Colorectal NeoplasmsPhase 2NCT02195011
Safety Study of Regorafenib and SIR-Spheres® Microspheres Radioembolization in Patients With Refractory Metastatic Colorectal Cancer With Liver Metastases
A Phase 2 study testing SIR-Spheres and Regorafenib in people with Colorectal Neoplasms, run by SCRI Development Innovations, LLC at 3 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasms
- What is being tested?
- SIR-Spheres and Regorafenib
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 3 sitesUnited States
- Study dates
- Jul 2014to 4 Jun 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed metastatic adenocarcinoma of the colon or rectum.
- Patients who have been previously treated with or are not candidates for fluorouracil, oxaliplatin, irinotecan, and if Kras wild-type, anti EGFR therapy.
- Considered an appropriate candidate for regorafenib therapy.
- Measurable disease or evaluable disease as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
- Measurable computed tomography (CT) scan evidence of liver metastases which are not treatable by surgical resection or local ablation with curative intent at the time of study entry.
- ECOG Performance Status score of 0-1.
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- Adequate hematologic, renal and liver function.
- Male patients with female partners of childbearing potential and women female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 30 days following last dose.
- Life expectancy ≥ 3 months.
- Ability to understand the nature of this study and give written informed consent
Who cannot join
- Most recent chemotherapy ≤14 days and ≥Grade 1 chemotherapy-related side effects, with the exception of alopecia.
- Use of a study drug ≤21 days or 5 half-lives (whichever is shorter) prior to initiation of study treatment. For study drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the study drug and administration of study treatment is required.
- Wide field radiotherapy (including therapeutic radioisotopes such as strontium-89 administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy.
- Previous radiation delivered to the upper abdomen.
- Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement.
- Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 2 weeks previously and there is no evidence of central nervous system disease progression, mild neurologic symptoms, and no requirement for chronic corticosteroid therapy.
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- Leptomeningeal metastases or spinal cord compression due to disease.
- Pregnant or lactating.
- Evidence of ascites, cirrhosis, portal hypertension, or thrombosis as determined by clinical or radiologic assessment.
- History of abdominal fistula or gastrointestinal perforation ≤6 months prior to beginning study treatment.
- Serious non-healing wound, active ulcer, or untreated bone fracture.
- Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥2, and malabsorption syndrome).
- Any of the following cardiac diseases currently or within the last 6 months:
- Unstable angina pectoris
- Congestive heart failure (NYHA ≥ Grade 2)
- Conduction abnormality not controlled with pacemaker or medication
- Significant ventricular or supraventricular arrhythmias (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible)
- Valvular disease with significant compromise in cardiac function
- Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] >180 mmHg or diastolic blood pressure (DBP) >100 mmHg) (patients with values above these levels must have their blood pressure (BP) controlled with medication prior to starting treatment).
- Serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
- Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis C.
- Presence of other active cancers, or history of treatment for invasive cancer ≤5 years. Patients with Stage I cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
- Use of strong CYP34A inducers or inhibitors.
- The herbal medications St. John's wort, kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng will not be allowed during study treatment. Patients should stop using these herbal medications 7 days prior to first dose of study drug.
- Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
- Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Research Medical Center
Kansas City, Missouri, 64132
Tennessee Oncology PLLC
Nashville, Tennessee, 37203
Florida Cancer Specialists - North
St. Petersburg, Florida, 33705
About this study
Official title: 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
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.
Read the detailed description
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).
- Conditions
- Colorectal Neoplasms
- Being tested
- SIR-Spheres, Regorafenib
- Keywords
- Regorafenib, 90Y, Radioembolization, SIR-Spheres Microspheres, Metastatic Colorectal Cancer, Liver Metastases, SIRT, Refractory
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SIR-SpheresDevice
Also called 90Y-Microspheres
Radioembolization will be administered once by injection through a trans-femoral catheter into the hepatic artery.
RegorafenibDrug
Also called Stivarga
All patients will take regorafenib 160mg orally once daily on Days 1-21 of each 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Regorafenib/SIR-Spheres/Regorafenib | Experimental | 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. Receives: Device: SIR-Spheres; Drug: Regorafenib |
| Cohort 2: SIR-Spheres/Regorafenib | Experimental | 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. Receives: Device: SIR-Spheres; Drug: Regorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Participants With Treatment-Related Adverse Events and Serious Adverse Events as a Measure of Safety
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.
Measured: up to 15 months
Secondary outcomes (3)
Number of Patients With an Objective Response (CR or PR)
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.
Measured: At 6 and 12 weeks after SIR-Spheres, and every 8 weeks thereafter, up to 18 months
Median Progression-Free Survival
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.
Measured: At 6 and 12 weeks after SIR-Spheres, and every 8 weeks thereafter, up to 18 months.
Median Overall Survival
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.
Measured: up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2014 (estimated)
- Study startJul 2014
- Primary completion4 Jun 2017
- Study completion4 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Sirtex Medical
- Responsible party
- Sponsor
- Investigators
- Andrew Kennedy, MD, Study chair, SCRI Development Innovations, LLCJohanna Bendell, MD, Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02195011
- Sponsor's protocol ID
- SCRI GI 189
- Status last verified
- Jul 2018
- First submitted
- 17 Jul 2014
- Last updated
- 5 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02195011
- Acronym / sponsor ID
- SCRI GI 189
- Conditions
- Colorectal Neoplasms
- Keywords
- Regorafenib, 90Y, Radioembolization, SIR-Spheres Microspheres, Metastatic Colorectal Cancer, Liver Metastases, SIRT, Refractory
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Sirtex Medical
- Study start
- Jul 2014 (actual)
- Primary completion
- 4 Jun 2017 (actual)
- Study completion
- 4 Jun 2017 (actual)
- First posted
- 21 Jul 2014 (estimated)
- Results
- Posted 12 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Regorafenib/SIR-Spheres/Regorafenib | Experimental | Device: SIR-Spheres, Drug: RegorafenibRegorafenib (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. |
| Cohort 2: SIR-Spheres/Regorafenib | Experimental | Device: SIR-Spheres, Drug: RegorafenibSIR-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histologically confirmed metastatic adenocarcinoma of the colon or rectum.
- Patients who have been previously treated with or are not candidates for fluorouracil, oxaliplatin, irinotecan, and if Kras wild-type, anti EGFR therapy.
- Considered an appropriate candidate for regorafenib therapy.
- Measurable disease or evaluable disease as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
- Measurable computed tomography (CT) scan evidence of liver metastases which are not treatable by surgical resection or local ablation with curative intent at the time of study entry.
Key exclusion criteria (26 listed)
- Most recent chemotherapy ≤14 days and ≥Grade 1 chemotherapy-related side effects, with the exception of alopecia.
- Use of a study drug ≤21 days or 5 half-lives (whichever is shorter) prior to initiation of study treatment. For study drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the study drug and administration of study treatment is required.
- Wide field radiotherapy (including therapeutic radioisotopes such as strontium-89 administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy.
- Previous radiation delivered to the upper abdomen.
- Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SIR-SpheresAlso: 90Y-MicrospheresRadioembolization will be administered once by injection through a trans-femoral catheter into the hepatic artery. | Device | Cohort 1: Regorafenib/SIR-Spheres/Regorafenib, Cohort 2: SIR-Spheres/Regorafenib |
| RegorafenibAlso: StivargaAll patients will take regorafenib 160mg orally once daily on Days 1-21 of each 28-day cycle. | Drug | Cohort 1: Regorafenib/SIR-Spheres/Regorafenib, Cohort 2: SIR-Spheres/Regorafenib |
Primary outcome
The Number of Participants With Treatment-Related Adverse Events and Serious Adverse Events as a Measure of Safety
Time frame: up to 15 months
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.
3 secondary outcomes
Number of Patients With an Objective Response (CR or PR)
Time frame: At 6 and 12 weeks after SIR-Spheres, and every 8 weeks thereafter, up to 18 months
Median Progression-Free Survival
Time frame: At 6 and 12 weeks after SIR-Spheres, and every 8 weeks thereafter, up to 18 months.
Median Overall Survival
Time frame: up to 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew Kennedy, MD study chair
SCRI Development Innovations, LLC
Johanna Bendell, MD study chair
SCRI Development Innovations, LLC
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SIR-Spheres and Regorafenib in people with Colorectal Neoplasms, run by SCRI Development Innovations, LLC at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Number of Participants With Treatment-Related Adverse Events and Serious Adverse Events as a Measure of Safety (time frame: up to 15 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2023.