The purpose of this study is to determine the effect of a sunitinib administration schedule 2/1 (2 weeks of treatment followed by 1 week without) compared to a schedule 4/2 (4 weeks of treatment followed by 2 weeks without) on cardiopulmonary function in subjects with renal cell carcinoma. Subjects will be randomized 1:1 to one of two arms: 4/2 schedule of sunitinib administration or 2/1 schedule of sunitinib administration. Cardiopulmonary function will be assessed at baseline, week 4 (4/2 schedule only), week 5 (2/1 schedule only) and week 12. The investigators hypothesize that schedule 2/1 of sunitinib is not only better tolerated but will be associated with less fatigue and functional cardiovascular/muscular toxicity than the 4/2 schedule.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
7
Patients randomized to sunitinib schedule 4/2 will receive sunitinib at 50 mg daily for 4 weeks on, followed by 2 weeks off, per standard of care. Cardiopulmonary Exercise Testing (CPET) will be performed at baseline, 4 weeks and 12 weeks.
Patients randomized to sunitinib schedule 2/1 will receive sunitinib 50 mg daily for 2 weeks on, followed by 1 week off. Cardiopulmonary Exercise Testing (CPET) will be performed at baseline, 5 weeks and 12 weeks.
Duke Cancer Institute
Durham, North Carolina, United States
Change in Relative VO2 Peak From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules
Exercise Capacity will be assessed using Cardiopulmonary Exercise Testing (CPET) to determine VO2peak. Higher VO2 peak measured in mg/ml/min indicates better cardiac function. Mean change in cardiac functions will be assessed by the difference in Relative Peak VO2 from baseline to 12 weeks in both the arms.
Time frame: Baseline, week 12
Change in Difference Between Rest Left Ventricular Ejection Fraction (LVEF) and Cardiac Function by 2-D Echocardiography (2DE) From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules
Mean change in cardiac functions will be assessed by the difference in LVEF measured by 2D-Echo from baseline to 12 weeks in both the arms. Higher LVEF measured in percentage indicates better cardiac function.
Time frame: Baseline, week 12
Change in Difference Between Rest and Stress Left Ventricular Ejection Fraction (LVEF) and Cardiac Function by 3-D Echocardiography (3DE) From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules [Time Frame: Baseline, Week 12]
Time frame: Baseline, week 12
Change in One Repetition Maximum (1RM) in Upper and Lower Extremity Muscular Strength From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules
Mean change in upper and lower extremity maximal muscular strength as measured by the voluntary one-repetition max (1-RM) between week 12 and baseline. A 1-RM is defined as the greatest resistance that can be moved through the full range of motion in a controlled manner. This assessment included following exercises: leg press, chest press, and row. The heaviest weight lifted while adhering to the strict technique and form will be used to score the assessment.
Time frame: Baseline, week 12
Change in Muscular Endurance in Upper and Lower Extremity Muscular Strength From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules
Mean change in upper and lower extremity maximal muscular strength as measured by the muscular endurance which is 70% of 1-RM between week 12 and baseline. Muscular Endurance of the upper and lower body will be assessed as the number of repetitions to fatigue at 70% of the 1-RM. The same exercises and methods will be used as in the 1-RM determination.
Time frame: Baseline, week 12
Change in Muscle Cross-sectional Area (CSA) of the Major Muscles Near Lumbar3 (CT Scans and Slice-O-Matic® Software) From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules [Time Frame: Baseline, Week 12]
Time frame: Baseline, week 12
Change in Time Taken to Complete the 5-repititionChair-stand Test From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules
The 5-repetition Chair-Stand Test measures the time taken to complete 5 repetitions of the sit-to-stand maneuver performed on a chair. Standardized instructions are: "By the count of 3, please stand up and sit down as quickly as possible for 5 times. Place your hands on your lap, and do not use them throughout the procedure. Lean your back against the chair's backrest at the end of every repetition." Note: Timing will start when the subject's back left the backrest and will be stopped once the back touched the backrest.
Time frame: Baseline, week 12
Change in Time Taken to Complete the Timed up and Go Test From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules
Timed Up and Go (TUG) test assesses a person's mobility. TUG measures the time that a person takes to rise from a chair, walk three meters, turn around, walk back to the chair, and sit down. Scores of 10 seconds or less indicate normal mobility, 11 - 20 seconds are within normal limits for frail, elderly, and disabled subjects, and greater than 20 seconds suggests that further examination is required.
Time frame: Baseline, week 12
Change in Distance Walked During the 6 Minute Walk Test From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules
Subjects will be instructed to cover the longest distance possible in 6 minutes under the supervision of an exercise physiologist or trained designee. The walked distance will be determined in a measured corridor between 2 cones that were placed 30 meters apart
Time frame: Baseline, week 12
Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale Score From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules
Mean change in PRO: FACIT-Fatigue (FACIT-F, range 0 to 52) aggregate score between week 12 and baseline. Higher scores indicate better quality of life.
Time frame: Baseline, week 12
Change in Functional Assessment of Cancer Therapy - Kidney Symptom Index - 19 (FKSI-19) Score From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules
Mean change in PRO: FKSI- 19 (FKSI-19 Range 0 to 76) aggregate score between week 12 and baseline. Higher scores indicate better quality of life.
Time frame: Baseline, week 12
Change in Hospital Anxiety and Depression Survey (HADS) Score From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules
Mean change in PRO: HADS (HADS, range 0 to 21) aggregate score between week 12 and baseline. The HADS score has 2- subscales: Depression and Anxiety. Each sub-scale ranges from 0, 21. Higher scores indicate higher levels of depression and anxiety.
Time frame: Baseline, week 12
Change in Leisure Activity Score From the Godin-Leisure Questionnaire From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules
Mean change in PRO: Godin-Leisure questionnaire aggregate score between week 12 and baseline. This represents the activity level of a participant. There are no standard reference range for this assessment. Higher scores indicate higher physical activity.
Time frame: Baseline, week 12
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