Physician Education
Conditions
Brief 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.
Interventions
DRUGRegorafenib (Stivarga, BAY73-4506)
Dose(s) 160 mg tablet (4 tablets per day at 40 mg) daily for 3 weeks on / 1 week off
OTHERiPAD application
Investigators were supported with enhanced drug-specific information via an iPad application (SMART).
OTHERBayer specialist
The treating investigator will have access to the prescribing information and have ability to consult a Bayer specialist, should questions arise.
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of Patients Who Discontinue Prior to Documented Progression of Disease (PD) or Death | Up to 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Treatment | Up to 1 year | — |
| Dose Intensity as Percentage of Planned Dose | Up to 1 year | 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. |
| Incidence of Grade 3 Hand-foot-skin Reaction (HFSR), Fatigue, Diarrhea, Hypertension | Up to 1 year | 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. |
| Investigator Comfort With the Use of Regorafenib and Management of AEs as Measured by Questionnaire | Up to 1 year | 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. |
| Satisfaction of Investigator/Nurse With Enhanced Drug-specific Information Via SMART Questionnaire | Up to 1 year | 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. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 10 study centers in United States, from 11 NOV 2014 (first subject first visit) to 26 FEB 2016 (last subject last visit).
Pre-assignment details
Of the 23 screen participants, 2 participants were screen fails, 2 consented but never started treatment due to early study termination and 19 patients entered treatment.
Participants by arm
| Arm | Count |
|---|---|
| SMART Participants received 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). | 12 |
| Standard of Care Participants received 160 mg tablet (4 tablets per day at 40 mg) daily for 3 weeks on / 1 week off. Investigators were supported with standard prescribing information. | 11 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 4 |
| Overall Study | Not treated | 2 | 0 |
| Overall Study | Progression of disease | 3 | 2 |
| Overall Study | Screening failed | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | SMART | Standard of Care | Total |
|---|---|---|---|
| Age, Continuous | 61.08 Years STANDARD_DEVIATION 15.28 | 59.91 Years STANDARD_DEVIATION 4.29 | 60.52 Years STANDARD_DEVIATION 11.7 |
| Sex: Female, Male Female | 6 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 6 Participants | 8 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 18 / 19 |
| serious Total, serious adverse events | 3 / 19 |
Outcome results
Primary
Proportion of Patients Who Discontinue Prior to Documented Progression of Disease (PD) or Death
Time frame: Up to 1 year
Population: The study was pre-maturely terminated. No data were collected from participants for this assessment.
Secondary
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.
Time frame: Up to 1 year
Population: The study was pre-maturely terminated. No data were collected from participants for this assessment.
Secondary
Duration of Treatment
Time frame: Up to 1 year
Population: The study was pre-maturely terminated. No data were collected from participants for this assessment.
Secondary
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.
Time frame: Up to 1 year
Population: The study was pre-maturely terminated. No data were collected from participants for this assessment.
Secondary
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.
Time frame: Up to 1 year
Population: The study was pre-maturely terminated. No data were collected from participants for this assessment.
Secondary
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.
Time frame: Up to 1 year
Population: The study was pre-maturely terminated. No data were collected from participants for this assessment.