JOURNAL ONKOLOGIE – STUDIE
A Phase II, Non-randomized, Single Arm, Translational Study of Cabozantinib for Patients With Hepatocellular Carcinoma (HCC) Refractory to Lenvatinib Treatment
Rekrutierend
NCT-Nummer:
NCT04511455
Studienbeginn:
Dezember 2020
Letztes Update:
24.12.2020
Wirkstoff:
Cabozantinib
Indikation (Clinical Trials):
Carcinoma, Carcinoma, Hepatocellular
Geschlecht:
Alle
Altersgruppe:
Erwachsene (18+)
Phase:
Phase 2
Sponsor:
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Collaborator:
Ipsen
Studienleiter
Principal Investigator
Hannover Medical School Department of Gastroenterology, Hepatology and Endocrinology
Kontakt
Kontakt:
Phone: +49 176
Phone (ext.): 1 532 9590
E-Mail: vogel.arndt@mh-hannover.de» Kontaktdaten anzeigen
Kontakt:
Phone: +49 69 7601
Phone (ext.): 4635
E-Mail: riedel.johanna@ikf-khnw.de» Kontaktdaten anzeigen
Studienlocations
(1 von 1)
23538 Lübeck
(Schleswig-Holstein)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Jens Marquardt, Prof.» Ansprechpartner anzeigen
Studien-Informationen
Detailed Description:This is a open-label, single-arm, multicenter phase II trial for patients with locally
advanced and/or metastatic and/or unresectable hepatocellular carcinoma (HCC).
Patients who have histologically proven or were clinically diagnosed (by guideline criteria
in cirrhotic patients) with locally advanced or metastatic and/or unresectable HCC will be
included to receive 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 temporary
interruptions).
Tumor tissue will be collected for accompanying research project. (Participation is optional
for participant).
During treatment, clinical visits (blood cell counts, ECG, detection of toxicity) occur every
four weeks during treatment phase. Safety will be monitored continuously by careful
monitoring of all adverse events (AEs) and serious adverse events (SAEs) reported.
During treatment, tumor response will be assessed by the Investigator according to RECIST 1.1
(radiological imaging by CT and/or MRI of the chest, abdomen, pelvis and all other sites of
disease every 10 weeks until end of treatment (EOT) and every 12 weeks during follow-up (FU),
in case of EOT due to other reasons than progressive disease. Safety-FU visit and Survival FU
visits will be assessed 30 days-, and every 12 weeks after EOT.
Ein-/Ausschlusskriterien
Inclusion Criteria:1. Fully-informed written consent.
2. 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.
3. Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by
histology/ cytology or clinically by guideline criteria in cirrhotic patients
4. Disease that is not amenable to curative surgical and/or locoregional therapies, or
progressive disease after surgical and /or locoregional therapies.
5. Patients who have shown progressive disease despite of lenvatinib treatment (in terms
of lenvatinib monotherapy or combination therapy with IO) OR patients must have had
their treatment interrupted after at least 1 administration, as treatment with
lenvatinib is no longer clinically indicated due to the level of toxicities.
6. ECOG performance status ≤ 2.
7. Resolution of any acute, clinically significant treatment-related toxicity from prior
therapy to Grade 1 prior to study entry, with the exception of alopecia.
8. 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.
Exclusion Criteria:
1. Unwillingness to give informed consent for participation in the study.
2. Prior sorafenib treatment.
3. Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment
or within at least 5 months after last dose of study treatment.
4. Women of childbearing potential must have a negative serum pregnancy test result
within 14 days prior to initiation of study treatment.
5. Significant portal hypertension (moderate or severe ascites).
6. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
7. Liver cirrhosis Child-Pugh B (> 7 points).
8. Severely impaired kidney function.
9. History of encephalopathy in past 12 months.
10. 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.
11. Baseline QTcF >500 ms.
12. 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.
13. 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.
14. 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.
15. Elevations of AST/ALT exceeding 5 X ULN.
16. Treatment with investigational systemic therapy within 28 days prior to initiation of
study treatment.
17. Prior cabozantinib use.
18. Is currently participating 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.
19. Patients who have been incarcerated or involuntarily institutionalized by court order
or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.
20. 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].
Studien-Rationale
Primary outcome:1. Time-on-treatment (Time Frame - at study end (approx. 30 months after FPI)):
Time on treatment will be assessed as time from date of first dose of cabozantinib intake till date of permanent discontinuation of treatment.
Secondary outcome:
1. Overall survival (OS) (Time Frame - at 18 months after last patient randomized):
Survival rates will be assessed from the date of first dose of cabozantinib intake to the date of death from any cause using Kaplan-Meier methods.
2. Progression free survival (PFS) (Time Frame - at study end (approx. 18 months after last patient randomized)):
Survival rates for the different time points will be determined using the Kaplan-Meier analysis and RECIST 1.1.
3. Objective response rate (ORR) (Time Frame - at study end (approx. 18 months after last patient randomized)):
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.
4. Duration of response (Time Frame - at study end (approx. 18 months after last patient randomized)):
Time from documentation of tumor response to disease progression.
5. Treatment exposure (Time Frame - at study end (approx. 18 months after last patient randomized)):
Time on treatment/dose intensity/dose reductions
6. Toxicity: o Treatment-related adverse events (TRAEs) o TRAE related treatment interruptions o TRAE related treatment modifications o TRAE related treatment discontinuations (Time Frame - at study end (approx. 18 months after last patient randomized)):
All observed toxicities 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.
7. Change in ECOG Performance Status (Time Frame - at study end (approx. 18 months after last patient randomized)):
Eastern Cooperative Oncology Group patient performance status (Grading from 0 to 5)
8. Change in ALBI Grade (Time Frame - at study end (approx. 18 months after last patient randomized)):
ALBI score = -0.085 × (albumin g/L) + 0.66 × l g(TBil μmol/L)
9. Change in Child Pugh Score (Time Frame - at study end (approx. 18 months after last patient randomized)):
Child-Pugh Classification Score (Grading from A to C)
10. Translational research (Time Frame - at study end (approx. 18 months after last patient randomized)):
Correlation of biomarkers potentially associated with clinical efficacy (OS, PFS and ORR) of cabozantinib by NGS Oncopanel analysis and VEGF module expression analysis.
Geprüfte Regime
- Cabozantinib:
Cabozantinib 60 mg/day peroral
Quelle: ClinicalTrials.gov
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