livercell cancer malignant hepatoma
Conditions
Interventions
Subjects will take blinded study medication (tablets containing 60 mg of
cabozantinib or placebo equivalent) once daily orally at bedtime. Required dose
reductions will be in decrements of 20 mg cab
Sponsors
Exelixis Inc
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Histologische of cytologische diagnose van HCC (resultaten van een voorafgaand biopt wordt geaccepteerd) 2. De proefpersoon heeft een ziekte die niet ontvankelijk is voor een curatieve behandelingsmethode (bv. transplantatie, operatie, radiofrequente ablatie) 3. Eerder behandeld met sorafenib 4. Progressie volgend op tenminste 1 eerdere systemische behandeling voor HCC 5. Herstel tot * graad 1 van toxische effecten van eerdere behandelingen, tenzij de bijwerkingen klinisch niet significant zijn en/of stabiel zijn bij ondersteunende behandeling 6. Leeftijd * 18 jaar op de dag van toestemming 7. ECOG-performancestatus van 0 of 1 8. Adequate hematologische functie, gebaseerd op het voldoen aan de volgende laboratoriumcriteria binnen 7 dagen voor randomisatie: a. absolute aantal neutrofielen (ANC) * 1200/mm3 (* 1,2 x 109/l) b. bloedplaatjes * 60.000/mm3 (* 60 x 109/l) c. hemoglobine * 8 g/dl (* 80 g/l) 9. Adequate nierfunctie, gebaseerd op het voldoen aan de volgende laboratoriumcriteria binnen 7 dagen voor randomisatie: a. serumcreatinine * 1,5 x de bovengrens van normaal of een berekende creatinineklaring * 40 ml/min (gebruikmakend van de Cockroft-Gault-vergelijking: (140 * leeftijd) x gewicht (kg)/(serumcreatinine × 72 [mg/dl]) voor mannen. (Voor vrouwen vermenigvuldigen met 0,85.) EN b. urinaire eiwit/creatinine-verhouding (*urine protein/creatinine ratio*, UPCR) * 1 mg/mg (* 113,1 mg/mmol) of eiwit in 24-uurs urine
Exclusion criteria
Exclusion criteria: 1. Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma 2. Receipt of more than 2 prior systemic therapies for advanced HCC. Additional prior systemic therapies used as adjuvant or local therapy are allowed. 3. Any type of anticancer agent (including investigational) within 2 weeks before randomization 4. Radiation therapy within 4 weeks (2 weeks for radiation for bone metastases) or radionuclide treatment (eg, I-131 or Y-90) within 6 weeks of randomization. Subject is excluded if there are any clinically relevant ongoing complications from prior radiation therapy. 5. Prior cabozantinib treatment 6. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before randomization. Eligible subjects must be without corticosteroid treatment at the time of randomization. 7. Concomitant anticoagulation, at therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, low molecular weight heparin (LMWH), thrombin or coagulation factor X (FXa) inhibitors, or antiplatelet agents (eg, clopidogrel). Low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (* 1 mg/day), and low-dose LMWH are permitted. 8. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: a. Cardiovascular disorders including i. Symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias ii. Uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic, or > 100 mm Hg diastolic despite optimal antihypertensive treatment iii. Stroke (including TIA), myocardial infarction, or other ischemic event within 6 months before randomization iv. Thromboembolic event within 3 months before randomization. Subjects with thromboses of portal/hepatic vasculature attributed to underlying liver disease and/or liver tumor are eligible b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i. Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction ii. Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months before randomization, Note: Complete healing of an intra-abdominal abscess must be confirmed prior to randomization c. Major surgery within 2 months before randomization. Complete healing from major surgery must have occurred 1 month before randomization. Complete healing from minor surgery (eg, simple excision, tooth extraction) must have occurred at least 7 days before randomization. Subjects with clinically relevant complications from prior surgery are not eligible d. Cavitating pulmonary lesion(s) or endobronchial disease e. Lesion invading a major blood vessel including but not limited to : inferior vena cava, pulmonary artery, or aorta). Subjects with lesions invading the portal vasculature are eligible. f. Clinically significant bleeding risk including the following within 3 months of randomization: hematuria, hematemesis, hemoptysis of >0.5 teaspoon (>2.5 mL) of red blood, o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoint: Overall survival (OS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints: * Objective response rate (ORR) per RECIST 1.1 * Progression-free survival (PFS) per RECIST 1.1 Additional endpoints: * Safety and tolerability * Pharmacokinetics (PK) * Relationship of baseline and changes in biomarkers with treatment and/or clinical outcome * Health-related quality of life (HRQOL) as assessed by the EuroQol Health questionnaire instrument (EQ-5D-5L) | — |
Countries
Netherlands
Outcome results
None listed