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

NCT03109015 | Completed Phase 2 Results FDA Drug

• 1 other identifier: Pro00072588
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Carcinoma, Renal Cell

Keywords

metastatic renal cell carcinoma; sunitinib; Sutent; cardiopulmonary function

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, week 12

Secondary Outcomes (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

  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]

  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

  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

  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]

  Baseline, week 12

Study Arms (2)

Schedule 4/2

ACTIVE COMPARATOR

Drug: Sunitinib

Schedule 2/1

EXPERIMENTAL

Drug: Sunitinib

Interventions

Sunitinib DRUG

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.

Also known as: Sutent

Schedule 4/2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Histologically confirmed renal cell carcinoma (RCC)
• One of the two following populations:
• High risk for recurrence of RCC after nephrectomy, in the opinion of the investigator, OR
• Locally advanced, unresectable or metastatic disease, in the opinion of the investigator, and good or intermediate risk by IDMC Heng Criteria (see Appendix I).
• Karnofsky Performance Status (KPS) ≥ 80 (see Appendix A)
• Good or intermediate risk by IDMC Heng Criteria (see Appendix I).4
• Appropriate for treatment with sunitinib in the opinion of the treating physician.
• Able to swallow sunitinib and comply with study requirements.
• Able to walk and jog on a treadmill, in the opinion of the treating physician.
• Must be able to complete an acceptable cardiopulmonary exercise test (CPET) at baseline (see Section 8.2), defined as at least one of the following:
• Achieving a plateau in oxygen consumption concurrent with an increase in power output;
• Respiratory exchange ratio ≥ 1.1 (RER);
• Volitional exhaustion with a rating of perceived exertion ≥17 (RPE).
• Subjects must have normal organ and marrow function as defined below:

You may not qualify if:

• Any prior anti-VEGF therapies (i.e., sunitinib, sorafenib, pazopanib, axitinib, cabozantinib, bevacizumab, etc.), including in the adjuvant or neoadjuvant setting.
• Prior systemic therapy for advanced RCC; however, treatment with immunotherapy (i.e., high-dose bolus IL-2, ipilimumab + nivolumab, etc.) is allowed.
• Subjects who are receiving any other investigational agents.
• Subjects who are receiving strong CYP3A4 inhibitors or CYP3A4 inducers (see Section 5.3.2.2).
• Radiotherapy within 2 weeks prior to taking the first dose of study drug, or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
• Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic, and b) have no requirement for steroids or enzyme-inducing anticonvulsants in the prior 28 days.
• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
• Active peptic ulcer disease
• Known intraluminal metastatic lesion(s) with risk of bleeding
• Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions with increased risk of perforation
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment
• History of any one or more of the following cardiovascular conditions within the past 6 months:
• Cardiac angioplasty or stenting
• Myocardial infarction
• Unstable angina

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke Cancer Institute

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Sunitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Michael Harrison, MD
• Organization: Duke University

michael.harrison@duke.edu

919-668-8108

Study Officials

• Michael Harrison, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2017
• First Posted: April 11, 2017
• Study Start: September 27, 2017
• Primary Completion: October 8, 2019
• Study Completion: October 8, 2019
• Last Updated: October 8, 2024
• Results First Posted: December 17, 2020

Record last verified: 2024-09

Locations

US (1)