Study to evaluate the safety, tolerability and efficacy of Cabozantinib in patients with hepatocellular carcinoma and impaired liver function.
- Conditions
- Hepatocellular carcinoma (HCC)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001075-36-DE
- Lead Sponsor
- niversitätsmedizin Mainz
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 20
1. Written informed consent
2. Age 18
3. Histological/cytological or non-invasive (according to EASL/AASLD guidelines) diagnosis of HCC
4. Availability of a recent (up to 28 days old) CT/MRI images of thorax and abdomen
5. Subject’s HCC is not amenable to a curative treatment approach (e.g., transplant, surgery, radiofrequency ablation) corresponding to BCLC
classification B/C.
6. Progression or toxicities following one prior systemic therapy for HCC
7. Recovery to = grade 1 from toxicities related to any prior treatments, unless the adverse events are clinically non-significant and/or stable on
supportive therapy
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
9. Adequate hematologic function, based upon meeting the following laboratory criteria within 7 days before enrollment:
• absolute neutrophil count (ANC) = 1200/mm3 (= 1.2 x 109/L)
• platelets = 60,000/mm3 (= 60 x 109/L)
• hemoglobin = 8 g/dL (= 80 g/L)
10. Adequate renal function, based upon meeting the following laboratory criteria within 7 days before enrollment: serum creatinine = 1.5 × upper limit of normal or calculated creatinine clearance = 40 mL/min (using the Cockcroft-Gault equation)
11. Liver function Child-Pugh (CP) score B7-8
12. ALBI (albumin-bilirubin) grade 1-2
13. Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) < 7.0 × upper limit of normal (ULN) within 7 days before enrollment
14. Antiviral therapy per local standard of care if active hepatitis B (HBV) infection
15. Capability to understand and comply with the protocol requirements (e.g. sufficient knowledge of German language to answer the questionnaires ability to swallow intact tablets).
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 5
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
1. Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
2. Receipt of more than 1 prior systemic therapy for advanced HCC. Additional prior systemic therapies used as adjuvant or local therapy are allowed.
3. Any type of anti-cancer agent (including investigational) within 2 weeks before enrollment
4. Radiation therapy within 4 weeks (2 weeks for radiation for bone metastases) or radionuclide treatment (e.g., I-131 or Y-90) within 6 weeks of enrollment. Subject cannot be enrolled 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 enrollment. Eligible subjects must be without corticosteroid treatment at the time of enrollment.
7. Concomitant anticoagulation, at therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, low molecular weight Heparin (LMWH), thrombin or activated coagulation factor X (FXa) inhibitors, or antiplatelet agents (e.g., 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.
9. Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding are excluded with the following clarification: subjects with history of prior variceal bleeding must have been treated with adequate endoscopic therapy without any evidence of recurrent bleeding for at least 6 months prior to study entry and must be stable on optimal medical management (e.g. non-selective beta blocker, proton pump inhibitor) at study entry.
10. Women who are pregnant, nursing, or who plan to become pregnant while in the Trial.
11. Women of child-bearing potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly beginning at informed consent, for the duration of study participation and for at least 4 months after last dose of the study drug. Because oral contraceptives might possibly not be considered as effective Methods of contraception during the Treatment with cabozantinib, they should be used together with another method, such as a barrier method.
12. Currently receiving any other investigational agent or received an investigational agent within 30 days (or within 5 times the half-life of this agent or its relevant Metabolits, the longer period apply) before the first dose of Cabozantinib.
13. Hepatic encephalopathy Grad I-IV according to CP classification (= 2 points) and West Haven Criteria.
14. Moderate or severe ascites according to CP classification (= 3 points).
15. Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 7 days before enrollment.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The objective of this study is 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.;Secondary Objective: Not applicable;Primary end point(s): Safety and tolerability of Cabozantinib administration in HCC patients with impaired liver function CP score B7-8, assessed by adverse events, laboratory values, vital signs, Child-Pugh class/score, ALBI score and ECOG performance Status.;Timepoint(s) of evaluation of this end point: Through study completion, up to approximately 2 years.
- Secondary Outcome Measures
Name Time Method