Dose Escalation Study of Cabozantinib for Advanced HCC Patients With Preserved Liver Function

NCT04522908 | Completed Phase 2

• 3 other identifiers: CaboRISE2020-000775-20AIO-HEP-0320/ass
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 10

Brief Summary

Open-label, single arm, multicenter phase II trial assessing the tolerability of a reduced starting dose of 40 mg cabozantinib for 4 weeks and subsequent dose escalation to 60 mg cabozantinib until disease progression or intolerable toxicities.

Conditions

Hepatocellular Carcinoma (HCC); Second Line Treatment

Keywords

hepatocellular carcinoma; HCC; Child-Pugh A

Outcome Measures

Primary Outcomes (1)

• Treatment discontinuation rate due to treatment-related adverse events

  Any unresolved intolerable Grade 2 TRAE or unresolved Grade ≥ 3 TRAE after 60 mg or 40 mg or any intolerable Grade 2 TRAE or Grade ≥ 3 TRAE after 20 mg will count as treatment discontinuation due to AE.

  27 months

Secondary Outcomes (8)

• Overall survival

  27 months

• Progression free survival (PFS) according to RECIST 1.1

  at 10 weeks

• Objective response rate (ORR) according to RECIST 1.1

  27 months

• Time on treatment

  27 months

• Treatment exposure

  27 months

Study Arms (1)

Cabozantinib - Single Arm

EXPERIMENTAL

Single Arm with Cabozantinib starting dose 40 mg for 4 weeks and dose escalation to 60 mg afterwards.

Drug: Cabozantinib Oral Tablet

Interventions

Cabozantinib Oral Tablet DRUG

Cabozantinib starting dose of 40 mg, oral, once daily for 4 weeks followed by Cabozantinib escalated dose of 60 mg, oral, once daily from week 5 onwards

Also known as: CABOMETYX

Cabozantinib - Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients with HCC who have been previously treated with any first line therapy.
• 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.
• Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and/or locoregional therapies.
• 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.
• Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.
• For women of childbearing potential (WOCBP): 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.

You may not qualify if:

• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 4 months.
• Significant portal hypertension (moderate or severe ascites). Significant hypertension, defined as blood pressure ≥ 140 mmHg (systolic) or ≥ 90 mmHg (diastolic) in repeated measurements.
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• Patients with impaired liver function defined as Child-Pugh B or C, if liver cirrhosis is present.
• Severely impaired kidney function (defined as creatinine \> 2 mg/dl and/or creatinine clearance \< 45 mL/min).
• Elevations of AST/ALT \> 5 x ULN at baseline.
• Presence of encephalopathy in past 12 months.
• 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.
• Baseline QTcF \> 500 ms.
• 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.
• 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.
• 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.
• Prior cabozantinib use.
• Known or suspected hypersensitivity to cabozantinib or any other excipients of the IMP.

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• Johann Wolfgang Goethe University Hospital, Prof. Dr. med. Trojan: collaborator

Study Sites (10)

HELIOS Klinikum Bad Saarow

Bad Saarow, Germany

Location

Universitätsklinikum Köln AöR

Cologne, 50937, Germany

Location

BAG / Onkologische Gemeinschaftspraxis

Dresden, Germany

Location

Ev. Kliniken Essen-Mitte, Klinik für Internistische Onkologie

Essen, 45136, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Institute for Clinical Cancer Research Krankenhaus Nordwest

Frankfurt, 60488, Germany

Location

Klinikum der Johann-Wolfgang-Goethe Universität

Frankfurt, Germany

Location

Universitätsklinikum Gießen und Marburg

Giessen, 35392, Germany

Location

Universität Leipzig KöR, Medizinische Fakultät Department für Innere Medizin, Neurologie Klinik für Gastroenterologie

Leipzig, Germany

Location

Klinikum rechts der Isar Technische Universität München Klinik und Poliklinik für Innere Medizin II

Müchen, Germany

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Salah-Eddin Al-Batran, Prof. Dr.

  Frankfurter Institut fuer Klinische Krebsforschung IKF GmbH

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Clinical trials with a single arm, all eligible patients will receive Cabozantinib starting dose of 40 mg, oral, once daily for 4 weeks, followed by Cabozantinib escalated dose of 60 mg, oral, once daily from week 5 onwards

Study Record Dates

• First Submitted: August 3, 2020
• First Posted: August 21, 2020
• Study Start: October 12, 2020
• Primary Completion: October 4, 2024
• Study Completion: October 4, 2024
• Last Updated: January 30, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (10)