Trial Outcomes & Findings for Safety Study of Regorafenib and SIR-Spheres® Microspheres Radioembolization in Patients With Refractory Metastatic Colorectal Cancer With Liver Metastases (NCT NCT02195011)

NCT ID: NCT02195011

Last Updated: 2023-12-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

26 participants

Primary outcome timeframe

up to 15 months

Results posted on

2023-12-05

Participant Flow

Between July 2014 and February 2017, 26 patients with metastatic colorectal cancer (mCRC) with liver metastases were enrolled. The study was closed early due to slow enrollment.

Participant milestones

Participant milestones
Measure	Cohort 1: Regorafenib/SIR-Spheres/Regorafenib 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 2: 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
Overall Study STARTED	25	1
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	25	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: Regorafenib/SIR-Spheres/Regorafenib 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 2: 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
Overall Study Adverse Event	4	0
Overall Study Progressive Disease	18	1
Overall Study Withdrawal by Subject	3	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: Regorafenib/SIR-Spheres/Regorafenib n=25 Participants 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 2: SIR-Spheres/Regorafenib n=1 Participants 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	Total n=26 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants	1 Participants n=7 Participants	18 Participants n=5 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants	0 Participants n=7 Participants	8 Participants n=5 Participants
Age, Continuous	56 years n=5 Participants	64 years n=7 Participants	56 years n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	0 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	1 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants	1 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	25 Participants n=5 Participants	1 Participants n=7 Participants	26 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 15 months

Population: All patients who receive at least one dose of treatment.

Outcome measures

Outcome measures
Measure	Cohort 1: Regorafenib/SIR-Spheres/Regorafenib n=25 Participants 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 2: SIR-Spheres/Regorafenib n=1 Participants 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
The Number of Participants With Treatment-Related Adverse Events and Serious Adverse Events as a Measure of Safety	25 Participants	1 Participants

SECONDARY outcome

Timeframe: At 6 and 12 weeks after SIR-Spheres, and every 8 weeks thereafter, up to 18 months

Population: Includes all patients who have received study treatment.

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.

Outcome measures

Outcome measures
Measure	Cohort 1: Regorafenib/SIR-Spheres/Regorafenib n=25 Participants 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 2: SIR-Spheres/Regorafenib n=1 Participants 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
Number of Patients With an Objective Response (CR or PR)	1 Participants	0 Participants

SECONDARY outcome

Timeframe: At 6 and 12 weeks after SIR-Spheres, and every 8 weeks thereafter, up to 18 months.

Population: Includes all patients who received treatment.

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.

Outcome measures

Outcome measures
Measure	Cohort 1: Regorafenib/SIR-Spheres/Regorafenib n=25 Participants 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 2: SIR-Spheres/Regorafenib n=1 Participants 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
Median Progression-Free Survival	3.7 months Interval 2.6 to 9.7	NA months Not reached at this time

SECONDARY outcome

Timeframe: up to 18 months

Population: Includes all patients who received treatment.

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.

Outcome measures

Outcome measures
Measure	Cohort 1: Regorafenib/SIR-Spheres/Regorafenib n=25 Participants 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 2: SIR-Spheres/Regorafenib n=1 Participants 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
Median Overall Survival	12.1 Months Interval 6.0 to 16.4	NA Months Not reached at this time.

Adverse Events

Cohort 1: Regorafenib/SIR-Spheres/Regorafenib

Serious events: 10 serious events

Other events: 25 other events

Deaths: 16 deaths

Cohort 2: SIR-Spheres/Regorafenib

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1: Regorafenib/SIR-Spheres/Regorafenib n=25 participants at risk 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 2: SIR-Spheres/Regorafenib n=1 participants at risk 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
Gastrointestinal disorders Constipation	4.0% 1/25 • Up to 15 months. 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.	0.00% 0/1 • Up to 15 months. 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.
Hepatobiliary disorders Cholecystitis acute	4.0% 1/25 • Up to 15 months. 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.	0.00% 0/1 • Up to 15 months. 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.
Gastrointestinal disorders Abdominal pain	8.0% 2/25 • Up to 15 months. 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.	0.00% 0/1 • Up to 15 months. 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.
Metabolism and nutrition disorders Hyponatraemia	4.0% 1/25 • Up to 15 months. 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.	0.00% 0/1 • Up to 15 months. 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.
Vascular disorders Hypertensive crisis	4.0% 1/25 • Up to 15 months. 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.	0.00% 0/1 • Up to 15 months. 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.
Psychiatric disorders Mental status changes	4.0% 1/25 • Up to 15 months. 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.	0.00% 0/1 • Up to 15 months. 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.
Cardiac disorders Myocardial infarction	4.0% 1/25 • Up to 15 months. 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.	0.00% 0/1 • Up to 15 months. 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.
Infections and infestations Sepsis	8.0% 2/25 • Up to 15 months. 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.	0.00% 0/1 • Up to 15 months. 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.
Gastrointestinal disorders Diarrhoea	4.0% 1/25 • Up to 15 months. 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.	0.00% 0/1 • Up to 15 months. 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.
Musculoskeletal and connective tissue disorders Back pain	4.0% 1/25 • Up to 15 months. 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.	0.00% 0/1 • Up to 15 months. 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.
Reproductive system and breast disorders Pelvic pain	4.0% 1/25 • Up to 15 months. 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.	0.00% 0/1 • Up to 15 months. 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.
Musculoskeletal and connective tissue disorders Muscle haemorrhage	4.0% 1/25 • Up to 15 months. 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.	0.00% 0/1 • Up to 15 months. 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.
Gastrointestinal disorders Intestinal perforation	4.0% 1/25 • Up to 15 months. 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.	0.00% 0/1 • Up to 15 months. 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.
Hepatobiliary disorders Portal hypertension	4.0% 1/25 • Up to 15 months. 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.	0.00% 0/1 • Up to 15 months. 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.

Other adverse events

Additional Information

Senior Director, Regulatory Science

Sarah Cannon Development Innovations

Phone: 844-710-6157

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60