STOP-HCC Clinical
Trial Information

Protocol TS-103 / NCT01556490

An international Phase III clinical trial evaluating yttrium-90 trans-arterial radioembolization (TheraSphere®) in the treatment of patients with unresectable hepatocellular carcinoma (HCC)

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An open-label, prospective, multicenter, randomized, Phase III clinical trial evaluating yttrium-90 transarterial radioembolization (TheraSphere®) in the treatment of patients with unresectable hepatocellular carcinoma (HCC).27,28

RANDOMIZE TREATMENT GROUP
TheraSphere® prior to initiation of standard-of-care therapy: sorafenib

CONTROL GROUP
Standard-of-care therapy: sorafenib

ENDPOINTS
Primary: Overall survival
Secondary: Time to progression, tumor response, time to symptomatic progression, quality of life (FACT-hep), time to untreatable progression, safety

Objective
To evaluate the efficacy and safety of TheraSphere® in patients with unresectable HCC in whom treatment with sorafenib is planned.

Primary Endpoint
  • Overall survival from time of randomization

Secondary Endpoint
  • Time to progression (from time of randomization based on investigator assessment according RECIST criteria v1.1)
  • Time to untreatable progression (from time of randomization based on one or more of the following: investigator assessment according to RECIST criteria v1.1, contraindication to protocol treatments based on package insert or patient performance status)
  • Time to symptomatic progression (from time of randomization to ECOG performance status >1 with or without tumor progression based on investigator assessment according to RECIST criteria v1.1)
  • Tumor response (according to RECIST v1.1 criteria based on investigator assessment)
  • Quality of life (Functional Assessment of Cancer Therapy - Hepatobiliary Questionnaire FACT-hep)
  • Adverse events (CTCAE v4.0)

Inclusion Criteria
  • Signed informed consent prior to any study-related evaluation.
  • Patients 18 years of age or older, male or female
  • Unresectable HCC confirmed by histology or by noninvasive AASLD criteria
  • Measurable disease defined as at least one unidimensional measurable lesion by CT or MRI (according to RECIST v1.1)
  • Child-Pugh score ≤7 points
  • ECOG status 0-1
  • Life expectancy of 12 weeks or more
  • Eligible to receive standard-of-care sorafenib
  • Platelet count >50 x 109/L or >50% prothrombin activity
  • Hemoglobin ≥8.5 g/dL
  • Bilirubin ≤2 mg/dL
  • ALT and AST must be <5X upper limit of normal
  • Amylase or lipase must be ≤1.5X upper limit of normal
  • Serum creatinine must be ≤1.5X upper limit of normal
  • INR must be <2.0
  • Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to randomization

Exclusion Criteria
  • Eligible for curative treatment (ablation or transplantation)
  • Main portal vein thrombosis (branch portal vein thrombosis is permissible)
  • Eligible for transarterial chemoembolization (TACE), in the judgment of the investigator
  • History of previous or concurrent cancer other than HCC unless treated curatively 5 or more years prior to entry
  • History of organ allograft
  • Confirmed presence of extrahepatic disease except lung nodules and mesenteric or portal lymph nodes ≤2.0 cm each
  • At risk of hepatic or renal failure
  • Tumor replacement >70% of total liver volume based on visual estimation by the investigator OR tumor replacement >50% of total liver volume in the presence of albumin <3 mg/dL
  • History of severe allergy or intolerance to contrast agents, narcotics, sedatives or atropine that cannot be managed medically
  • Contraindications to angiography and selective visceral catheterization
  • Contraindications to sorafenib including allergic reaction, pill-swallowing difficulty, uncontrolled hypertension or history of cardiac disease, significant GI bleed within 30 days, metastatic brain disease, renal failure requiring dialysis
  • Taking any of the following: Rifampicin, St. John's Wort, phenytoin, carbamazepine, phenobarbital, and dexamethasone
  • Taking any other systemic anticancer agent (docetaxel, doxorubicin, irinotecan)
  • Taking any substrate agents for CYP2B6 (buproprion, cyclophosphamide, efavirenz, ifosfamide, methadone, paclitaxel, amodiaquine, repaglinide)
  • Taking any UGT 1A1 and UGT 1A9 substrates (e.g., irinotecan)
  • Taking P-Gp substrates (e.g., Digoxin)
  • Any prior liver resection must have taken place >6 months prior to randomization
  • Prior external beam radiation treatment to the liver or abdomen
  • Prior yttrium-90 microsphere treatment to the liver
  • Prior treatment with transarterial chemoembolization (TACE) or bland embolization must have occurred >6 months prior to randomization and must have been applied to a treatment field and/or lobe that is not to be treated under this protocol or, for lobes previously treated with TACE feeding vessels must be assessed for adequate blood supplies
  • Anticancer therapy or any treatment with an investigational agent within 30 days prior to randomization
  • Adverse effects due to prior therapy that are unresolved at randomization
  • Prior systemic therapy for the treatment of HCC, including sorafenib given for more than 4 weeks during the 2 previous months; no related toxicites
  • History of pulmonary compromise, such as chronic obstructive pulmonary disease
  • Intervention for, or compromise of, the Ampulla of Vater
  • Clinically evident ascites (trace ascites on imaging is acceptable)
  • Pregnant or breastfeeding
  • Any disease or condition that would preclude the safe use of TheraSphere®, including concurrent dialysis treatment, or unresolved serious infections including patients who are known HIV-positive