Yttrium-90 Carbon Microspheres in Patients With Unresectable Colorectal Liver Metastases (NRT-uCRLM)

Yttrium-90 Carbon Microspheres in Patients With Unresectable Colorectal Liver Metastases: A Multicentre, Prospective, Open-label, Single-arm Trial

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

Study Overview

• Status: Recruiting
• Conditions: Unresectable Colorectal Liver Metastases
• Intervention / Treatment: Combination product: Selective internal radiation therapy (SIRT) with yttrium-90 carbon microspheres

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Hai-Dong Zhu, MD; Phone Number: +862583262224; Email: zhuhaidong9509@163.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 100730
      • Recruiting
      • Zhongda Hospital Southeast University
      • Contact: Gaojun Teng, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Yttrium-90 carbon microspheres; Single dose of yttrium-90 carbon microspheres injection. Patients will be assessed by SPECT-CT imaging within 24 hours for yttrium-90 distribution in the chest and upper abdomen, including extrahepatic shunts, intrahepatic distribution, and target lesion distribution as expected.Ten Patients will be tested for the radioactivity of yttrium-90 in blood, urine, and feces (if available).

Combination product: Selective internal radiation therapy (SIRT) with yttrium-90 carbon microspheres; Yttrium-90 carbon microspheres SIRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival Rate of Liver Target Lesions	Survival probability of patients without imaging progression of liver target lesions	3 months after yttrium-90 injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Yttrium-90 distribution	Assessed by SPECT-CT imaging in the chest and upper abdomen, including extrahepatic shunts, intrahepatic distribution, and target lesion distribution as expected.Ten Patients will be tested for the radioactivity of yttrium-90 in blood, urine, and feces (if available)	Within 24 hours
Objective response rate (ORR)	Evaluated by the investigator and independent image review committee respectively (CTCAE 1.1)	Up to 24 months
Duration of response (DOR)	Time without imaging progression, evaluated by the investigator and independent image review committee respectively (CTCAE 1.1)	Up to 24 months
Hepatic progression-free survival (hPFS)	Time without imaging progression of liver target lesions, evaluated by the investigator and independent image review committee respectively (CTCAE 1.1)	Up to 24 months
Time to progression (TTP)	Time with tumor progression, evaluated by the investigator and independent image review committee respectively (CTCAE 1.1)	Up to 24 months
Progression-free survival (PFS)	Evaluated by the investigator and independent image review committee respectively (CTCAE 1.1)	Up to 24 months
Overall survival (OS)	Survival time	Up to 24 months
Disease control rate (DCR)	Probability of tumor control	Up to 24 months
Adverse events	Rate of adverse events	Up to 24 months

Collaborators and Investigators

• Sponsor: Zhongda Hospital
• Investigators: Principal Investigator: Gao-Jun Teng, MD, Zhongda Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2022
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: December 25, 2022
• First Submitted That Met QC Criteria: January 10, 2023
• First Posted (Actual): January 20, 2023

Study Record Updates

• Last Update Posted (Estimate): January 30, 2023
• Last Update Submitted That Met QC Criteria: January 26, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Neoplastic Processes; Neoplasm Metastasis; Liver Neoplasms
• Other Study ID Numbers: CHANCE2303-NRT6003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No