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

STATUS

Recruiting
End date

Sep 26, 2023
participants needed

40
sponsor

Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Updated on 26 April 2022

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progressive disease

cabozantinib

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.

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Patients will be recruited from up to 10 sites and patients withdrawn from the trial will not be replaced.

Details

Condition	Hepatocellular Carcinoma (HCC), Second Line Treatment
Treatment	Cabozantinib Oral Tablet
Clinical Study Identifier	NCT04522908
Sponsor	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Last Modified on	26 April 2022

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Eligibility		Yes	No	Not Sure
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 diagnosis confirmed by histology/cytology or clinically by guideline criteria in cirrhotic patients
	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]

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