Clinical trial NCT05692037: Yttrium-90 Carbon Microspheres in Patients With Unresectable Colorectal Liver Metastases
Official title: Yttrium-90 Carbon Microspheres in Patients With Unresectable Colorectal Liver Metastases: A Multicentre, Prospective, Open-label, Single-arm Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Unresectable Colorectal Liver Metastases
Lead sponsor: Zhongda Hospital
Sponsor class: OTHER
First posted: 2023-01-20
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy and safety of yttrium-90 carbon microspheres in patients with unresectable colorectal liver metastases

Detailed description: The efficacy and safety of yttrium-90 carbon microspheres in patients with unresectable colorectal liver metastases remain unknown. This multicentre, prospective, open-label, single-arm trial is designed to evaluate the safety and efficacy of yttrium-90 carbon microspheres in patients with unresectable colorectal liver metastases. The primary endpoints are the progression-free survival rates of liver target lesions. While the secondary endpoints include the safety, tumor control, and the distribution characteristics of yttrium-90 carbon microspheres.

Eligibility criteria: Inclusion Criteria:

1. Eastern Cooperative Oncology Group performance status ≤ 1;
2. Expected survival time ≥ 3 months;
3. Confirmed liver metastasis of colorectal cancer;
4. Complete resection and no local recurrence of the primary colorectal cancer;
5. Intolerance, failure to the previous anti-tumor treatments or, or recurrence liver metastasis after surgical resection;
6. Without extrahepatic metastases, inoperable or refuse surgical resection;
7. At least one well defined tumor (RECIST 1.1);
8. Tumor burden ≤ 50% of the total liver volume;
9. Child-Pugh score ≤ 7;
10. Adequate organ function: ① Blood routine \[no blood transfusion or colony-stimulating factor (G-CSF) treatment within 14 days\]: absolute neutrophil count ≥ 1.5 × 109/L; platelet ≥ 75 × 109/L; hemoglobin ≥ 90 g/L; ② Liver function: total bilirubin ≤ 2 times upper limit of normal (ULN); alanine transaminase and aspartate aminotransferase ≤ 5. 0 ULN; alkaline phosphatase ≤ 2.5 ULN; Albumin \> 30 g/L; ③ Renal function: Cr ≤ 1.5 ULN; creatinine clearance ≥ 50 mL/min (calculated according to Cockcroft-Gault formula); ④ Coagulation function: international normalized ratio, prothrombin time and activated partial thromboplastin time were less than 1.5 ULN; ⑤ Cardiovascular function: left ventricular ejection fraction ≥ 50%;
11. According to CTCAE 5.0 standard, all adverse events of previous systematic anti-cancer treatment have recovered to baseline or ≤ 1 grade, \[except for the following: neuropathy induced by previous anti-cancer treatment is stable (≤ 2 grade) and hair loss\];
12. Women and men of childbearing age must agree to take strict and effective contraceptive measures during the study period and within 6 m after the end of the trial. Men are forbidden to donate sperm. The pregnancy test results of female patients of childbearing age during the screening period and within 24 hours before administration must be negative.

Exclusion Criteria:

1. With previous history of hepatic encephalopathy;
2. Severe pulmonary insufficiency (forced expiratory volume at one second / forced vital capacity \< 50% or forced expiratory volume at one second /predicting value \< 50% or maximum volume per minute \< 50 L/min);Obvious chronic obstructive pulmonary disease or interstitial pneumonia;
3. Percentage of hepatopulmonary shunt \> 10%, or the single lung radiation absorbed dose \> 30 Gy;
4. With hepatic artery malformation and unable to intubate hepatic artery;
5. Tumor thrombus in main portal vein;
6. Have received radiotherapy or transcatheter arterial chemoembolization (patients who have received transcatheter arterial non-iodized oil chemoembolization are judged by researchers);
7. The last anti-tumor treatment (surgery, chemotherapy, immunotherapy, targeted therapy) was less than 4 weeks before the drug administration;
8. Clinical manifestations of portal hypertension, moderate-severe or refractory ascites, or decompensated liver cirrhosis;
9. Major surgery or severe trauma within 28 days before yttrium-90 administration;
10. Participated in other trial within 1 month before yttrium-90 administration;
11. Pregnant and lactating women;
12. Serious infections in active stage or need systematic treatment;
13. With positive results of HIV antibody test;
14. The researchers judge that there is unresolved toxicity from previous treatment and will continue to exist, which may endanger the safety of patients;
15. The researcher judged clinical or laboratory examination abnormality or other reasons.

Primary outcomes:
measure: Progression Free Survival Rate of Liver Target Lesions
timeFrame: 3 months after yttrium-90 injection
Secondary outcomes:
measure: Adverse events
timeFrame: Up to 24 months
measure: Yttrium-90 distribution
timeFrame: Within 24 hours
measure: Objective response rate (ORR)
timeFrame: Up to 24 months
measure: Duration of response (DOR)
timeFrame: Up to 24 months
measure: Hepatic progression-free survival (hPFS)
timeFrame: Up to 24 months
measure: Time to progression (TTP)
timeFrame: Up to 24 months
measure: Progression-free survival (PFS)
timeFrame: Up to 24 months
measure: Overall survival (OS)
timeFrame: Up to 24 months
measure: Disease control rate (DCR)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
state: Jiangsu
Study officials:
affiliation: Zhongda Hospital
name: Gao-Jun Teng, MD
role: PRINCIPAL_INVESTIGATOR
References: