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

January 28, 2025 updated by: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

A Phase II Study Evaluating Reduced Starting Dose and Dose Escalation of Cabozantinib As Second-line Therapy for Advanced HCC in Patients with Preserved Liver Function

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The primary objective is to assess the tolerability of a reduced starting dose of 40 mg cabozantinib once-daily for 4 weeks and subsequent dose escalation to 60 mg cabozantinib once-daily to be maintained until disease progression or intolerable toxicities. Using the same study treatment discontinuation criteria as in the pivotal CELESTIAL trial will allow for comparison of treatment discontinuation rates due to treatment related adverse events (TRAEs) defined as unresolved intolerable Grade 2 TRAEs or any unresolved Grade 3 TRAEs (see Section 6).

Patients eligible for this trial are HCC patients with preserved liver function previously treated with any first line therapy.

Secondary objectives comprise the assessment of overall survival (OS), progression free survival (PFS) at 10 weeks, objective response rate (ORR), time on treatment, treatment exposure (dose intensity/dose reductions), toxicity, and quality of life (QLQ-C30).

In addition, tissue samples (optional) will be analyzed for molecular parameters and immune cell composition to identify biomarkers potentially associated with clinical efficacy (OS, PFS and ORR).

This is an open label, single-arm, multicenter phase II trial. 40 patients suffering from advanced stage hepatocellular carcinoma (HCC) with preserved liver function in second line treatment, after any first line therapy, will be enrolled in this trial.

Patients will be recruited from up to 10 sites and patients withdrawn from the trial will not be replaced.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Germany
      • Bad Saarow, Germany
        • Helios Klinikum Bad Saarow
      • Dresden, Germany
        • BAG / Onkologische Gemeinschaftspraxis
      • Essen, Germany, 45147
        • Universitatsklinikum Essen
      • Essen, Germany, 45136
        • Ev. Kliniken Essen-Mitte, Klinik für Internistische Onkologie
      • Frankfurt, Germany, 60488
        • Institute for Clinical Cancer Research Krankenhaus Nordwest
      • Frankfurt, Germany
        • Klinikum der Johann-Wolfgang-Goethe Universität
      • Gießen, Germany, 35392
        • Universitätsklinikum Gießen und Marburg
      • Köln, Germany, 50937
        • Universitätsklinikum Köln AöR
      • Leipzig, Germany
        • Universität Leipzig KöR, Medizinische Fakultät Department für Innere Medizin, Neurologie Klinik für Gastroenterologie
      • Müchen, Germany
        • Klinikum rechts der Isar Technische Universität München Klinik und Poliklinik für Innere Medizin II

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Rare hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
  • Is currently participating in 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.
  • Patient who has 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].

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cabozantinib - Single Arm
Single Arm with Cabozantinib starting dose 40 mg for 4 weeks and dose escalation to 60 mg afterwards.
Drug: Cabozantinib Oral Tablet
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
Other Names:
  • CABOMETYX

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Treatment discontinuation rate due to treatment-related adverse events
Time Frame: 27 months
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 27 months
Time from the date of enrollment to the date of death from any cause. Subjects who have not died by the date of data cutoff will be right censored at the last known date alive.
27 months
Progression free survival (PFS) according to RECIST 1.1
Time Frame: at 10 weeks
Time from the date of enrollment to the date of first observed disease progression (investigator assessment according to RECIST 1.1) or death from any cause. Subjects who have died without a reported disease progression will be considered to have progressed on the date of their death. Subjects who did not progress or have died will be right censored on the date of their last evaluable tumor assessment.
at 10 weeks
Objective response rate (ORR) according to RECIST 1.1
Time Frame: 27 months
Objective response rate will be assessed according to RECIST 1.1 (refer to Appendix 5). Objective response rate will be defined as the proportion of subjects experiencing a confirmed complete response (CR) or confirmed partial response (PR) per RECIST 1.1.
27 months
Time on treatment
Time Frame: 27 months
Time on treatment defined as the interval from therapy initiation until premature discontinuation.
27 months
Treatment exposure
Time Frame: 27 months
Treatment exposure defined as summary of specific dose intensities on treatment (including dose reductions and interruptions).
27 months
Treatment-related and -unrelated toxicities (AEs, SAEs) according to NCI CTCAE v5.0
Time Frame: 27 months
All observed treatment-related and -unrelated toxicities (type, incidence and severity of AEs and SAEs) and side effects will be graded according to NCI CTCAE v5.0 and the degree of association of each with the study treatment assessed and summarized. The treatment related serious adverse events rate (SAE) will be determined.
27 months
Quality of Life with the EORTC QLQ-C30 patient questionnaire
Time Frame: 27 months
Patient reported outcome assessed by the validated EORTC patient quality of life questionnaire QLQ-C30. The questionnaire evaluates the patient's health and activities in everyday life. Values reach from 1 (not at all) to 4 (very much). Low values mean a better outcome.
27 months
Correlation of biomarkers potentially associated with clinical efficacy (OS, PFS and ORR)
Time Frame: 27 months

The TR projects might include the assessment of the following:

FFPE tissue for IHC staining; FFPE tissue for nucleic isolation to assess the expression of biomarkers, determination of genetic alterations in HCC (panel sequencing) or to determine the mutational load.
27 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Johann Wolfgang Goethe University Hospital, Prof. Dr. med. Trojan

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Salah-Eddin Al-Batran, Prof. Dr., Frankfurter Institut fuer Klinische Krebsforschung IKF GmbH

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 12, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 4, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 4, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 3, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 18, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 21, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 28, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CaboRISE
  • 2020-000775-20 (EudraCT Number)
  • AIO-HEP-0320/ass (Other Identifier: Arbeitsgemeinschaft Internistische Onkologie)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No IPD will be shared

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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