YES-P Clinical
Trial Information

Protocol TS-104 / NCT01887717

An international Phase III prospective randomized clinical trial evaluating yttrium-90 trans-arterial radioembolization (TheraSphere®) versus the standard of care (sorafenib) for the treatment of advanced hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT)

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An open-label, prospective, multicenter, randomized, Phase III clinical trial evaluating yttrium-90 transarterial radioembolization (TheraSphere®) versus the standard of care (sorafenib) for the treatment of advanced hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT).29,30

RANDOMIZE TREATMENT GROUP
TheraSphere®

CONTROL GROUP
Standard-of-care therapy: sorafenib

ENDPOINTS
Primary: Overall survival
Secondary: Time to progression, time to worsening portal vein thrombosis, response rate, time to symptomatic progression, quality of life (FACT-hep), safety

Objective
To assess efficacy and safety of TheraSphere® in comparison to sorafenib therapy in the treatment of patients with PVT associated with unresectable HCC.

Primary Endpoint
  • Overall survival from time of randomization

Secondary Endpoint
  • Time to progression (from time of randomization by RECIST v1.1, mRECIST, and EASL criteria)
  • Time to worsening of PVT (from time of randomization to time of any change in classification of PVT type by at least one sub-type)
  • Time to symptomatic progression (from time of randomization to assessment of ECOG performance status ≥2 with or without tumor progression based on imaging; deterioration in performance status is to be confirmed at one subsequent evaluation 8 weeks later)
  • Tumor response (by RECIST v1.1, mRECIST, and EASL criteria)
  • Patient reported outcome (PRO) (FACT-hep)
  • Adverse events (CTCAE v4.0)

Inclusion Criteria
  • Patients 18 years of age or older, regardless of race or gender
  • Advanced-stage HCC confirmed by histology (mandatory in noncirrhotic patients) or noninvasive criteria (EASL/AASLD) with branch portal vein thrombosis
    • Either naive or recurrent HCC after curative treatment (minimum 3 months from curative treatment - minor resection or local ablation) is acceptable.
    • Branch PVT classified as Type I, Type II or Type IIIa
    • Unilobar disease
    • Tumor volume ≤70% of liver volume (determined by visual estimation)
  • Child-Pugh A
  • At least one unidimensional HCC target lesion assessable according to the RECIST v1.1 criteria by CT-scan or MRI
  • ECOG status 0-1
  • PLT ≥50 x103/μL
  • WBC ≥1.5 x103/μL
  • AST/ALT ≤5 times the upper limit of normal (U/L)
  • Creatinine ≤2.0 mg/dL
  • In case of patients progressing from an intermediate to an advanced stage because of occurrence of PVT, enrollment is allowed if previous conventional or drug eluting TACE was performed at least 3 months prior to screening phase
  • Negative serum pregnancy test in females of child-bearing potential
  • Life expectancy of greater than 3 months
  • Signed informed consent form

Exclusion Criteria
  • Confirmed extrahepatic metastases. Patients with indeterminate hepatic hilar lymph nodes up to 2.5 cm in greatest dimension, or with indeterminate lung nodules (single lesion between 1-1.5 cm, or multiple smaller lesions with a total diameter ≤2 cm) may be included if metastatic disease is deemed unlikely
  • Known contraindications to standard-of-care sorafenib including allergic reaction, pill-swallowing difficulty, uncontrolled hypertension or history of cardiac disease (according to sorafenib package insert and country-specific policies, may include evidence of severe or uncontrolled systemic diseases, cardiac arrhythmias (requiring anti-arrhythmic therapy or pace maker), congestive cardiac failure > New York Heart Association class 2, myocardial infarction within 6 months, prolonged QT/QTc >450ms), or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial, significant GI bleeding within 30 days, renal failure requiring dialysis
  • Evidence of hepatic vein invasion or caval thrombosis
  • Evidence of pulmonary insufficiency or clinically evident chronic obstructive pulmonary disease
  • Eligible for curative treatment after multidisciplinary assessment, including liver transplant, surgery, or ablation
  • Previous treatment with sorafenib for more than 4 weeks during the previous 2 months; prior sorafenib-related toxicity at any dose and/or duration defined as documented sorafenib-related grade 3 or 4 adverse events that led to sorafenib discontinuation
  • Initiation of any other antitumor therapy including chemotherapy, radioembolization (maximum lung shunt of 20% for prior radioembolization) or investigational drug treatment within 30 days before the beginning of the study
  • Inclusion on a liver transplantation list
  • History of organ allograft
  • Contraindication to angiography or selective visceral catheterization
  • History of severe allergy or intolerance to contrast agents, narcotics, sedatives or atropine that cannot be managed medically
  • Prior external beam radiation therapy to the liver
  • Evidence of continuing adverse effect of prior therapy
  • Active GI bleeding and any bleeding diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agents (e.g., closure device)
  • Evidence of any disease or condition that would place the patient at undue risk and preclude safe use of microsphere (TheraSphere®) treatment
  • Patients who are breastfeeding
  • Participation in concurrent interventional clinical trials