Single-arm, phase II trial of trifluridine/tipiracil (FTD-TPI), bevacizumab, and individualized radioembolization with 166Ho-microspheres in refractory metastatic colorectal cancer.

Phase 2

• Conditions: 10019818; colorectal cancer; liver metastases; 10017990; 10019815

• Registration Number: NL-OMON56792
• Lead Sponsor: niversitair Medisch Centrum Utrecht

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 18 June 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 40

Inclusion Criteria

• Unresectable liver dominant mCRC
• Prior therapy with fluoropyrimidine, oxaliplatin, and irinotecan for the
treatment of advanced colorectal cancer and had demonstrated progressive
disease or intolerance to their last regimen
• Written informed consent
• Age >=18 years
• Estimated hepatic tumor replacement >= 10% and <= 50% of total liver volume
• ECOG performance status 0-1
• Adequate organ function as measured by:
o WBC >= 3.0 x 109/L, platelets >= 100 x 109/L, absolute neutrophil count > 1.5 x
109/L, Hemoglobin > 5 mmol/L (>8.1 g/dL)
o eGFR >= 35 ml/min
o Serum transaminases (AST & ALT) <= 5 x ULN
o Total bilirubin <= ULN
o Albumin > 3 g/dL
• At least one measurable liver lesion according to the PERCIST 1.0
• Included in PLCRC

Exclusion Criteria

• Significant extrahepatic disease, defined as symptomatic extrahepatic
disease, greater than 10 pulmonary nodules (maximum diameter of each lung
metastasis <20mm), and/or peritoneal carcinomatosis. (Definition of liver
dominant disease)(Fidelman et al., 2022)
• Eligible for local treatment of liver metastases (e.g. surgical resection,
ablation)
• Lung shunt >20 Gy, as calculated using scout dose SPECT/CT
• Absorbed tumor dose <90 Gy when dosing at a maximum average absorbed normal
liver dose
• Other malignancy confounding prognosis
• Receipt of chemotherapy within 28*days prior to study treatment
• Previous or current treatment with radioembolization
• Major surgery within 28 days or incompletely healed surgical incision before
starting study therapy
• Any serious comorbidity preventing the safe administration of anti-VEGF
antibody treatment. This includes uncontrolled hypertension or treatment with
>=3 antihypertensive drugs, arterial (cerebro)vascular event within the past 6
months, history of severe bleeding, history of GI perforation, or presence of
fistulae
• Any serious and/or chronic liver disease preventing the safe administration
of radioembolization
• Uncorrectable extrahepatic deposition of scout dose activity; activity in the
falciform ligament, portal lymph nodes and gallbladder is accepted
• Pregnancy or breastfeeding
• Body weight over 150 kg (because of maximum table load)
• Known severe allergy for intravenous contrast fluids
• Participation to another investigational study which may compromise any
endpoint of the study

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To assess activity of radioembolization, FTD-TPI, and bevacizumab in terms of<br /><br>hepatic objective tumor response (hORR) determined by PERCIST 1.0</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Activity<br /><br>• Hepatic objective response rate (hORR) (RECIST 1.1)<br /><br>• Overall and extra-hepatic ORR (RECIST 1.1, PERCIST 1.0)<br /><br><br /><br>Safety<br /><br>• SAE*s<br /><br>• Grade >=3 adverse events (CTCAE 5.0)<br /><br>• Occurrence of REILD (see 8.1.2)<br /><br>• Radioembolization related vascular events<br /><br><br /><br>Tolerability<br /><br>• Dose reductions, dose delays of FTD-TPI<br /><br>• Radioembolization completion rate<br /><br><br /><br>Efficacy<br /><br>• Progression-free survival<br /><br>• Overall survival</p><br>