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

NCT02195011 | Completed Phase 2 Results FDA Drug FDA Device

• 1 other identifier: SCRI GI 189
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Colorectal Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  up to 15 months

Secondary Outcomes (3)

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

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

• Median Progression-Free Survival

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

• Median Overall Survival

  up to 18 months

Study Arms (2)

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.

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.

Device: SIR-Spheres; Drug: Regorafenib

Interventions

SIR-Spheres DEVICE

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

Also known as: 90Y-Microspheres

Cohort 1: Regorafenib/SIR-Spheres/Regorafenib; Cohort 2: SIR-Spheres/Regorafenib

Regorafenib DRUG

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

Also known as: Stivarga

Cohort 1: Regorafenib/SIR-Spheres/Regorafenib; Cohort 2: SIR-Spheres/Regorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Sirtex Medical: collaborator

Study Sites (3)

Florida Cancer Specialists - North

St. Petersburg, Florida, 33705, United States

Location

Research Medical Center

Kansas City, Missouri, 64132, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: Senior Director, Regulatory Science
• Organization: Sarah Cannon Development Innovations

CANN.InnovationsMedical@sarahcannon.com

844-710-6157

Study Officials

• Andrew Kennedy, MD

  SCRI Development Innovations, LLC

  STUDY CHAIR

• Johanna Bendell, MD

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2014
• First Posted: July 21, 2014
• Study Start: July 1, 2014
• Primary Completion: June 4, 2017
• Study Completion: June 4, 2017
• Last Updated: December 5, 2023
• Results First Posted: July 12, 2018

Record last verified: 2018-07

Locations

US (3)