Colorectal liver metastases liver metastases from colon and rectal cancer
Conditions
Interventions
Injection of escalating doses of 90Y-microspheres followed by DEBIRI via a
catheter in the hepatic arteries.
Sponsors
Universitair Medisch Centrum Utrecht
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Written informed consent. 2. >=18 years old with confirmed unresectable liver metastases from CRC 3. The primary tumor should be clinically stable. 4. Bilobar (to avoid bias in toxicity analysis), unresectable liver dominant mCRC (i.e. up to 2 lesions limited to one extra-hepatic organ with a maximum size of 1 cm and 2 cm for lymph nodes), with disease progression after first line systemic treatment. 5. Eligible to receive second-line standard-of-care chemotherapy with an irinotecan-based chemotherapy regimen. 6. Measurable (target) liver lesions on contrast-enhanced CT, according to RECIST 1.1. 7. Contrast-enhanced CT and FDG-PET-CT maximum 4 weeks prior to enrolment. 8. Tumor replacement >= 5% and = 12 weeks. 12. Hematologic function: WBC >= 3.0 x 10^9/L, platelets >= 100 x 10^9/L, absolute neutrophil count ; 1.5 x 10^9/L, Hemoglobin; 5 mmol/L. 13. Adequate organ function as measured by: o GFR >= 35 ml/min. o Serum transaminases (AST; ALT) 3 g/dL.
Exclusion criteria
Exclusion criteria: 1. History of hepatic encephalopathy. 2. Contraindications to angiography. 3. Known severe allergy or intolerance to contrast agents, that cannot be managed medically. 4. Pulmonary insufficiency or clinically evident chronic obstructive pulmonary disease. 5. Cirrhosis or portal hypertension. 6. Prior liver-directed therapy (i.e. EBRT, chemoembolization, radioembolization, hepatic segmentectomies, radiofrequency ablation spanning >2 segments). 7. Treatment with VEGF inhibitors within 28 days prior to receiving 90Y glass microspheres. 8. Prior intervention for, or compromise of, the Ampulla of Vater. 9. Presence of clinically evident ascites (trace ascites on imaging is acceptable), or Child-Pugh score B/C. 10. Toxicities due to prior cancer therapy that have not resolved before the initiation of study treatment, if the investigator determines that the continuing complication will compromise the safe treatment of the patient. 11. Significant life-threatening extra-hepatic disease, including patients who have unresolved diarrhea or serious unresolved infections (e.g. patients who are known to be HIV positive or have acute HBV or HCV). 12. Contraindications to the planned second line standard-of-care chemotherapy regimen. 13. Pregnancy and/or breastfeeding. 14. Patients suffering from psychic disorders that make a comprehensive judgment impossible, such as psychosis, hallucinations and/or depression. 15. Patients who are declared incapacitated. 16. Participation in a clinical trial with an investigational therapy within 30 days prior to enrolment. 17. Any co-morbid disease or condition that would place the patient at undue risk. 18. Contraindications to TACE (e.g. porto-systemic shunt, portal vein thrombosis, hepatofugal blood flow, severe atherosclerosis precluding arterial access). 19. Contraindications to irinotecan (concomitant use with St John*s wort).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The maximum tolerated absorbed dose of 90Y-microspheres (TheraSphere®, BTG international) when combined with DEBIRI for liver dominant mCRC. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints: - Adverse events (AEs) and serious adverse events (SAEs), up to 2 months after the second and final treatment cycle. AEs and SAEs are defined by the study protocol (NCI Common Toxicity Criteria for Adverse Events; CTCAE v 5.0). - Overall response rate (ORR, every 3 months up to progression) of the CRLM from the first treatment cycle by RECIST v1.1 and PERCIST, according to index lesions, hepatic response and overall response. - Overall Survival (OS), evaluated 12 months after enrolment of the last patient. - Conversion from non-resectable to resectable CRLM. - Tumor marker (CEA) at 2 months after the second and final treatment cycle - Circulating tumor DNA levels before and after treatment. - Amount of drug-eluting beads (DEB) delivered. - Post-treatment dosimetry, related to pre-treatment dosimetry, as assessed by Simplict90Y* software. | — |
Countries
Netherlands
Outcome results
None listed