Selective Internal Radiation Therapy (SIRT) Using SIR-Spheres® Y-90 Resin Microspheres on DoR & ORR in Unresectable Hepatocellular Carcinoma Patients

Unresectable Hepatocellular Carcinoma Clinical Trial

— DOORwaY90  

Official title:

A Prospective, Multicenter, Open-label Single Arm Study Evaluating the Safety & Efficacy of Selective Internal Radiation Therapy Using SIR-Spheres® Y-90 Resin Microspheres on DoR & ORR in Unresectable Hepatocellular Carcinoma Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04736121
• Other study ID #: STX2001
• Status: Recruiting
• Phase: N/A
• Start date: May 28, 2021
• Est. completion date: June 2025

Study information

• Verified date: March 2024
• Source: Sirtex Medical
• Contact: Janet Bell
• Phone: 781-721-3840
• Email: jbell[@]sirtex.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this pivotal study is to evaluate the safety and effectiveness of SIRT using SIR-Spheres Y-90 resin microspheres as first-line treatment for local control of HCC in patients with Barcelona Clinic Liver Cancer (BCLC) stage A, B1, B2, and C. SIR-Spheres consist of biocompatible resin microspheres containing yttrium-90 (Y-90), with a size between 20 and 60 microns in diameter. Y-90 is a high-energy pure beta-emitting isotope with no primary gamma emission. SIR-Spheres are indicated for the local tumor control of unresectable hepatocellular carcinoma (HCC) in patients with Barcelona Clinic Liver Cancer (BCLC) stage A, B1 and B2, maximal single lesion size of 8 cm, no macrovascular invasion, well-compensated liver function and good performance status. It is also indicated for the treatment of unresectable metastatic liver tumors from primary colorectal cancer with adjuvant intra-hepatic artery chemotherapy (IHAC) of Floxuridine (FUDR).

Description:

The investigation is a pivotal, prospective, multicenter, open-label single arm study evaluating treatment with hepatic arterial injection of SIR-Spheres. Up to 100 subjects will be treated (up to 150 consented) at up to 30 clinical sites in the United States. The population for this study includes patients diagnosed with HCC BCLC stage A, B1, B2, and C with maximal single lesion size of ≤ 8cm and who are not considered suitable for treatment by resection or eligible for ablation at time of study entry.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Willing, able, and mentally competent to provide written informed consent

2. Age 18 or older at the time of consent

3. All tumors must be measurable by CT or MRI according to localized mRECIST

4. Life expectancy = 6 months (to allow for adequate completion of study procedures and collection of data)

5. Diagnosis of HCC with Liver Imaging Reporting and Data System (LIRADS) 4 or 5 or by histology

6. Treatment-naïve patients or patients who have developed a new lesion following one of

these prior locoregional treatments:

1. Liver resection with negative pathologic margins, no microvascular invasion, and no recurrence at resection margins for at least 6 months post-treatment and no new lesions within 6 months of liver resection

2. Ablation of a single =3cm lesion with no recurrence of the treated lesion for at least 6 months post-treatment

7. BCLC stage A, B1, B2, and C with maximal single tumor size of =8 cm and sum of the maximal tumor dimensions of =12 cm with the entire tumor burden expected to be treatable within the perfused volume

8. At least one lesion =1 cm in diameter (long axis) measured according to mRECIST criteria by CT or MRI

9. Child-Pugh score of A5 or A6 at baseline

10. Eastern Cooperative Oncology Group (ECOG) performance score of =1 at baseline

11. Adequate blood count, liver enzymes, and renal function at baseline

1. Platelet count >50,000/microliter (patients may not receive a platelet transfusion or growth factors to increase the platelet count so that the patient may be eligible for the study)

2. White Blood Cell (WBC) = 3 x 10^9/L

3. Hemoglobin > 8.5 g/dL

4. Aspartate transaminase (AST) & Alanine transaminase (ALT) < 5 x upper limit normal

5. Bilirubin = 2.0 mg/dL

6. Albumin > 3.0 g/dL

7. International normalized ratio (INR) = 2.0

8. Glomerular filtration rate (GFR) > 50

12. Negative serum pregnancy test at baseline

13. Life expectancy of > 3 months without any active treatment

Exclusion Criteria:

1. Patients eligible for ablation or resection for their malignancy, in the opinion of the investigator, at the time of screening

2. Prior systemic anti-cancer therapy (including immunotherapy and/or targeted therapy), radiotherapy or use of other investigational agents for the treatment of HCC

3. Intrahepatic arteriovenous shunting (arteriovenous shunting resulting from a biopsy is allowed but must be embolized during the pre-treatment mapping procedure)

4. Incompetent biliary duct system, prior biliary intervention or a compromised Ampulla of Vater

5. Planned localized cancer treatment to the liver, other than the study treatment, throughout the duration of the study.

6. Planned systemic cancer treatment throughout the duration of the study

7. Patients with portal vein thrombosis

8. Patients with extrahepatic disease

9. Patients with contraindications to angiography and selective visceral catheterization

10. Evidence of extrahepatic collateral supply to the tumor

11. Evidence of potential delivery of mean radiation dose > 30 Gy to the lungs (single treatment)

12. Evidence of any detectable 99m Tc-macroaggregated albumin (99m Tc-MAA) flow outside of the liver in the abdomen, after application of established angiographic techniques to stop or mitigate such flow (e.g., placing catheter distal to gastric vessels or coiling)

13. Evidence that < 33% of the total liver volume is disease-free and will be spared SIR-Spheres treatment

14. Prior liver resection and/or liver transplant, with exception for patients with prior resection who meet inclusion criterion 6a

15. Female patients who are pregnant, breastfeeding, or premenopausal and unwilling to use an effective method of contraception through the 1-year follow-up; males unwilling to use effective method of contraception for 30 days post-procedure

16. Medical history of clotting disorders

17. Underlying pulmonary disease requiring chronic oxygen therapy

18. Evidence of portal hypertension with ascites as seen on cross-sectional imaging or any history of prior variceal bleeding within 6 months prior to screening

19. Concurrently enrolled in another study unless it is an observational, noninterventional study

20. Active infection (hepatitis B (HBV) infection with ongoing HBV treatment and successfully treated hepatitis C infection are allowed)

21. History of other cancer with current active treatment

22. Patients with drug or alcohol dependency (within 6 months prior to study entry) in the opinion of the investigator

23. History of severe allergy or intolerance to contrast agents, narcotics, or sedatives

24. Any condition that, in the opinion of the investigator, would interfere with safe delivery of the study treatment or with the interpretation of study results

Related Conditions & MeSH terms

• BCLC Stage A Hepatocellular Carcinoma
• BCLC Stage B Hepatocellular Carcinoma
• BCLC Stage C Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular
• Unresectable Hepatocellular Carcinoma

Intervention

Device:
• Resin microspheres containing yttrium-90 (Y-90)
Biocompatible resin microspheres are an injectable permanent implant and preferentially placed into the distal microvascular supply of tumors to provide direct irradiation of tissue and destruction of the microvascular bed. Spheres contain yttrium-90 (Y-90) and are a size between 20 and 60 microns in diameter.

Locations

Country	Name	City	State
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The University of Vermont Medical Center	Burlington	Vermont
United States	University of North Carolina - Chapel Hill Medical Center	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Cincinnati Cancer Center CTO	Cincinnati	Ohio
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Clinical Research Institute and Methodist Hospital	Dallas	Texas
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	UT MD Anderson Cancer Center	Houston	Texas
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of California Los Angeles - Ronald Reagan Medical Center	Los Angeles	California
United States	Miami Cardiac and Vascular Institute at Baptist Hospital	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Providence Holy Cross Medical Center	Mission Hills	California
United States	Columbia University CUIMC/NYPH	New York	New York
United States	Providence St. Joseph Hospital	Orange	California
United States	University of California Irvine	Orange	California
United States	Hospital of the University Pennsylvania	Philadelphia	Pennsylvania
United States	Allegheny-Singer Research Institute	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Sarasota Memorial Health Care System	Sarasota	Florida
United States	Inland Imaging	Spokane	Washington
United States	Stanford University	Stanford	California
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Sirtex Medical	Bright Research Partners

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	ORR uses a localized version of modified Response Evaluation Criteria in Solid Tumors ("localized mRECIST") criteria and best response through 9 months, in patients treated with SIR-Spheres Y-90 resin microspheres.	9 months
Primary	Duration of Response (DoR)	The interval from first time of response (complete response (CR) or partial response (PR)) until disease progression (PD) as defined by localized mRECIST criteria.	12 months
Secondary	Grade = 3 toxicity (CTCAE v5.0)	The severity of the adverse event should be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.	2 months and 6 months
Secondary	Incidence of liver resection	Liver resection as noted on follow-up case report form.	Post-procedure follow-up: 1, 2, 4, 6, 9, 12, 24 months
Secondary	Incidence of liver transplant	Liver transplant as noted on follow-up case report form.	Post-procedure follow-up: 1, 2, 4, 6, 9, 12, 24 months
Secondary	Quality of life metrics - FACT-Hep Questionnaire	Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire	Pre-procedure, 2, 4, 6, 9, and 12 months
Secondary	Quality of life metrics - EQ-5D-5L Questionnaire	EuroQol 5 Dimension 5 Level (EQ-5D-5L) questionnaire	Pre-procedure, 2, 4, 6, 9, and 12 months