Trial record 8 of 85 for:    regorafenib

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2015 by SCRI Development Innovations, LLC
Sponsor:
Collaborator:
Sirtex Medical
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT02195011
First received: July 17, 2014
Last updated: January 19, 2015
Last verified: January 2015
  Purpose

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.


Condition Intervention Phase
Colorectal Neoplasms
Device: SIR-Spheres
Drug: Regorafenib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Number of participants with serious and non-serious adverse events [ Time Frame: up to 15 months ] [ Designated as safety issue: Yes ]
    Evaluate the safety of the two treatment cohorts combining regorafenib and SIR-Spheres in patients with metastatic colorectal cancer.


Secondary Outcome Measures:
  • Overall Response Rate (ORR) [ Time Frame: At 6 and 12 weeks after SIR-Spheres, and every 8 weeks thereafter, up to 18 months ] [ Designated as safety issue: No ]
    Proportion of patients with observed complete response (CR) or partial response (PR) according to RECIST 1.1 criteria.

  • Progression Free Survival (PFS) [ Time Frame: At 6 and 12 weeks after SIR-Spheres, and every 8 weeks thereafter, up to 18 months. ] [ Designated as safety issue: No ]
    Time to progression will be evaluated from Day 1 of study drug administration to disease progression as defined by RECIST 1.1 criteria, or death on study.

  • Overall Survival (OS) [ Time Frame: up to 18 months ] [ Designated as safety issue: No ]
    Overall survival will be evaluated from Day 1 of study drug administration to death.


Estimated Enrollment: 50
Study Start Date: June 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1: Regorafenib/SIR-Spheres/Regorafenib

Cohort 1: Regorafenib (one cycle) followed by SIR-Spheres followed by re-initiation of regorafenib 2-4 weeks after SIR-Spheres.

Twenty-five patients will be treated in Cohort 1. 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 administration of SIR-Spheres.

Device: SIR-Spheres
Radioembolization will be administered once by injection through a trans-femoral catheter into the hepatic artery.
Other Name: 90Y-Microspheres
Drug: Regorafenib
All patients will take regorafenib 160mg orally once daily on Days 1-21 of each 28-day cycle.
Other Name: Stivarga
Experimental: Cohort 2: SIR-Spheres/Regorafenib

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

Twenty-five patients will be treated in Cohort 2. 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
Radioembolization will be administered once by injection through a trans-femoral catheter into the hepatic artery.
Other Name: 90Y-Microspheres
Drug: Regorafenib
All patients will take regorafenib 160mg orally once daily on Days 1-21 of each 28-day cycle.
Other Name: Stivarga

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 rate (ORR), progression-free survival (PFS), and overall survival (OS).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 kidney 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02195011

Contacts
Contact: Sarah Cannon Research Institute 1-877-691-7274 asksarah@scresearch.net

Locations
United States, Missouri
Research Medical Center Recruiting
Kansas City, Missouri, United States, 64132
United States, Tennessee
Tennessee Oncology PLLC Recruiting
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
SCRI Development Innovations, LLC
Sirtex Medical
Investigators
Study Chair: Andrew Kennedy, MD SCRI Development Innovations, LLC
Study Chair: Johanna Bendell, MD SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT02195011     History of Changes
Other Study ID Numbers: SCRI GI 189
Study First Received: July 17, 2014
Last Updated: January 19, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Regorafenib
90Y
Radioembolization
SIR-Spheres Microspheres
Metastatic Colorectal Cancer
Liver Metastases
SIRT
Refractory

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases

ClinicalTrials.gov processed this record on April 16, 2015