Cabozantinib for Patients with Hepatocellular Carcinoma (HCC) Refractory to First Line Treatment

Prior treatment

• Prior sorafenib treatment.
• 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.
• 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.
• 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.
• Treatment with investigational systemic therapy within 28 days prior to initiation of study treatment.
• Prior cabozantinib use.
• 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.

Other illness

• Significant portal hypertension (moderate or severe ascites).
• History of encephalopathy in past 12 months, if not completely regressive or more than one episode within the last 6 months.

Lab values

• Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.
• 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.
• Elevations of AST/ALT exceeding 5 X ULN.

Other

• Unwillingness to give informed consent for participation in the study.
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 5 months after last dose of study treatment.
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• Liver cirrhosis Child-Pugh B with \> 7 points and Child-Pugh C.
• Severely impaired kidney function.
• Baseline QTcF \>500 ms.
• Patients who have been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.
• 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 \[§ 40 Abs. 1 S. 3 Nr. 3a AMG\].

• Fully-informed written consent.
• 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.
• Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/ cytology or clinically by guideline criteria in cirrhotic patients
• Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and /or locoregional therapies.
• 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.
• ECOG performance status ≤ 2.
• Resolution of any acute, clinically significant treatment-related toxicity from prior therapy to Grade 1 prior to study entry, with the exception of alopecia.
• 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.