NCT03109015: ASSET

Alternative Schedule Sunitinib in Metastatic Renal Cell Carcinoma: Cardiopulmonary Exercise Testing

Completed Phase 2 Results posted Last updated 8 October 2024

What this trial tests

Phase 2 trial testing Sunitinib in Carcinoma, Renal Cell in 7 participants. Completed in 8 October 2019.

Timeline

27 September 2017

Primary endpoint
8 October 2019

8 October 2019

Quick facts

Lead sponsor	Duke University
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	7
Start date	27 September 2017
Primary completion	8 October 2019
Estimated completion	8 October 2019
Sites	1 location across United States

Drugs / interventions tested

• Sunitinib (sunitinib) — full drug profile →
• Sunitinib (sunitinib) — full drug profile →

Conditions studied

• Carcinoma, Renal Cell — all drugs for Carcinoma, Renal Cell →

Sponsor

Duke University

Who can join

18 and older, any sex, with Carcinoma, Renal Cell. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Relative VO2 Peak From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules Primary · Baseline, week 12

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.

Group	Value	95% CI
Schedule 4/2	-1.13	± 2
Schedule 2/1	1.27	± 1.9

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 Secondary · Baseline, week 12

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.

Group	Value	95% CI
Schedule 4/2	1.5	± 4.1
Schedule 2/1	-9.0	± 10.6

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 Secondary · Baseline, week 12

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.

Seated Row

Group	Value	95% CI
Schedule 4/2	7	± 20
Schedule 2/1	6.67	± 35.2

Chest Press

Group	Value	95% CI
Schedule 4/2	-6.5	± 12.7
Schedule 2/1	-6.0	± 18.5

Leg Press

Group	Value	95% CI
Schedule 4/2	52.25	± 83.1
Schedule 2/1	15	± 105

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 Secondary · Baseline, week 12

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.

Seated Row

Group	Value	95% CI
Schedule 4/2	1.25	± 7.5
Schedule 2/1	4.33	± 24.8

Chest Press

Group	Value	95% CI
Schedule 4/2	-4.5	± 8.9
Schedule 2/1	-4.0	± 12.5

Leg Press

Group	Value	95% CI
Schedule 4/2	36.5	± 58.9
Schedule 2/1	10.33	± 73.5

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 Secondary · Baseline, week 12

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.

Group	Value	95% CI
Schedule 4/2	-0.43	± 0.9
Schedule 2/1	-2.05	± 0.5

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 Secondary · Baseline, week 12

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.

Group	Value	95% CI
Schedule 4/2	-0.5	± 1.3
Schedule 2/1	0	± 1.7

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 Secondary · Baseline, week 12

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

Group	Value	95% CI
Schedule 4/2	1.43	± 13.3
Schedule 2/1	-69.2	± 83.1

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 Secondary · Baseline, week 12

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.

Group	Value	95% CI
Schedule 4/2	-2.89	± 3.8
Schedule 2/1	-2.87	± 5.2

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 Secondary · Baseline, week 12

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.

Group	Value	95% CI
Schedule 4/2	2.75	± 4.8
Schedule 2/1	-1.0	± 3.6

Change in Hospital Anxiety and Depression Survey (HADS) Score From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules Secondary · Baseline, week 12

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.

Change in Anxiety (HADS)

Group	Value	95% CI
Schedule 4/2	0.75	± 1.5
Schedule 2/1	0.3	± 1.1

Change in Depression (HADS)

Group	Value	95% CI
Schedule 4/2	0.0	± 2.4
Schedule 2/1	1.3	± 2.9

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 Secondary · Baseline, week 12

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.

Group	Value	95% CI
Schedule 4/2	1.67	± 17.6
Schedule 2/1	0.5	± 36.1

Adverse events — posted to ClinicalTrials.gov

Time frame: 12 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Schedule 4/2

Serious: 0/4 (0%)

Deaths: 0/4

Schedule 2/1

Serious: 2/3 (67%)

Deaths: 0/3

Serious adverse events (2 terms)

Reaction	System	Schedule 4/2	Schedule 2/1
Fatigue	General disorders	—	—
Hypotension	Vascular disorders	—	—

Other adverse events (29 terms — click to expand)

Reaction	System	Schedule 4/2	Schedule 2/1
Diarrhea	Gastrointestinal disorders	—	—
Mucositis oral	Gastrointestinal disorders	—	—
Fatigue	General disorders	—	—
Dysgeusia	Nervous system disorders	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
Palmar-plantar erythrodysesthesia syndrome	Skin and subcutaneous tissue disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—
Hypertension	Vascular disorders	—	—
Neutrophil count decreased	Investigations	—	—
Weight loss	Investigations	—	—
Hyperthyroidism	Endocrine disorders	—	—
Blurred vision	Eye disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Flatulence	Gastrointestinal disorders	—	—
Hypogeusia	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Flu like symptoms	General disorders	—	—
Pain	General disorders	—	—
Cellulitis, left knee	Infections and infestations	—	—
Lung infection	Infections and infestations	—	—
Upper respiratory infection	Infections and infestations	—	—
Gout, left knee	Musculoskeletal and connective tissue disorders	—	—
Headache	Nervous system disorders	—	—
Paresthesia	Nervous system disorders	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—
Hypotension	Vascular disorders	—	—

Most-reported serious reactions: Fatigue, Hypotension.

Data from ClinicalTrials.gov NCT03109015 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Drug-Induced Hypertension Caused by Multikinase Inhibitors (Sorafenib, Sunitinib, Lenvatinib and Axitinib) in Renal Cell Carcinoma Treatment.
   Bæk Møller N, Budolfsen C, Grimm D, Krüger M, et al · · 2019 · cited 43× · PMID 31547602 · DOI 10.3390/ijms20194712