A Study to Evaluate the Safety, Tolerability and Efficacy of Cabozantinib in Patients With Hepatocellular Carcinoma and Impaired Liver Function
- Registration Number
- NCT04454762
- Lead Sponsor
- Johannes Gutenberg University Mainz
- Brief Summary
This is an prospective, interventional, non-randomized multicenter phase II study to evaluate the safety, tolerability and efficacy of Cabozantinib as a second-line therapy (after one prior systemic therapy) in patients with intermediate to advanced HCC (BCLC B/C) and concomitant impaired liver function CP score B7-8. Subjects who meet all study eligibility criteria will receive Cabozantinib 40 mg daily orally. Subjects will receive Cabozantinib as long as they continue to experience clinical benefit in the opinion of the Investigator or until there is unacceptable toxicity or the need for subsequent systemic anti-cancer treatment or liver directed local anti-cancer therapy. Treatment may continue in this fashion after radiographic progression as long as the Investigator believes that the subject is still receiving clinical benefit from Cabozantinib and that the potential benefit of continuing Cabozantinib outweighs potential risk. In addition, all subjects will be treated with best supportive care. This excludes systemic anti-cancer therapy and liver-directed local anti-cancer therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 20
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cabozantinib Cabozantinib 40 mg cabozantinib oral daily. When dose reduction is necessary, it is recommended to reduce to 20 mg daily.
- Primary Outcome Measures
Name Time Method Blood pressure [Safety and Tolerability] Through study completion, up to approximately 2 years. mmHg
Incidence of Adverse Events (AEs) [Safety and Tolerability] Through study completion, up to approximately 2 years An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be presented.
Number of Participants Who Discontinue Study Treatment Due to Adverse Events (AEs) [Safety and Tolerability] Through study completion, up to approximately 2 years The number of participants who discontinue study treatment due to an AE will be presented.
ALBI [Safety and Tolerability] Through study completion, up to approximately 2 years Assessment of the Albumin-Bilirubin (ALBI) Grade. Grade range 1-3, with 3 indicating greatest severity
ECOG [Safety and Tolerability] Through study completion, up to approximately 2 years Eastern Cooperative Oncology Group (ECOG) performance status. Score range 0 (normal activity) to 5 (dead).
Child-Pugh [Safety and Tolerability] Through study completion, up to approximately 2 years Used to assess the prognosis of chronic liver disease. Classification of severity of liver disease according to the degree of ascites, total bilirubin and albumin, prothrombin time, and degree of encephalopathy. Each measure is scored 1-3, with 3 indicating greatest severity
- Secondary Outcome Measures
Name Time Method Overall survival (OS) Through study completion, up to approximately 2 years The time between first application of trial medication to date of death due to any cause.
Progression-free survival (PFS) Through study completion, up to approximately 2 years PFS is defined as the time from first intake of trial medication to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm.
Objective response rate (ORR) Through study completion, up to approximately 2 years The response rate is defined as the percentage of subjects with a confirmed reduction in tumor size compared to baseline as well as fulfilling the criteria for complete or partial response according to RECIST 1.1.
Pharmacokinetics (PK) of Cabozantinib administration. 6 weeks The plasma concentration of Cabozantinib and possible relevant metabolites will be measured in PK samples.
Health-related quality of life (HRQOL) Through study completion, up to approximately 2 years Assessed by the validated German version of the Chronic Liver Disease Questionnaire (CLDQ-D). The questionnaire contains 29 items which can be grouped into the liver-disease specific domains like activity, fatigue, worries, abdominal symptoms, and systemic symptoms. Each category can be judged separately between the groups. The results of the CLDQ-D score are presented on a 7-point Likert scale. Higher results indicate better quality of life.
Trial Locations
- Locations (1)
Department of Internal Medicine I, Johannes Gutenberg University Mainz
🇩🇪Mainz, Germany