In- and exclusion criteria

Transcription

1 In- and exclusion criteria Kerstin Schütte Department of Gastroenterology, Hepatology and Infectious Diseases University of Magdeburg

2 Overview: Study population

3 Inclusion criteria I - General criteria Male or female Age: years diagnosis of hepatocellular carcinoma Stage BCLC A, B or C Written informed consent (voluntarily given) Patient willing to comply with all study procedures

4 Criteria for primary diagnosis of HCC: options A Cyto-histologically proven B radiological criteria: focal lesion > 1cm in size arterial hypervascularisation in 2 coincident imaging techniques (CT, MRI, US)

5 C combined criteria: Criteria for primary diagnosis of HCC: options focal lesion 1-2 cm in size arterial hypervascularisation in one imaging technique AFP level > 400 ng/ml D combined criteria: focal lesion > 2 cm in size arterial hypervascularisation in one imaging technique AFP level > 200 ng/ml

6 BCLC-Staging System

7 Child-Pugh classification Performance Status Very early stage (0) Tumor status 1 HCC < 2 cm Carcinom a in situ BCLC-Staging Early stage (A) System Intermediat e stage (B) Advanced stage (C) A A-B A-B A-B C HCC or 3 nodules < 3 cm Multinodular Portal invasion or N1/M1 Terminal stage (D) Terminal stage

8 Inclusion criteria II General criteria Child-Pugh A or B up to 7 points

9 measure Child-Pugh Classification Score 1 points 2 points 3 points Ascites Absent Mildmoderate Serum bilirubin < 2.0 (< 34) (34-50) Severe - refractory > 3.0 (> 50) Serum albumin > < 2.8 g/dl INR < > 2.2 Grade of hepatic encephalopathy none mg/dl (µmol/l) Child -Pugh A Child -Pugh B Child -Pugh C 5 6 points 7 9 points points

10 Grades of hepatic encephalopathy West Haven Criteria Grade Grade 1 Grade 2 Grade 3 Grade 4 definition Trivial lack of awareness Euphoria or anxiety Shortened attention span Impaired performance of addition Lethary or apathy Minimal disorientation for time or place Subtle personality change Inappropriate behaviour Impaired performance of subtraction Somnolence to semistupor, but responsive to verbal stimuli Confusion Gross disorientation Coma (unresponsive to verbal or noxious stimuli) Ferenci et al, Hepatology 2002

11 Exclusion criteria I Female patients being pregnant or breast feeding Females of child-bearing potential must use adequate contraception and must have a negative pregnancy test performed within 7 days prior to inclusion into this study Males not using adequate birth control measures

12 Exclusion criteria II One or more of the following: - Hemoglobin <10g/dL, - WBC <2,500 cells/mm 3, - ANC <1,500 cells/mm 3, - platelets <50,000/mm 3, - ECOG performance status >2

13 Grade definition ECOG performance status 0 Fully active, able to carry on all pre-disease performance without restriction 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light house work, office work 2 Ambulatory and capable of all selfcare but unable to carry out any work acitivities; up and about > 50% of waking hours 3 Capable of only limited selfcare, confined to bed or chair for > 50% of waking hours 4 Completely disabled, cannot carry on any selfcare, totally confined to bed or chair 5 dead

14 Exclusion criteria III Life expectancy <16 weeks Extrahepatic metastases Except metastases to bone, lymph nodes or adrenal glands

15 Exclusion criteria IV Patients with known GFR <30 ml/min/1.73m 2 PT-INR/PTT >1.5 times the upper limit of normal (patients on anticoagulation therapy will be allowed to participate provided that no prior evidence exists of an underlying abnormality in anticoagulation) uncontrolled infections at the time of microtherapy Child-Pugh score > 7 points in patients receiving anticoagulant therapy: Child-Pugh score >5 points (INR category not regarded for calculation of the Child-Pugh score) Uncontrolled ascites

16 Exclusion criteria V tumor load of the whole liver >70% Contraindications for study medications according to product labeling or procedures (sorafenib, Primovist, x- ray contrast agents, SIR-Spheres, RFA/BT, MRI, CT) incl. any contraindication to the trans-arterial interventional procedure (e.g., allergy against x-ray contrast agents, uncontrolled hyperthyroidism)

17 Important contraindications for treatment with sorafenib Intolerance of sorafenib or one of the other ingredients of Nexavar Caveats: Interference of sorafenib with co-medication, e.g. Co-medication with warfarin frequent observation of INR necessary due to increased incidence of bleeding complications Inductors of CYP3A4 (may lower the blood levels of sorafenib)

18 Important contraindications for Primovist Intolerance of Gd-EOB-DTPA or one of the other ingredients of Primovist Caveats: Impaired kidney function e.g. due to hepatorenal syndrome Long QT-syndrome Co-medication with amiodaron, sotalol or other class III anti-arrhythmic therapy

19 Exclusion criteria VI Having undergone Whipple (or similar) surgical procedure Common bile duct stent Significant cardiovascular disease; e.g. myocardial infarction within 6 months of inclusion, chronic heart failure (New York Heart Association class III or IV), unstable coronary artery disease Uncontrolled hypertension Thrombotic or embolic events including transient ischemic attacks within the past 6 months

20 Exclusion criteria VII History of hemorrhage / bleeding events of grade 3 or worse Previous variceal bleeding within the past 3 months Previous malignancy other than carcinoma in situ of the skin or the cervix uteri within 5 years prior to inclusion History of organ transplant (including prior liver transplantation)

21 Exclusion criteria VIII HIV, congenital immune defect, any immunosuppressive therapy for autoimmune disease (rheumatoid arthritis) or inflammatory bowel disease Mental conditions rendering the subject incapable to understand the nature, scope, and consequences of the trial

22 Exclusion criteria IX Close affiliation with the investigational site; e.g. firstdegree relative of the investigator. Participating in another clinical trial or has completed study participation in another clinical trial within 30 days of enrolment into this trial Having been previously enrolled in this clinical trial

23 Additional criteria for the curative treatment group inclusion Not more than 4 HCC lesions in the liver No prior treatment of HCC Maximum diameter of HCC lesion: 5 cm (up to 4 lesions with a maximum diameter of 5 cm each are allowed)

24 Additional criteria for the curative treatment group exclusion Patients in whom surgical resection is the most appropriate treatment Invasion of the portal vein main stem, or invasion of the reight/left portal vein (lobar level)

25 Additional criteria for the palliative treatment group inclusion Not eligible for TACE (at the discretion of the investigator; i.e. diffuse tumors, large tumors) Patients who have undergone prior hepatic treatments (resection, PEI, RFA, TAE or TACE) for HCC are eligible under certain conditions

26 Additional criteria for the palliative treatment group inclusion Resection (segmentectomy, lobectomy) prior RFA and vascular interventions must leave sufficient liver tissue to maintain hepatic functional reserve as indicated by the general inclusion/exclusion criteria Prior TAE and TACE must have been conducted a minimum of three (3) months prior to evaluation for the current study, with sufficient hepatic vascular flow to permit infusion of yttrium-90 microspheres For prior TAE/TACE procedures, there is sufficient hepatic vasculature to access either pre-existing lesion(s) that have revascularized, or there is sufficient collateral flow to new lesions to permit the infusion of yttrium-90 microspheres

27 Additional criteria for the palliative treatment group exclusion Bilirubin above 1.5 times the upper limit of the normal range Hepato-pulmonary shunt leading to a lung dose >30 Gy any previous external beam radiation therapy to the liver Previous therapy with monoclonal antibodies

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29 Thank you for your attention!