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Hepatocellular Carcinoma (HCC)Phase 2NCT04522908

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

A Phase 2 study testing Cabozantinib Oral Tablet in people with Hepatocellular Carcinoma (HCC) and Second Line Treatment, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 10 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cabozantinib Oral Tablet
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
10 sitesGermany
Study dates
12 Oct 2020to 4 Oct 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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].

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Germany10 sites

  • HELIOS Klinikum Bad Saarow

    Bad Saarow

  • Universitätsklinikum Köln AöR

    Cologne, 50937

  • BAG / Onkologische Gemeinschaftspraxis

    Dresden

  • Ev. Kliniken Essen-Mitte, Klinik für Internistische Onkologie

    Essen, 45136

  • Universitätsklinikum Essen

    Essen, 45147

  • Institute for Clinical Cancer Research Krankenhaus Nordwest

    Frankfurt, 60488

  • Klinikum der Johann-Wolfgang-Goethe Universität

    Frankfurt

  • Universitätsklinikum Gießen und Marburg

    Giessen, 35392

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

    Leipzig

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

    Müchen

Other trials in Germany

About this study

Official title: 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.

Read the 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.

Being tested
Cabozantinib Oral Tablet
Keywords
hepatocellular carcinoma, HCC, Child-Pugh A
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cabozantinib Oral TabletDrug

    Also called CABOMETYX

    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 groups in NCT04522908
Study groupRoleWhat they receive
Cabozantinib - Single ArmExperimentalSingle Arm with Cabozantinib starting dose 40 mg for 4 weeks and dose escalation to 60 mg afterwards.
Receives: Drug: Cabozantinib Oral Tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 27 months

Secondary outcomes (8)

  1. Overall survival

    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.

    Measured: 27 months

  2. Progression free survival (PFS) according to RECIST 1.1

    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.

    Measured: at 10 weeks

  3. Objective response rate (ORR) according to RECIST 1.1

    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.

    Measured: 27 months

  4. Time on treatment

    Time on treatment defined as the interval from therapy initiation until premature discontinuation.

    Measured: 27 months

  5. Treatment exposure

    Treatment exposure defined as summary of specific dose intensities on treatment (including dose reductions and interruptions).

    Measured: 27 months

  6. Treatment-related and -unrelated toxicities (AEs, SAEs) according to NCI CTCAE v5.0

    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.

    Measured: 27 months

  7. Quality of Life with the EORTC QLQ-C30 patient questionnaire

    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.

    Measured: 27 months

  8. Correlation of biomarkers potentially associated with clinical efficacy (OS, PFS and ORR)

    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.

    Measured: 27 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Aug 2020
  2. Study start12 Oct 2020
  3. Primary completion4 Oct 2024
  4. Study completion4 Oct 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04522908
Sponsor's protocol ID
CaboRISE
Other IDs
2020-000775-20, AIO-HEP-0320/ass
Status last verified
Jan 2025
First submitted
3 Aug 2020
Last updated
30 Jan 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No IPD will be shared

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib Oral Tablet in people with Hepatocellular Carcinoma (HCC) and Second Line Treatment, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 10 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment discontinuation rate due to treatment-related adverse events (time frame: 27 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04522908.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2025.

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