Advanced (localized disease but surgically unresectable or metastatic) histologically/cytologically proven hepatocellular carcinoma (or hepatic lesion and aFP ³ 400 ng/ml). MedDRA version: 8.1 Level: LLT Classification code 10007284 Term: Carcinoma
Conditions
Interventions
Product Name: Sutent
Product Code: SU 11248
Pharmaceutical Form: Tablet
Sponsors
Policlinico Universitario Agustino Gemelli
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all of the following inclusion criteria to be eligible for enrollment into the trial: 1. Advanced (localized disease but surgically unresectable or metastatic) histologically/cytologically proven hepatocellular carcinoma (or hepatic lesion and aFP ³ 400 ng/ml). 2. No prior chemotherapy for metastatic disease. 3. No previous local treatment (RF, PEI, CE) on target lesions. 4. No previous immunotherapy. 5. Adequate bone marrow function as defined by: ? ANC =1500 cells/mm3. ?? Platelets =75, 000 cells/mm3. ? ?Hemoglobin =9 g/dL (which may be obtained by transfusion or growth factor support. 6. Adequate liver function as defined by: ?? Bilirubin =1.5 times upper limit of normal (x ULN). ? ?AST and ALT = 3 x ULN. ? ?Alkaline phosphate = 3 x ULN. 7. Adequate renal function as defined by both: ? ?Serum creatinine =1.5 x ULN. 8. No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart on the same day (The baseline systolic blood pressure readings must be less than or equal to 140 mm Hg, and the baseline diastolic blood pressure readings must be less than or equal to 90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible). 9. ECOG performance status of 0, 1, or 2 (See Appendix 1). 10. Life expectancy =12 weeks. 11. Adults =18 years of age. 12. Negative serum or urine pregnancy test for women of child-bearing potential. 13. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the trial patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Prior treatment with any chemotherapy agent, VEGF/VEGFR inhibitors, or anti-angiogenesis treatment. 2. Patients with locally advanced disease who are candidates for a radical surgical treatment. 3. Current use or anticipated need for drugs that are known CYP3A4 inhibitors (ie, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, ergot derivatives, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, and delavirdine) during the course of study. 4. Current use or anticipated need for drugs that are known CYP3A4 or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, primidone, rifabutin, rifampin, and St John’s wort) during the course of study. 5. Requirement of anticoagulant therapy except for low-dose anticoagulants for maintenance of patency of central venous access or prevention of deep vein thrombosis (DVT). 6. Uncontrolled brain metastases (a controlled brain metastasis must be previously treated, asymptomatic, and without growth for 4 months). 7. Inability to take oral medications. 8. History of hemorrhagic or thrombotic cerebrovascular event in the past 12 months. 9. Major surgical procedure within 4 weeks of treatment. 10. Unstable or severe intercurrent medical condition that, in the opinion of the investigator, might interfere with achievement of study objectives. 11. Psychological or sociological conditions, addictive disorders, or family problems, whichwould preclude compliance with the protocol. 12. History of a malignancy (other than hepatocellular carcinoma) except those patients treated with curative intent for skin cancer (other than melanoma) or in situ cervical cancer or those treated with curative intent for any other cancer with no evidence of disease. 13. Patients having procreative potential who are not taking careful precautions to prevent pregnancy 14. Women who are pregnant or breast-feeding. 15. Patients with proteinuria. (Patients with >1+ protein on urine dipstick at baseline should undergo a 24-hour urine collection. Results must demonstrate =500 mg of protein in 24 hours to allow participation in the study. 16. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary The primary end point is response rate, assessed with CT-scan according to RECIST criteria, decrease of the alphafetoprotein serun levels, decrease of FDG captation at PET-scan. All deaths from any cause will be included in the analysis. ;Secondary Objective: Secondary 1. Safety profile of treatments based on physical examinations, laboratory tests, and assessment of adverse events 2. Time to progression, based on progression or death from any cause. 3. Time to treatment failure, based on the treatment withdrawn of any cause. 4. One year survival, based on the proportion of patients still alive 1 year after inclusion. 5. Patient-reported outcomes of health-related quality of life and liver cancer-specific symptoms, as measured by the EORTC QLQ-C30 and QLQ-PAN26. ;Primary end point(s): This is a Phase 2, multicenter study of the angiogenesis inhibitor SU11248 for patients who have not received prior chemotherapy for locally advanced (surgically unresectable) or metastatic hepatocellular. Objective response rate will be the primary endpoint. A fist cohort of 16 patients is planned; if at least one response is observed, further 16patients will be enrolled. Patients will have assessments for tumor response approximately every 8 weeks. | — |
Countries
Denmark, Italy
Outcome results
None listed