Safety Study of Regorafenib and SIR-Spheres® Microspheres Radioembolization in Patients With Refractory Metastatic Colorectal Cancer With Liver Metastases
Condition: Colorectal Neoplasms
MeSH terms: Colorectal Neoplasms; Neoplasm Metastasis
Intervention: SIR-Spheres; Regorafenib
Intervention description: Radioembolization will be administered once by injection through a trans-femoral catheter into the hepatic artery.; All patients will take regorafenib 160mg orally once daily on Days 1-21 of each 28-day cycle.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Regorafenib; 90Y; Radioembolization; SIR-Spheres Microspheres; Metastatic Colorectal Cancer; Liver Metastases; SIRT; Refractory

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.
    

Eligibility 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 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.