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

NCT ID: NCT02195011

Last Updated: 2023-12-05

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-07-31

Study Completion Date

2017-06-04

Brief Summary

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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

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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

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Colorectal Neoplasms

Keywords

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Regorafenib 90Y Radioembolization SIR-Spheres Microspheres Metastatic Colorectal Cancer Liver Metastases SIRT Refractory

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1: Regorafenib/SIR-Spheres/Regorafenib

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.

Group Type EXPERIMENTAL

SIR-Spheres

Intervention Type DEVICE

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

Regorafenib

Intervention Type DRUG

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

Cohort 2: SIR-Spheres/Regorafenib

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.

Group Type EXPERIMENTAL

SIR-Spheres

Intervention Type DEVICE

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

Regorafenib

Intervention Type DRUG

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

Interventions

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SIR-Spheres

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

Intervention Type DEVICE

Regorafenib

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

Intervention Type DRUG

Other Intervention Names

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90Y-Microspheres Stivarga

Eligibility Criteria

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Inclusion Criteria

1. Histologically confirmed metastatic adenocarcinoma of the colon or rectum.
2. Patients who have been previously treated with or are not candidates for fluorouracil, oxaliplatin, irinotecan, and if Kras wild-type, anti EGFR therapy.
3. Considered an appropriate candidate for regorafenib therapy.
4. Measurable disease or evaluable disease as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
5. 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.
6. ECOG Performance Status score of 0-1.
7. Adequate hematologic, renal and liver function.
8. 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.
9. Life expectancy ≥ 3 months.
10. Ability to understand the nature of this study and give written informed consent

Exclusion Criteria

1. Most recent chemotherapy ≤14 days and ≥Grade 1 chemotherapy-related side effects, with the exception of alopecia.
2. 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.
3. 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.
4. Previous radiation delivered to the upper abdomen.
5. Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement.
6. 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.
7. Leptomeningeal metastases or spinal cord compression due to disease.
8. Pregnant or lactating.
9. Evidence of ascites, cirrhosis, portal hypertension, or thrombosis as determined by clinical or radiologic assessment.
10. History of abdominal fistula or gastrointestinal perforation ≤6 months prior to beginning study treatment.
11. Serious non-healing wound, active ulcer, or untreated bone fracture.
12. 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).
13. 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
14. 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).
15. 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.
16. Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis C.
17. 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.
18. Use of strong CYP34A inducers or inhibitors.
19. 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.
20. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
21. Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sirtex Medical

INDUSTRY

Sponsor Role collaborator

SCRI Development Innovations, LLC

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Andrew Kennedy, MD

Role: STUDY_CHAIR

SCRI Development Innovations, LLC

Johanna Bendell, MD

Role: STUDY_CHAIR

SCRI Development Innovations, LLC

Locations

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Florida Cancer Specialists - North

St. Petersburg, Florida, United States

Site Status

Research Medical Center

Kansas City, Missouri, United States

Site Status

Tennessee Oncology PLLC

Nashville, Tennessee, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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SCRI GI 189

Identifier Type: -

Identifier Source: org_study_id