Neoplasms

Digestive System Diseases

All Conditions

Symptoms and General Pathology

Colorectal Neoplasms

Neoplasm Metastasis

Liver Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Hematinics

All Drugs and Chemicals

Liver Extracts

SIR-Spheres Y-90 resin microspheres are permanent implant and for single use only

Resin microspheres containing yttrium-90 (Y-90)

Hui Wen, B.S.

xixi Hu, MS

hongming Pan, PhD

weidong Han, PhD

This real-world study tries to collect data reflecting routine use of SIR-Spheres in patients diagnosed with unresectable liver metastases from Metastatic Liver Tumors From Primary Colorectal Cancer (mCRC) refractory to or intolerant to chemotherapy, in order to assess clinical response in a real-world setting and further validate the safe and appropriate use of SIR-Spheres in China.

This is a post-market trial evaluating the efficacy and safety of SIR-Spheres® Y-90 resin microspheres for the treatment of unresectable metastatic liver tumors from primary colorectal cancer. Patients enrolled should already complete the infusion of SIR-Spheres® and data are about to be collected both retrospectively and prospectively. 200 patients are anticipated to be enrolled and followed up for up to 24 months.

Observational Study for SIR-Spheres Therapy for the Treatment of Unresectable Metastatic Liver Tumors From Primary Colorectal Cancer

Percentage of subjects with complete or partial responses to the liver as determined by the investigator according to liver-specific RECIST 1.1 criteria

From the day of treatment with yttrium \[90Y\] resin microspheres to the time of death due to any cause

The percentage of subjects treated with yttrium \[90Y\] resin microspheres who survived at 1 year.

Defined as the time from the date of treatment with the yttrium \[90Y\] resin microspheres to the time when disease progression or subject death from any cause during the study period was first determined by the investigator according to RECIST 1.1 criteria, whichever occurred first.

Defined as the time from the date of treatment with yttrium \[90Y\] resin microspheres until the first time progression of liver disease or death of the subject from any cause during the study period was determined by the investigator according to liver-specific RECIST 1.1 criteria, whichever occurred first.

Defined as the percentage of subjects with complete or partial tumor response as determined by the investigator according to RECIST 1.1 criteria

Defined as the time from the first documented objective response to tumor recurrence or death from any cause during the study period as determined by the investigator according to RECIST 1.1 criteria, whichever occurs first

Defined as the time from the first documented liver objective remission to liver recurrence or death from any cause during the study period as determined by the investigator according to liver-specific RECIST 1.1 criteria, whichever occurs first

GrandPharma (China) Co., Ltd.

Neoplastic Processes

Regorafenib (one cycle) followed by SIR-Spheres followed by re-initiation of regorafenib 2-4 weeks after SIR-Spheres.

Patients will take regorafenib 160 mg orally once daily on Days 1-21 of each 28-day treatment cycle. SIR-Spheres microspheres will then be administered to the patient by injection through a trans-femoral catheter into the hepatic artery. Treatment with regorafenib will be re-started 2-4 weeks after SIR-Spheres administration.

SIR-Spheres followed by regorafenib to start 2-4 weeks after SIR-Spheres.

SIR-Spheres microspheres will be administered to the patient by injection through a trans-femoral catheter into the hepatic artery. After SIR-Spheres microspheres have been administered, the treatment with regorafenib will be initiated 2-4 weeks after administration of SIR-Spheres. Patients will take regorafenib 160 mg orally once daily on Days 1-21 of each 28-day treatment cycle.

Radioembolization will be administered once by injection through a trans-femoral catheter into the hepatic artery.

SIR-Spheres

All patients will take regorafenib 160mg orally once daily on Days 1-21 of each 28-day cycle.

Regorafenib

Andrew Kennedy, MD

Johanna Bendell, MD

The purpose of this study is to determine the safety of regorafenib, an antiangiogenic drug, when combined with radioembolization using SIR-Spheres® microspheres in the treatment of colorectal cancer (CRC) that has spread to the liver.

Recent targeted therapies and treatment strategies have shown promise in colorectal cancer; however, elimination of disease remains a challenge once spread to the liver. Radioembolization using SIR-Spheres® microspheres (SIR-Spheres) to treat liver-only or liver-dominant metastatic colorectal cancer (mCRC) has been successful in this refractory setting. In this open-label study we will compare the safety of two treatment cohorts in which radioembolization will be administered using the device SIR-Spheres microspheres (90Y resin microspheres) in combination with regorafenib to patients with mCRC with liver metastases. The two treatment cohorts will be evaluated for safety, overall response (OR), progression-free survival (PFS), and overall survival (OS).

Safety Study of Regorafenib and SIR-Spheres® Microspheres Radioembolization in Patients With Refractory Metastatic Colorectal Cancer With Liver Metastases

A Two Arm Safety Study of Regorafenib Before or After SIR-Spheres Microspheres (90Y) for the Treatment of Patients With Refractory Metastatic Colorectal Cancer With Liver Metastases

A treatment-related adverse event or serious adverse event was any untoward medical occurrence in a participant which was considered to have a relationship with the study drug (suspected to be possibly or probably related to the study drug per the Investigator's assessment). Adverse events and serious adverse events will be assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V4.03.

Defined as the number of patients with objective evidence of complete or partial response (CR or PR) using RECIST v 1.1. A CR is the complete disappearance of all target lesions. A PR is a decrease in of 30% or more of the diameter(s) of all target lesions from the baseline sum of diameters.

Defined as the time (in months) from date of randomization to the date of first observation of progression based on radiological assessment by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1, or date of death from any cause, in the absence of progressive disease (PD) or censored at the date of last adequate tumor assessment. Progressive Disease is defined by RECIST v1.1 as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest (nadir) sum while on study (this includes the baseline sum if that is the smallest on study), or the appearance of one or more new lesions.

Defined as the time (in months) from date of randomization to date of death from any cause, or censored at the date last known alive.

Sirtex Medical

SCRI Development Innovations, LLC

All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Patients with metastatic colorectal cancer (mCRC) with liver metastases received one cycle (28 days) of regorafenib followed by SIR-Spheres followed by re-initiation of regorafenib 2-4 weeks after SIR-Spheres.

Patients in Cohort 1 took 160 mg regorafenib orally once daily on Days 1-21 of each 28-day treatment cycle. SIR-Spheres microspheres were then be administered to patients by injection via trans-femoral catheter into the hepatic artery. Following treatment with SIR-Spheres, patients took 160 mg regorafenib orally once daily on Days 1-21 of each 28-day treatment cycle

Cohort 1: Regorafenib/SIR-Spheres/Regorafenib

Patients with metastatic colorectal cancer (mCRC) with liver metastases received SIR-Spheres microspheres followed by regorafenib to start 2-4 weeks after SIR-Spheres.

Patients in Cohort 2 received SIR-Spheres microspheres administered by injection via trans-femoral catheter into the hepatic artery. Following treatment with SIR-Spheres, patients took 160 mg regorafenib orally once daily on Days 1-21 of each 28-day treatment cycle

Cohort 2: SIR-Spheres/Regorafenib

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

All patients who received at least one dose of treatment.

Senior Director, Regulatory Science

All patients who receive at least one dose of treatment.

The Number of Participants With Treatment-Related Adverse Events and Serious Adverse Events as a Measure of Safety

Includes all patients who have received study treatment.

Number of Patients With an Objective Response (CR or PR)

Includes all patients who received treatment.

Median Progression-Free Survival

Median Overall Survival

Overall Study

Liver Diseases

Anti-Infective Agents

Trifluridine

Combination therapy with Tas-102 and radioembolization using 90Y resin microspheres

Oral nucleoside antitumor agent consisting of α,α,α-trifluorothymidine (FTD) and 5-chloro-6-(2-iminopyrrolidin-1-yl) methyl-2,4 (1H,3H)-pyrimidinedione hydro chloride (TPI) at a molar ratio of 1:0.5.

Tas-102

20-60mm resin microspheres containing Yttrium-90 (90Y, Y90) radioisotope

SIR-Sphere

Nicholas Fidelman, MD

Katherine Van Loon, MD

This is a phase I dose escalation study (3+3 design) with a dose expansion arm (12 patients) designed to evaluate safety of the combination of Tas-102 and radioembolization using Yttrium-90 (90Y) resin microspheres for patients with chemotherapy-refractory liver-dominant chemotherapy-refractory metastatic colorectal cancer (mCRC).

Randomized studies have demonstrated that Tas-102 has single agent activity against chemotherapy refractory colorectal cancer. A recent pre-clinical study has shown that Tas-102 may have activity as a radiation sensitizer in bladder cancer cell lines. Benefit of single agent Tas-102 against chemotherapy refractory colon cancer and the drug's promise a radiosensitizer make Tas-102 a potential candidate drug for testing in combination with radioembolization using Yttrium-90 resin microspheres in patients with liver-dominant chemotherapy-refractory mCRC. This is a phase I dose escalation study with a dose expansion arm designed to evaluate safety of the combination of Tas-102 and radioembolization using 90Y resin microspheres for patients with chemotherapy-refractory colon or rectal adenocarcinoma metastatic to the liver.

Tas-102 and Radioembolization With 90Y Resin Microspheres for Chemo-refractory Colorectal Liver Metastases

Phase I Study of Tas-102 and Radioembolization With 90Y Resin Microspheres for Chemo-refractory Colorectal Liver Metastases

Any adverse events grade ≥ 3 will be reviewed by the treating interventional radiologist and medical oncologist within 24 hours of being informed event. If none of the 3 patients in a cohort experiences a DLT, another 3 patients will be treated at the next higher dose level. However, if 1 of the first 3 patients experiences a DLT, 3 more patients will be treated at the same dose level. The dose escalation will continue until at least 2 patients among a cohort of 3-6 patients experience DLTs (i.e., ≥ 33% of patients with a dose-limiting toxicity at that dose level) or until 3-6 patients had been treated at TAS-102 dose of 35mg/m2 per day in 2 divided doses (up to a maximum of 80 mg per dose) administered concurrently with radioembolization cycles 1 and 2 without experiencing a DLT. DLT window will be 56 days (cycle 1, day 1 to cycle 2, day 28). Dose limiting toxicity will be reached when one of the clinical and/or laboratory parameters are met

Traditional 3+3 design will be used to determine the recommended dose for the dose expansion phase will be defined as the dose level just below this toxic dose level.

Radiographic overall response rate (measured in accordance to Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1) using imaging. Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): 30% decrease in the sum of the longest diameter of target lesionsStable Disease (SD): Small changes that do not meet the criteria for CR, PR, or Progressive Disease (PD): 20% increase in the sum of the longest diameter of target lesions. ORR will be defined as a ratio of the number of patients who demonstrated complete response (CR) or partial response (PR) to the number of all evaluated patients.

PFS will be defined as a time period that started at enrollment, during which a patient neither progressed nor died based on radiographic response.

HPFS will be defined as a time period that started at enrollment, during which a patient neither progressed in the liver nor died based on radiographic response.

EHPFS will be defined as a time period that started at enrollment, during which a patient neither progressed outside the liver nor died based on radiographic response

Overall Survival will be analyzed 12 months after the last patient is enrolled. Overall survival will be assessed using a two-sided, log-rank test. The survival function will be estimated using the Kaplan-Meier product limit method. In addition, two-sided 95% confidence intervals for the median overall survival will be computed

Proportion of patients with carcinoembryonic antigen (CEA) response with ≥ 50% decline from baseline (in patients with baseline level ≥ 3.2) post combination therapy with Tas-102 and 90Y radioembolization. Maximum percent change will be calculated. CEA level will only be followed for participants with elevated level (≥3.2) at baseline.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Observational Study for SIR-Spheres Therapy for the Treatment of Unresectable Metastatic Liver Tumors From Primary Colorectal Cancer	NCT06079242	Colorectal Neop...	Resin microsphe...	18 Years -	GrandPharma (China) Co., Ltd.
Safety Study of Regorafenib and SIR-Spheres® Microspheres Radioembolization in Patients With Refractory Metastatic Colorectal Cancer With Liver Metastases	NCT02195011	Colorectal Neop...	SIR-Spheres Regorafenib	18 Years -	SCRI Development Innovations, LLC
Tas-102 and Radioembolization With 90Y Resin Microspheres for Chemo-refractory Colorectal Liver Metastases	NCT02602327	Colon Cancer Rectal Cancer Liver Metastase...	Tas-102 SIR-Sphere	18 Years -	University of California, San Francisco
Observational Study for SIR-Spheres Therapy for the Treatment of Unresectable Metastatic Liver Tumors From Primary Colorectal Cancer	NCT06079242	Colorectal Neop...	Resin microsphe...	18 Years -	GrandPharma (China) Co., Ltd.

Spots Global Cancer Trial Database for 90y

Every month we try and update this database with for 90y cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for 90y

Every month we try and update this database with for 90y cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for 90y cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.