Cabozantinib for Patients with Hepatocellular Carcinoma (HCC) Refractory to First Line Treatment

NCT04511455 | Completed Phase 2

• 4 other identifiers: AURORA2019-004728-39AIO-HEP-0419/assIKF-t018
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 10

Brief Summary

Patients suffering from advanced stage hepatocellular carcinoma (HCC) who have shown disease progression during lenvatinib-based first line treatment, will be enrolled in this trial. Patients who progressed either during lenvatinib monotherapy or lenvatinib-IO (immuno-oncology) combination therapy will be eligible for study participation, whereas at least 50% of the enrolled patients should be in favor of lenvatinib monotherapy.

Conditions

Hepatocellular Carcinoma Non-resectable; Metastatic Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Time-on-treatment

  Time on treatment will be assessed as time from date of first dose of cabozantinib intake till date of permanent discontinuation of treatment.

  at study end (approx. 30 months after FPI)

Secondary Outcomes (10)

• Overall survival (OS)

  at 18 months after last patient randomized

• Progression free survival (PFS)

  at study end (approx. 18 months after last patient randomized)

• Objective response rate (ORR)

  at study end (approx. 18 months after last patient randomized)

• Duration of response

  at study end (approx. 18 months after last patient randomized)

• Treatment exposure

  at study end (approx. 18 months after last patient randomized)

Study Arms (1)

Experimental

EXPERIMENTAL

Cabozantinib peroral 60 mg/day A stepwise dose de-escalation schedule on individual level is available for patients with lower tolerability against cabozantinib. The study treatment will be limited to a maximum of 12 months (including interruptions).

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

Cabozantinib 60 mg/day peroral

Experimental

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.
• 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.
• Patients who have shown progressive disease during or after first line therapy OR patients must have had their treatment interrupted due to the level of toxicities AND cabozantinib therapy is intended as second line therapy.
• 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.
• For women of childbearing potential and men who are sexually active with women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods.

You may not qualify if:

• Unwillingness to give informed consent for participation in the study.
• Prior sorafenib treatment.
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 5 months after last dose of study treatment.
• Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.
• Significant portal hypertension (moderate or severe ascites).
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• Liver cirrhosis Child-Pugh B with \> 7 points and Child-Pugh C.
• Severely impaired kidney function.
• History of encephalopathy in past 12 months, if not completely regressive or more than one episode within the last 6 months.
• Significant cardiovascular disease (such as New York Heart Association 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.
• Elevations of AST/ALT exceeding 5 X ULN.

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• Ipsen: collaborator

Study Sites (10)

Helios Klinikum Bad Saarow

Bad Saarow, 15526, Germany

Location

Universitätsklinikum Köln

Cologne, 50937, Germany

Location

Universitätsklinikum Halle (Saale)

Halle, 06120, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitätsklinikum Schleswig-Holstein

Kiel, 24105, Germany

Location

VK&K Studien

Landshut, 84036, Germany

Location

Universitätsklinikum Schleswig-Holstein

Lübeck, 23538, Germany

Location

Klinikum rechts der Isar der Technischen Universität München

München, 81675, Germany

Location

Johanna Etienne Krankenhaus

Neuss, 41462, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, 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

• Arndt Vogel, Prof. Dr.

  Hannover Medical School

  PRINCIPAL INVESTIGATOR

• Salah-Eddin Al-Batran, Prof. Dr.

  Institut für Klinische Krebsforschung IKF GmbH

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: August 4, 2020
• First Posted: August 13, 2020
• Study Start: December 8, 2020
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: January 30, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (10)