators, e.g. G-CSF, within the 3 weeks before inclusion
Having accepted autologous bone marrow transplantation or stem cell transplantation within 1 year before inclusion
History of homoplastic transplantation
Any drug that may affect absorption or pharmacokinetics of the study drug
Poor compliance considered by the investigator