| Titre |
Randomized Phase III Study of Sorafenib Versus Stereotactic Body Radiation Therapy Followed by Sorafenib in Hepatocellular Carcinoma
|
| Protocole ID |
RTOG 1112 |
| ClinicalTrials.gov ID |
NCT01730937 |
| Type(s) de cancer |
Foie |
| Phase |
Phase III |
| Type étude |
Traitement |
| Institution |
CENTRE UNIVERSITAIRE DE SANTE MCGILL
 SITE GLEN
1001 boul. Décarie , Montréal, QC, H4A 3J1
|
| Ville |
Montréal |
| Investigateur(trice) principal(e) |
Dr Neil Kopek
|
| Coordonnateur(trice) |
Tatiana Carvalho
514-934-1934 poste 43698
|
| Statut |
![]() Fermé |
| Date d'activation |
16-07-2018 |
| Critètes d'éligibilité |
-
Patients must have a diagnosis of HCC by at least one criterion listed below within 360 days prior to study entry:
- Pathologically (histologically or cytologically) proven diagnosis of HCC,(biopsies are recommended, and are to be submitted for research evaluation if patients consent)
- At least one solid liver lesion or vascular tumor thrombosis (involving portal vein, inferior vena cava [IVC] and/or hepatic vein) > 1 cm with arterial enhancement and delayed washout on multi-phasic computerized tomography (CT) or magnetic resonance imaging (MRI) in the setting of cirrhosis or chronic hepatitis B or C without cirrhosis.
- For patients whose CURRENT disease is vascular only: enhancing vascular thrombosis (involving portal vein, IVC and/or hepatic vein) demonstrating early arterial enhancement and delayed washout on multi-phasic CT or MRI in a patient with known HCC (diagnosed previously) using the above criteria.
- Measureable hepatic disease and/or presence of vascular tumor thrombosis (involving portal vein, IVC and/or hepatic vein) which may not be measureable as per Response Evaluation Criteria in Solid Tumors (RECIST) on liver CT or MRI, within 28 days of registration
-
Appropriate for protocol entry based upon the following minimum diagnostic workup:
- History/physical examination including examination for encephalopathy, ascites, weight, height, and blood pressure within 14 days prior to study entry
- Assessment by radiation oncologist and medical oncologist or hepatologist who specializes in treatment of HCC within 28 days prior to study entry
- Pre-randomization Scan (REQUIRED for All Patients): CT scan chest/abdomen/pelvis with multiphasic liver CT scan within 28 days prior to study entry; if CT contrast is contraindicated, CT chest without contrast and MRI of abdomen and pelvis is permitted
- Zubrod performance status 0-2 within 28 days prior to study entry
- Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
- Platelets >= 70,000 cells/mm^3
- Hemoglobin >= 8.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
- Total bilirubin < 2 mg/dL
- Prothrombin time/international normalized ratio (INR) < 1.7
- Albumin >= 28 g/L
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 6 times upper limit of normal (ULN)
- Serum creatinine =< 1.5 x ULN or creatinine clearance >= 60 mL/min
- Barcelona Clinic Liver Cancer (BCLC) stage: intermediate (B) or advanced (C) within 14 days prior to study entry
- Child-Pugh score A within 14 days prior to study entry
- Women of childbearing potential and male participants must agree to practice adequate contraception while on study and for at least 6 months following the last dose of radiation therapy (RT) and for at least 28 days following the last dose of sorafenib (whichever is later)
- Unsuitable for resection or transplant or radiofrequency ablation (RFA)
-
Unsuitable for or refractory to transarterial hepatic chemo-embolization (TACE) or drug eluting beads (DEB) for any of the following reasons, as described by Raoul et al (2011):
- Technical contraindications: arteriovenous fistula, including transjugular intrahepatic portosystemic shunt (TIPS), surgical portosystemic shunt, spontaneous portosystemic shunt or hepatofugal portal vein flow
- Severe reduction in portal vein flow: due to tumor portal vein, IVC or atrial invasion or bland portal vein occlusion
- Medical contraindications including congestive heart failure, angina, severe peripheral vascular disease
- Presence of extrahepatic disease
- No response post TACE (or DEB) x 2 or progressive HCC despite TACE; prior TACE or DEB is allowed but must be > 28 days from study entry
- Serious toxicity following prior TACE (or DEB); prior TACE or DEB must be > 28 days from study entry
- Other medical comorbidities making TACE (or DEB) unsafe and/or risky (e.g. combination of relative contraindications including age > 80 years, tumor > 10 cm, > 50% replacement of the liver by HCC, extensive multinodular bilobar HCC, biliary drainage)
- Patients treated with prior surgery are eligible for this study if they otherwise meet eligibility criteria
- Patient must be able to provide study-specific informed consent prior to study entry
|
| Critètes d'exclusion |
- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years (note that carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
- Prior sorafenib use; note that prior chemotherapy for HCC or a different cancer is allowable
- Prior radiotherapy to the region of the liver that would result in overlap of radiation therapy fields
- Prior selective internal radiotherapy/hepatic arterial yttrium therapy, at any time
-
Severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months before registration
- Transmural myocardial infarction within the last 6 months prior to study entry
- Unstable ventricular arrhythmia within the last 6 months prior to study entry
- Acute bacterial or fungal infection requiring intravenous antibiotics within 28 days prior to study entry
- Hepatic insufficiency resulting in clinical jaundice, encephalopathy and/or variceal bleed within 60 days prior to study entry
- Bleeding within 60 days prior to study entry due to any cause, requiring transfusion
- Thrombolytic therapy within 28 days prior to study entry. Subcutaneous heparin is permitted.
- Known bleeding or clotting disorder
- Uncontrolled psychotic disorder
- Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
- Any one hepatocellular carcinoma > 15 cm
- Total maximal sum of hepatocellular carcinomas or a single conglomerate HCC > 20 cm
- More than 5 discrete intrahepatic parenchymal foci of HCC
- Direct tumor extension into the stomach, duodenum, small bowel or large bowel
- Measureable common or main branch biliary duct involvement with HCC
- Extrahepatic metastases or malignant nodes (that enhance with typical features of HCC) > 2.0 cm, in sum of maximal diameters (e.g. presence of one 2.4 cm metastatic lymph node or two 1.2 cm lung lesions); note that benign non-enhancing periportal lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if the sum of enlarged nodes is > 2.0 cm
- Use of regular phenytoin, carbamazepine, hypericum perforatum (also known as St. John's wort) or rifampin
- Use of combination anti-retroviral therapy for human immunodeficiency virus (HIV), as these agents may modulate cytochrome P450 isozymes
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Groupe d'étude en oncologie du Québec