Phase 2 Completed N=7 Randomized Treatment

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

Carcinoma, Renal Cell

Source: ClinicalTrials.gov NCT03109015 ↗

Enrolled (actual)

Serious AEs

28.6%

Results posted

Dec 2020

Primary outcomePrimary: Change in Relative VO2 Peak From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules — -1.13; 1.27 mL/kg/min

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.

Outcome Measures

Outcome	Result	p-value
PRIMARY Change in Relative VO2 Peak From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules	-1.13; 1.27	—
SECONDARY 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	1.5; -9.0	—
SECONDARY 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]	—	—
SECONDARY 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	7; 6.67; -6.5; -6.0; 52.25; 15	—
SECONDARY 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	1.25; 4.33; -4.5; -4.0; 36.5; 10.33	—
SECONDARY 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]	—	—
SECONDARY 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	-0.43; -2.05	—
SECONDARY 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	-0.5; 0	—
SECONDARY 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	1.43; -69.2	—
SECONDARY 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	-2.89; -2.87	—
SECONDARY 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	2.75; -1.0	—
SECONDARY Change in Hospital Anxiety and Depression Survey (HADS) Score From Baseline to Week 12 in the 4/2 and 2/1 Sunitinib Administration Schedules	0.75; 0.3; 0.0; 1.3	—
SECONDARY 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	1.67; 0.5	—

Eligibility Criteria

Inclusion Criteria

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:
Absolute neutrophil count ≥1,200/µL
Hemoglobin ≥9 g/dL
Platelets ≥75,000/µL
Total bilirubin ≤1.5 x institutional upper limit of normal
AST(SGOT)/ALT(SGPT) 30 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal (see Appendix H).
Left ventricular ejection fraction (LVEF) ≥lower limit of institutional normal as assessed by echocardiography.
For the sixteen patients who elect to participate in the optional technology portion involving electronic step counts and blood pressure monitoring, the patient must have a Bluetooth-enabled smart phone, which is compatible with the wireless health monitors.
For women of childbearing potential (WOCBP) must have a negative serum pregnancy test prior to the start of the study. Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of the study. Medically acceptable contraceptives include: (1) surgical sterilization (such as a tubal ligation or hysterectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD). Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are not acceptable methods for routine use. If you do become pregnant during this study or if you have unprotected sex, you must inform your study physician immediately.
For men who are sexually active, must agree to use a two medically acceptable forms of birth control (one of which must include a condom as a barrier method of contraception) in order to be in this study. Medically acceptable contraceptives include: (1) surgical sterilization (such as a vasectomy), or (2) a condom used with a spermicide. Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are not acceptable methods for routine use. Men must also agree to inform their partner of the potential for harm to an unborn child. She should know that if pregnancy occurs, the subject will need to report it to the study doctor, and she should promptly notify her doctor. The study doctor will ask if the subject's partner is willing to provide updates on the progress of the pregnancy and its outcome. If the subject's partner agrees, this information will be provided to Pfizer, Inc. for safety monitoring follow-up.

Exclusion Criteria

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 receiv

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Data sourced from ClinicalTrials.gov (NCT03109015). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.