Clinical trial NCT00990860: Study in Asia of the Combination of TACE With Sorafenib in HCC Patients
Official title: START (Study in Asia of the Combination of Transcatheter Arterial Chemoembolization (TACE) With Sorafenib in Hepatocellular Carcinoma (HCC) Patients) Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: Combination of TACE With Sorafenib
Lead sponsor: Taipei Veterans General Hospital, Taiwan
Sponsor class: OTHER_GOV
First posted: 2009-10-07
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: TACE possibly plays a significant role in contributing to a subgroup of surviving residual tumor tissue which is characterized by more aggressive biology. This explains the strong scientific rationale for exploring the role of anti-angiogenic therapy such as sorafenib to remedy and strengthen the therapeutic efficacy of TACE to combat liver cancers. Sorafenib plays a prominent auxiliary role by further suppressing the tumor growth and prolonging the time to recurrence and progression. Performing TACE under sorafenib administration may have synergic effect on hepatic tumoral lesions.


Eligibility criteria: Inclusion Criteria:

* Age ≧ 18
* life expectancy \> 12 weeks
* Histologically diagnosed HCC, OR clinically diagnosed HCC for patients with difficulty in obtaining histological diagnosis. A clinically diagnosed HCC should fulfill ALL the criteria below

  * Chronic hepatitis B or C and/or evidence of liver cirrhosis.
  * Presence of hepatic tumour(s) with image findings compatible with HCC, and no evidence of other gastrointestinal tumours
  * A persistent elevation of serum AFP \>= 400 ng/ml without any evidence of an existing α-fetoprotein-secreting germ cell tumour
* Child-Pugh score ≦ 7
* BCLC B
* The patient must have a solitary hepatic tumour greater than 3 cm in diameter or multifocal disease as evidenced by CT or MRI scanning.
* The target lesion must not have been previously treated with local therapy
* The patient must not be a candidate for surgical resection or ablation of the tumour. Size of largest tumor ≦10cm in largest dimension
* Patients who have received previous local therapy treatments (RFA, PEI, cryoablation, surgery, resection) to non-target lesions are eligible
* Local therapy must have been completed at least 4 weeks prior to baseline scan.
* ECOG performance status 0 or 1
* Hb ≧ 9g/dL,
* Absolute neutrophil count \> 1000/mm3
* Platelet count ≧ 60x109/L
* Adequate clotting function: INR \< 1.5
* Hepatic: AST or ALT \< 5 X ULN
* Renal: serum creatinine \< 1.5 x ULN
* Bilirubin ≦ 3mg/dL
* The patient must give written, informed consent

Exclusion Criteria:

* Tumor factors

  * Presence of extrahepatic metastasis
  * Predominantly infiltrative lesion
  * Diffuse tumor morphology with extensive lesions involving both lobes.
* Vascular complications

  * Hepatic artery thrombosis, or
  * Partial or complete thrombosis of the main portal vein, or
  * Tumor invasion of portal branch of contralateral lobe, or
  * Hepatic vein tumor thrombus, or
  * Significant arterioportal shunt not amenable to shunt blockage
* Liver function

  * Advanced liver disease: ascites, hepatic encephalopathy
  * Patients with clinically significant gastrointestinal bleeding within the 30 days prior to study entry.
* Others

  * Pregnant or lactating women.
  * Active sepsis or bleeding.
  * Hypersensitivity to intravenous contrast agents.
  * The patient has received prior treatment for HCC target lesion.
  * History of cardiac disease

    * Congestive heart failure \> NYHA class 2; active coronary artery disease
    * Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
  * Hypertension defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg despite optimal medical management.
  * Therapeutic anticoagulation with coumarin, heparins, or heparinoids.
  * Serious non-healing wounds (including wounds healing by secondary intention), acute or non-healing ulcers, or bone fractures within 3 months.
  * Impairment of swallowing that would preclude administration of sorafenib.
  * The patient is, in the opinion of the investigator, unable and / or unwilling to comply with treatment and study instructions.
  * Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis \& T1). Any cancer curatively treated \> 3 years prior to entry is permitted
  * Any active clinically serious infections (\> grade 2 NCI-CTCAE ver 3.0)
  * HIV infection or AIDS-related illness or serious acute or chronic illness (based on medical history)

Primary outcomes:
measure: Safety and tolerability (such as adverse events and laboratory changes (haematology, clinical chemistry))
timeFrame: 2 years
Secondary outcomes:
measure: Time to Progression
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
measure: Progression Free Survival
timeFrame: 2 years
measure: No. of TACE cycles
timeFrame: 2 years
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: E-Da hospital
city: Kaoshiung
country: Taiwan
facility: Veterans General Hospital- Kaochiung
city: Taichung
country: Taiwan
facility: Veterans General Hospital- Taichung
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Taipei
country: Taiwan
facility: Tri- Service General Hospital
city: Taipei
country: Taiwan
facility: Veterans General Hospital- Taipei
city: TaoYuan Hsien
country: Taiwan
facility: Chang-Gung Memorial Hospital- LinKou
Study officials:
affiliation: VGH-TPE
name: Yee Chao
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chao Y, Chung YH, Han G, Yoon JH, Yang J, Wang J, Shao GL, Kim BI, Lee TY. The combination of transcatheter arterial chemoembolization and sorafenib is well tolerated and effective in Asian patients with hepatocellular carcinoma: final results of the START trial. Int J Cancer. 2015 Mar 15;136(6):1458-67. doi: 10.1002/ijc.29126. Epub 2014 Sep 16.