1. time on treatment (TT) (Time Frame - start of treatment until end of treatment (max. 336 days)): Primary endpoint of the trial is the time on treatment (TT). TT is defined as one plus the last date of treatment with Cabozantinib minus the first date of treatment with Cabozantinib, and will be measured in days (note that Cabozantinib will be administered as a single dose per day). The end of treatment must be confirmed by the investigator. In particular, planned discontinuations or missing compliance will not be considered as end of treatment without confirmation.
Secondary outcome:
1. Overall survival (OS) (Time Frame - screening visit until date of death, maximum until the last registered patient reached the second follow-up (6 months after end of therapy)): Overall survival (OS), is the time to death of any cause. OS is measured in days, defined as death date minus registration date.
2. Progression-free survival (PFS) (Time Frame - screening visit until the time to tumor progression or date of death from any cause, whichever came first, maximum until the last registered patient reached the second follow-up (6 months after end of therapy)): Progression-free survival (PFS) is the time to tumor progression or death of any cause, whichever comes first. PFS is measured in days, defined as date of diagnosis of tumor progression by mRECIST criteria minus registration date. If a patient dies without previous diagnosis of tumor progression, date of diagnosis is replaced by death date.
3. Duration of response (DoR) (Time Frame - screening visit until the time from achievement of response or date of death from any cause, whichever came first, maximum until the last registered patient reached the second follow-up (6 months after end of therapy)): is the time from achievement of response (i.e., measurement criteria for CR or PR are first met, cf. Eisenhauer et al., 2009, p. 236) until the first date that tumor recurrence or progression is documented (taking as reference the smallest measurements recorded in the study) or death of any cause, whichever comes first. DoR is measured in days, defined as date of documentation of tumor progression by mRECIST criteria minus date of documentation of tumor response (CR or PR). If a patient dies without previous diagnosis of tumor progression, date of progression documentation is to be replaced by death date. If CR or PR will never be documented for a patient, DoR is set to "zero".
4. Response rates (Time Frame - screening visit until end of treatment (max. 336 days)): Response rates, measured in percent, are defined as the number of patients whose best tumor response observed by mRECIST criteria is CR, PR, SD or PD, respectively, divided by the total number of registered patients. The overall response rate (ORR) is defined as the number of patients whose best tumor response observed by mRECIST criteria is CR or PR divided by the total number of registered patients.
5. Median average dose (Time Frame - start of treatment until end of treatment (max. 336 days)): Median average dose, measured in milligram (mg). Averages of all Cabozantinib doses administered will be calculated weekly from first date of treatment until end of treatment. Discontinuations of treatment for any reason, including missing compliance, will be included into this calculation as zero doses. Median average dose is defined as the median of the obtained sequence of averages.
6. Image-based endpoint: Tumor progression (Time Frame - screening until end of treatment (max. 336 days)): Tumor progression, assessed at Visits 3, 6, 9, 12 and EoT visit (if applicable) in comparison to the state at Screening, by mRECIST criteria.
7. Image-based endpoint: Progression of tumoral macrovascular invasion (Time Frame - screening until end of treatment (max. 336 days)): Progression of tumoral macrovascular invasion of hepatic and/or portal vein branches, assessed at Visits 3, 6, 9, 12 and EoT visit (if applicable) according to the working instruction for radiologists, in comparison to state at Screening.
8. Image-based endpoint: Progression of extrahepatic HCC manifestations (Time Frame - screening until end of treatment (max. 336 days)): Progression of extrahepatic HCC manifestations, assessed at Visits 3, 6, 9, 12 and EoT visit (if applicable) according to the working instruction for radiologists, in comparison to state at Screening.
9. Image-based endpoint: Total tumor volume (Time Frame - screening until end of treatment (max. 336 days)): Total tumor volume (TTV), assessed at Screening, Visits 3, 6, 9, 12 and EoT visit (if applicable), measured in cm^3 according to the working instruction for radiologists.
10. Image-based endpoint: Affection rate (Time Frame - screening until end of treatment (max. 336 days)): Affection rate, assessed at Screening, Visits 3, 6, 9, 12 and EoT visit (if applicable), measured in percent. Affection rate is defined as total tumor volume divided by total liver volume, both measured in cm^3 according to the working instruction for radiologists.
11. Concentration of Alpha-fetoprotein (AFP), (Time Frame - screening until end of treatment (max. 336 days)): Concentration of Alpha-fetoprotein (AFP), measured in µg/l, at Screening and Visits 0, 3, 6, 9, 12 and EoT visit (if applicable).
12. Child-Pugh classification score (Time Frame - screening until first follow-up (one month after EoT)): Child-Pugh classification score, measured in levels from A to C, at Screening and Visits 3, 6, 9, 12, EoT and FU1 (if applicable).
13. ECOG Performance Status (Time Frame - screening until first follow-up (one month after EoT)): ECOG Performance Status, measured in levels from 0 to 5, at Screening and Visits 3, 6, 9, 12, EoT and FU1 (if applicable).
14. drug-related interruption, reduction or termination of treatment (safety endpoint) (Time Frame - start of treatment until end of treatment (max. 336 days)): Descriptive documentation
15. occurence of clinical symptoms of liver dysfunction (safety endpoint) (Time Frame - start of treatment until end of treatment (max. 336 days)): Descriptive documentation
Cabozantinib: The medication is taken once a day for 336 days (max.). The start dose is 60mg and can be reduced according to the physicians decision. 40mg and 20mg are also available.
Quelle: ClinicalTrials.gov
Sie können folgenden Inhalt einem Kollegen empfehlen:
"Cabozantinib Treatment in a Phase II Study for Patients With Hepatocellular Carcinoma (HCC) Refractory to PD-1 Inhibitors"
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