The CaPture trial is a prospective, multi-centre, non-randomized phase II study. Its aim is to assess feasibility, safety and efficacy signals of Cabozantinib treatment in patients with HCC and prior non-response or disease progression during a PD-1 or PD-L1 inhibitor treatment. Since the potential study population is very small, the sample size has been fixed in advance to N = 40. Time on treatment (TT) will be measured as primary endpoint.
Patients will be recruited at the participating trial sites (up to ten trial sites), which are all specialized in treatment of patients with HCC. Once potential patients are identified by trial physicians, they will be asked for trial participation and informed consent by one investigator of the CaPture trial. Patients included within 4 weeks after diagnosis of failure of preceding PD-1/PD-L1 inhibitory treatment. After baseline, visits are previewed on a 4weekly (28 days) basis during the whole duration of Cabozantinib study treatment, which can be used for a maximum of 12 months (336 days). The treatment with Cabozantinib will be performed in accordance with the valid license and according to the judgement of the treating physician.The tablet is taken once a day, starting normally with the highest dosage (60 mg). The doses 20mg and 40mg are still available and can be used for dose reduction. During the visits, the patient will be questioned for compliance and side effects and examined for clinical and laboratory parameters. Response to Cabozantinib should be assessed at least every 12 weeks (84 days) by either CT scan or MRI. After termination of Cabozantinib study treatment the first follow-up visit takes place one month after the end of therapy in person. Further follow-up visits can be done by phone to collect patient's status and further treatment. In addition to the time on treatment (TT), survival, response, feasibility, biomarkers, health status and safety should also be tested. Furthermore there is an concomitant scientific project. The aim of this project is to examinate the association of HCC related biomarkers with response to Cabozantinib in patients treated in the CaPture study. For this, we will analyse liver biopsy samples as well as circulating markers in patients who are willing to participate in the project.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
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.
Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus Medizinische Klinik und Poliklinik I
Dresden, Saxony, Germany
MVZ Mitte/MVZ Delitzsch GmbH
Leipzig, Saxony, Germany
University Hospital Leipzig
Leipzig, Saxony, Germany
Charite Universitätsmedizin, Campus Virchow Klinikum, Klinik für Hepatologie/Gastroenterologie
Berlin, Germany
time on treatment (TT)
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.
Time frame: start of treatment until end of treatment (max. 336 days)
Overall survival (OS)
Overall survival (OS), is the time to death of any cause. OS is measured in days, defined as death date minus registration date.
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)
Progression-free survival (PFS)
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.
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)
Duration of response (DoR)
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".
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
TREATMENT
Masking
NONE
Enrollment
16
Universitätsklinikum Mannheim
Mannheim, Germany
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)
Response rates
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.
Time frame: screening visit until end of treatment (max. 336 days)
Median average dose
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.
Time frame: start of treatment until end of treatment (max. 336 days)
Image-based endpoint: Tumor progression
Tumor progression, assessed at Visits 3, 6, 9, 12 and EoT visit (if applicable) in comparison to the state at Screening, by mRECIST criteria.
Time frame: screening until end of treatment (max. 336 days)
Image-based endpoint: Progression of tumoral macrovascular invasion
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.
Time frame: screening until end of treatment (max. 336 days)
Image-based endpoint: Progression of extrahepatic HCC manifestations
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.
Time frame: screening until end of treatment (max. 336 days)
Image-based endpoint: Total tumor volume
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.
Time frame: screening until end of treatment (max. 336 days)
Image-based endpoint: Affection rate
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.
Time frame: screening until end of treatment (max. 336 days)
Concentration of Alpha-fetoprotein (AFP),
Concentration of Alpha-fetoprotein (AFP), measured in µg/l, at Screening and Visits 0, 3, 6, 9, 12 and EoT visit (if applicable).
Time frame: screening until end of treatment (max. 336 days)
Child-Pugh classification score
Child-Pugh classification score, measured in levels from A to C, at Screening and Visits 3, 6, 9, 12, EoT and FU1 (if applicable).
Time frame: screening until first follow-up (one month after EoT)
ECOG Performance Status
ECOG Performance Status, measured in levels from 0 to 5, at Screening and Visits 3, 6, 9, 12, EoT and FU1 (if applicable).
Time frame: screening until first follow-up (one month after EoT)
drug-related interruption, reduction or termination of treatment (safety endpoint)
Descriptive documentation
Time frame: start of treatment until end of treatment (max. 336 days)
occurence of clinical symptoms of liver dysfunction (safety endpoint)
Descriptive documentation
Time frame: start of treatment until end of treatment (max. 336 days)