FTD-TPI, Bevacizumab, and Radioembolization With 166Ho-microspheres in Refractory Metastatic Colorectal Cancer
NCT Number: NCT06563986
Acronym: STARLIGHT
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Metastatic Colorectal Cancer
Interventions: DRUG: Systemic treatment (FTD-TPI and bevacizumab)|DEVICE: Radioembolization with 166-Ho microspheres
Sponsor: UMC Utrecht
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 40
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-06-18
Completion Date: 2028-06
Locations: UMC Utrecht, Utrecht, 3584CX, Netherlands

Summary:
Extrahepatic disease progression limits clinical efficacy of individualized radioembolization for patients with refractory metastatic colorectal cancer (mCRC). In the same patient population, trifluridine/tipiracil (FTD-TPI) and bevacizumab lead to disease control and overall survival benefit and may be a radiosensitizer.

The purpose of this study is to determine safety, tolerability, and activity of individualized radioembolization with 166Holmium (166Ho)-microspheres combined with FTD-TPI and bevacizumab.

Primary Outcome Measures: Hepatic objective response rate (hORR) (PERCIST 1.0), Hepatic objective response rate (hORR) will be assessed by Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0., Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.
Secondary Outcome Measures: Hepatic objective response rate (hORR) (RECIST 1.1), Hepatic objective response rate (hORR) will be assessed by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1., Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.|Overall and extra-hepatic ORR (RECIST 1.1), Overall and extra-hepatic ORR will be assessed by RECIST 1.1., Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.|Overall and extra-hepatic ORR (PERCIST 1.0), Overall and extra-hepatic ORR will be assessed by PERCIST 1.0., Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.|Serious adverse events (SAE's), The occurrence of any (suspected unexpected) serious adverse event (SAE) that is possibly, probably or definitely related to the combined treatment., Evaluated every 8 weeks after start treatment during the first half year. The collection period will start from the first day of the first treatment cycle until 180 days thereafter.|Grade ≥3 adverse events (CTCAE 5.0), The rate of grade ≥3 adverse events (CTCAE 5.0)., Evaluated every 8 weeks after start treatment during the first half year. The collection period will start from the first day of the first treatment cycle until 180 days thereafter.|Occurrence of radioembolization-induced liver disease (REILD), Radioembolization-induced liver disease (REILD) is defined as a total bilirubin increase to grade ≥3 or higher according to the CTCAE v5.0, in combination with ascites and low albumin, developing at least 2 weeks after radioembolization and up to 4 months after radioembolization, in the absence of tumor progression or biliary obstruction., Evaluated every 8 weeks after start treatment during the first half year.|Radioembolization related vascular events, Number of participants with a vascular event (dissection, pseudo-aneurism, thrombus etc.) that is possibly, probably or definitely related to the radioembolization., Evaluated every 8 weeks after start treatment during the first half year.|Dose reductions, dose delays of FTD-TPI, The frequency of dose reductions and dose delays of FTD-TPI during the first 2 cycles., Evaluated during the first two cycles (each cycle is 28 days).|Radioembolization completion rate, Defined as the successful treatment of both hemi-livers (in case of bilateral disease) according to the individualized treatment plan designed at the scout dose., Evaluated immediately after the radioembolization treatment.|Progression free survival (PFS), PFS is defined as time from the first day of the first treatment cycle to progression of disease or death, whichever occurs first. Progression of disease is based on tumor response as observed on radiographic imaging according to RECIST 1.1., Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.|Overall survival (OS), OS is defined as the time from the first day of the first treatment cycle to the date of death. Patients still alive at the analysis cut-off date are censored at the last date known to be alive. OS will be collected for all patients from the Personal Records Database (BRP), yearly during the duration of the study., Evaluated once per year until the end of the study (the end of study is defined as six months after the first day of the first treatment cycle (each cycle is 28 days) of the 36th evaluable participant).
Other Outcome Measures: Dosimetry scout + post treatment 1 and 2, To evaluate biodistribution / dosimetry using CT and quantitative SPECT both for scout dose imaging and post-treatment imaging. Tumor dose and normal liver dose will be calculated for each hemi-liver in the scout procedure and two post treatment scans., Evaluated immediately after the radioembolization treatment.