Advanced stage hepatocellular carcinoma (HCC) patients with preserved liver function in second line therapy
Conditions
Interventions
Trade Name: Cabometyx
Product Name: Cabozantinib
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Cabozantinib
CAS Number: 1140909-48-3
Other descriptive name: Cabozantinib S-malate
Concen
Sponsors
Frankfurter Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Fully-informed written consent. 2. Males and females = 18 years of age. *There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the study gender-independently. 3. Patients with HCC who have been previously treated with any first line therapy. 4. Locally advanced or metastatic and/or unresectable HCC with preserved liver function (Child-Pugh A only, if liver cirrhosis is present) with diagnosis confirmed by histology/cytology or clinically by guideline criteria. 5. Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and/or locoregional therapies. 6. Resolution of any acute, clinically significant treatment-related toxicity from prior therapy to Grade 1 prior to study entry, with the exception of alopecia. 7. ECOG performance status = 2. 8. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment. 9. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods from the time of signing the informed consent through at least 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse. Male patients, even if surgically sterilized (i.e. status post-vasectomy) must agree to practice effective barrier contraception (e.g. condom) and to refrain from sperm donation during the entire study treatment period and through at least 4 months after the last dose of study drug or agree to completely abstain from heterosexual intercourse. 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 4 months. 2. Significant portal hypertension (moderate or severe ascites). Significant hypertension, defined as blood pressure = 140 mmHg (systolic) or = 90 mmHg (diastolic) in repeated measurements. 3. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC. 4. Patients with impaired liver function defined as Child-Pugh B or C, if liver cirrhosis is present. 5. Severely impaired kindey function (defined as creatinine > 2mg/dl and/or creatinine clearance 5 x ULN at baseline. 7. Presence of encephalopathy in past 12 months. 8. Significant cardiovascular disease (such as NYHA Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina. 9. Baseline QTcF > 500 ms. 10. Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study. 11. Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia. 12. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications. 13. Treatment with investigational systemic therapy within 28 days or five times the elimination half-life of the investigational product, whichever is longer, prior to initiation of study treatment. 14. Prior cabozantinib use. 15. Known or suspected hypersensitivity to cabozantinib or any other excipients of the IMP. 16. Rare hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. 17. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. 18. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG. 19. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess the tolerability of a reduced starting dose of 40 mg cabozantinib once-daily for 4 weeks and subsequent dose escalation to 60 mg cabozantinib once-daily to be maintained until disease progression or intolerable toxicities. ;Secondary Objective: Secondary objectives comprise the assessment of overall survival (OS), progression free survival (PFS) at 10 weeks, objective response rate (ORR), time on treatment, treatment exposure (dose intensity/dose reductions), toxicity, and quality of life (QLQ-C30). In addition, blood samples and tissue samples (optional) will be analyzed for molecular parameters and immune cell composition to identify biomarkers potentially associated with clinical efficacy (OS, PFS and ORR).;Primary end point(s): The Treatment discontinuation rate due to treatment-related adverse events ;Timepoint(s) of evaluation of this end point: End of Study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall survival (OS) • Progression free survival (PFS) at 10 weeks according to RECIST 1.1 • Objective response rate (ORR) according to RECIST 1.1 • Time on treatment • Treatment exposure (dose intensity/dose reductions) • Toxicity • QoL (QLQ-C30) • Correlation of biomarkers potentially associated with clinical efficacy (OS, PFS and ORR);Timepoint(s) of evaluation of this end point: End of Study | — |
Countries
Germany
Contacts
Public ContactIKF
Frankfurter Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest
Outcome results
None listed