A Phase 4 Study of Regorafenib in Metastatic Colorectal Cancer - Does Educating Physicians Change Patient Outcomes?
Condition: Physician Education
MeSH terms: Colorectal Neoplasms
Intervention: Regorafenib (Stivarga, BAY73-4506); iPAD application; Bayer specialist
Intervention description: Dose(s) 160 mg tablet (4 tablets per day at 40 mg) daily for 3 weeks on / 1 week off; Investigators were supported with enhanced drug-specific information via an iPad application (SMART).; The treating investigator will have access to the prescribing information and have ability to consult a Bayer specialist, should questions arise.
Phase: Phase 4
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Randomized trial to evaluate impact of healthcare provider( clinician and nursing staff)
      support and education on treatment discontinuation rates in the absence of progression in
      patients with metastatic colorectal cancer treated with regorafenib. Intensified education
      and support will be provided through an application for iPad which has automatic links to
      grading, dose reduction and side effect management ,as well as, references for additional
      articles.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically-proven metastatic CRC for which the decision of
             treatment with regorafenib was made

          -  Previous treatment with fluoropyrimidine-, oxaliplatin- and irinotecan-based
             chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy

          -  Male or female patients ≥ 18 years of age

          -  Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1

          -  Signed informed consent obtained before any study specific procedure is
             performed.Patients must be able to understand and willing to sign the written ICF.

          -  Life expectancy of at least 12 weeks

          -  Adequate bone marrow, liver and renal function as assessed by the following laboratory
             requirements:

               1. Total bilirubin ≤ 1.5 x the upper limits of normal (ULN)

               2. Alanine aminotransferase (ALT) and aspartate aminotransferease (AST)

                  ≤ 3.0 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer)

               3. Alkaline phosphastase limit ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver
                  involvement of their cancer)

               4. Lipase ≤ 1.5 x the ULN

               5. Amylase ≤ 1.5 x the ULN

               6. Serum creatinine ≤ 1.5 x the ULN

               7. International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time
                  (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless
                  receiving treatment with therapeutic anticoagulation. Patients being treated with
                  anticoagulant (e.g., heparin), will be allowed to participate provided no prior
                  evidence of an underlying abnormality in these parameters exists. Close
                  monitoring of at least weekly evaluations will be performed until INR and PTT are
                  stable based on a pre-dose measurement as defined by the local standard of care.

               8. Platelet count ≥ 100000 /mm3, hemoglobin (Hb) ≥ 9 g/dL, absolute neutrophil count
                  (ANC) ≥ 1500/mm3. Blood transfusion to meet the inclusion criteria will not be
                  allowed.

          -  Estimated creatinine clearance (CLcr) ≥ 30 mL/min as calculated using the
             Cockroft-Gault (C-G) equation.

          -  Women of childbearing potential must have a blood or urine pregnancy test performed a
             maximum of 7 days before start of study treatment, and a negative result must be
             documented before start of study treatment.

          -  Women of childbearing potential and men must agree to use adequate contraception
             before entering the program until at least 8 weeks after the last study drug
             administration.

        Exclusion Criteria:

          -  Unable to swallow oral medications.

          -  Prior use of regorafenib

          -  Previous assignment to treatment during this study. Patients permanently withdrawn
             from study participation will not be allowed to re-enter study.

          -  Uncontrolled hypertension (systolic blood pressure > 140 millimeters of mercury (mmHg)
             or diastolic pressure > 90 mmHg despite optimal medical management)

          -  Active or clinically significant cardiac disease including:

               1. Congestive heart failure - New York Heart Association (NYHA) > Class II

               2. Active coronary artery disease

               3. Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or
                  digoxin

               4. Unstable angina (anginal symptoms at rest), new-onset angina within 3 months
                  before randomization, or myocardial infarction within 6 months before
                  randomization

          -  Evidence or history of bleeding diathesis or coagulopathy, irrespective of severity

          -  Any hemorrhage or bleeding event > National Cancer Institute Common Terminology
             Criteria for Adverse Events (NCI-CTCAE) Grade 3 within 4 weeks prior to the start of
             study medication

          -  Arterial or venous thrombotic or embolic events such as cerebrovascular accident
             (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism
             within 6 month before the start of study medication (except for adequately treated
             catheter-related venous thrombosis occurring more than one month before the start of
             study medication)

          -  Previously untreated or concurrent cancer that is distinct in primary site or
             histology from colorectal cancer except cervical cancer in-situ, treated basal cell
             carcinoma, or superficial bladder tumor. Patients surviving a cancer that was
             curatively treated and without evidence of disease for more than 3 years before
             randomization are allowed.All cancer treatments must be completed at least 3 years
             prior to study entry (i.e.,signature date of the ICF).