Locally advanced or metastatic and/or unresectable HCC
Conditions
Interventions
Product Name: Cabozantinib
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Cabozantinib
CAS Number: 1140909-48-3
Other descriptive name: Cabozantinib S-malate
Concentration unit: mg milli
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. Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/ cytology or clinically by guideline criteria in cirrhotic patients 4. Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and /or locoregional therapies. 5. Patients who have shown progressive disease during or after first line therapy OR patients must have had their treatment interrupted due to the level of toxicities AND cabozantinib therapy is intended as second line therapy. 6. ECOG performance status = 2. 7. Resolution of any acute, clinically significant treatment-related toxicity from prior therapy to Grade 1 prior to study entry, with the exception of alopecia. 8. For women of childbearing potential and men who are sexually active with women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods. 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 25
Exclusion criteria
Exclusion criteria: 1. Unwillingness to give informed consent for participation in the study. 2. Prior sorafenib treatment. 3. Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 5 months after last dose of study treatment. 4. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment. 5. Significant portal hypertension (moderate or severe ascites). 6. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC. 7. Liver cirrhosis Child-Pugh B with > 7 points and Child-Pugh C. 8. Severely impaired kidney function. 9. History of encephalopathy in past 12 months, if not completely regressive or more than one episode within the last 6 months. 10. Significant cardiovascular disease (such as New York Heart Association 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. 11. Baseline QTcF >500 ms. 12. 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. 13. 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. 14. 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. 15. Elevations of AST/ALT exceeding 5 X ULN. 16. Treatment with investigational systemic therapy within 28 days prior to initiation of study treatment. 17. Prior cabozantinib use. 18. Is currently participating 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. 19. Patients who have been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG. 20. 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 Time-on-Treatment with cabozantinib in lenvatinib (lenvatinib monotherapy or lenvatinib-IO combination therapy) pre-treated patients with locally advanced and/or metastatic and/or unresectable Hepatocellular Carcinoma (HCC).;Secondary Objective: Secondary efficacy objectives are overall survival, progression free survival, objective response rate, duration of response and treatment exposure (time on treatment/dose intensity/dose reductions). Changes in ECOG performance status, ALBI score and Child-Pugh score over the course of treatment are also determined. Furthermore, safety and tolerability are being evaluated including the assessment of treatment-related adverse events (TRAEs) that lead to treatment interruptions, modification or discontinuations. ;Primary end point(s): The primary efficacy endpoint is: •Time-on-Treatment ;Timepoint(s) of evaluation of this end point: End of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints will include: • Overall survival (OS) • Progression free survival (PFS) • Objective response rate (ORR) according to RECIST 1.1 • Duration of response (DOR) • Treatment exposure (time on treatment/dose intensity/dose reductions) • Toxicity: o Treatment-related adverse events (TRAEs) o TRAE related treatment interruptions o TRAE related treatment modifications o TRAE related treatment discontinuations • Change in ECOG Performance Status during treatment • Change in ALBI Grade during treatment • Change in Child Pugh Score during treatment • Translational research: correlation of biomarkers potentially associated with clinical efficacy (OS, PFS and ORR) of cabozantinib by o NGS Oncopanel analysis o VEGF module expression analysis. ;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