A Phase 4 Study of Regorafenib in Metastatic Colorectal Cancer - Does Educating Physicians Change Patient Outcomes? (SMART)

Does Physician Education Influence Side Effect Management and Does it Increase Time on Treatment in the Absence of Progression ? A Phase 4 Open-label Trial With Regorafenib in Metastatic Colorectal Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Physician Education
• Intervention / Treatment: Drug: Regorafenib (Stivarga, BAY73-4506); Other: iPAD application; Other: Bayer specialist

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
  • California
    • Anaheim, California, United States, 92801
    • Orange, California, United States, 92668
  • Florida
    • Lake City, Florida, United States, 32024
  • Illinois
    • Skokie, Illinois, United States, 60076
    • Skokie, Illinois, United States, 60077
  • Indiana
    • Lafayette, Indiana, United States, 47905
  • Maryland
    • Columbia, Maryland, United States, 21044
  • North Carolina
    • Fayetteville, North Carolina, United States, 28304
  • Ohio
    • Canton, Ohio, United States, 44718
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74146
  • Pennsylvania
    • Gettysburg, Pennsylvania, United States, 17325
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
  • Texas
    • Houston, Texas, United States, 77024
    • Tyler, Texas, United States, 75701
  • Virginia
    • Bristol, Virginia, United States, 24201
    • Portsmouth, Virginia, United States, 23704

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SMART; Investigators were supported with enhanced drug-specific information via an iPad application (SMART).	Drug: Regorafenib (Stivarga, BAY73-4506); Dose(s) 160 mg tablet (4 tablets per day at 40 mg) daily for 3 weeks on / 1 week off; Other: iPAD application; Investigators were supported with enhanced drug-specific information via an iPad application (SMART).
Active Comparator: Standard of Care; Investigators were supported with standard prescribing information.	Drug: Regorafenib (Stivarga, BAY73-4506); Dose(s) 160 mg tablet (4 tablets per day at 40 mg) daily for 3 weeks on / 1 week off; Other: Bayer specialist; The treating investigator will have access to the prescribing information and have ability to consult a Bayer specialist, should questions arise.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of Patients Who Discontinue Prior to Documented Progression of Disease (PD) or Death	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Treatment		Up to 1 year
Dose Intensity as Percentage of Planned Dose	Dose level 0 (standard starting dose) @ 160mg po qd. Dose level - 1 @ 120 mg po qd. Dose level - 2 @ 80 mg po qd. This schedule reflects the FDA-approved dosing specified in the prescribing information.	Up to 1 year
Incidence of Grade 3 Hand-foot-skin Reaction (HFSR), Fatigue, Diarrhea, Hypertension	Documented during visits as part of the interval history. All AEs will be reported in the CRF with a diagnosis, start/stop dates, action taken.	Up to 1 year
Investigator Comfort With the Use of Regorafenib and Management of AEs as Measured by Questionnaire	Investigator comfort of managing adverse events, adjusting dosing schedule, and satisfaction with SMART application measured by a questionnaire; 10 categories were answered on a 1 - 7 scale.	Up to 1 year
Satisfaction of Investigator/Nurse With Enhanced Drug-specific Information Via SMART Questionnaire	Investigator comfort of managing adverse events, adjusting dosing schedule, and satisfaction with SMART application measured by a questionnaire; 10 categories were answered on a 1 - 7 scale.	Up to 1 year

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2014
• Primary Completion (Actual): February 26, 2016
• Study Completion (Actual): April 8, 2016

Study Registration Dates

• First Submitted: October 7, 2014
• First Submitted That Met QC Criteria: November 6, 2014
• First Posted (Estimate): November 10, 2014

Study Record Updates

• Last Update Posted (Actual): October 19, 2017
• Last Update Submitted That Met QC Criteria: October 16, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 17347

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No