INTERVAL: Ipilimumab and Nivolumab Combination Therapy: A Study of a Supervised or Semi-Supervised Exercise InteRVention or Usual Care With Functional Capacity and Quality of Life Evaluations in Subjects With Advanced or Metastatic RenAL Cell Carcinoma

Not Applicable

Terminated

• Conditions: Metastatic Renal Cell Carcinoma
• Interventions: Behavioral: Exercise

• Registration Number: NCT03692338
• Lead Sponsor: Duke University

Brief Summary

This study aims to report the effects of immediate or delayed exercise training on patients with advanced or metastatic renal cell carcinoma who are receiving nivolumab and ipilimumab.

Detailed Description

Exercise interventions also have been shown to improve both cancer- and treatment-related fatigue and quality of life across multiple tumor types. Thus, an exercise intervention could improve the tolerability of combination immunotherapy. Furthermore, functional capacity and/or amount of physical activity are associated with survival in several cancers. Finally, there is emerging evidence that exercise training may augment beneficial cancer-specific immune function. This study will examine parallel groups of supervised or semi-supervised exercise training or usual care in patients with mRCC treated with nivolumab and ipilimumab combination therapy. Fitness level will be evaluated by cardiopulmonary exercise testing (CPET), wearable exercise tracking devices and questionnaires after 12 weeks of semi-supervised, home-based exercise.

Study Timeline

• Study First Submitted: 2018-09-25
• Study First Submitted QC: 2018-09-28
• Study First Posted: 2018-10-02
• Study Start: 2018-11-19
• Status Verified: 2019-12
• Primary Completion: 2019-12-09
• Study Completion: 2019-12-09
• Last Update Submitted: 2019-12-16
• Last Update Posted: 2019-12-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

1. Age ≥18 years.

2. Scheduled to receive ipilumab and nivolumab as first line of immune checkpoint inhibitor therapy for Renal Cell Carcinoma (RCC).

   a. Patient may receive the first infusion of ipilimumab/nivolumab prior to eligibility determination

3. Subjects with brain metastases are allowed if they are asymptomatic, without edema, and not on greater than or equal to 10mg daily dose of systemic corticosteroids or receiving radiation therapy for at least 14 days prior to beginning protocol therapy.

4. Karnofsky Performance Status (KPS) of at least 70%

5. Able to walk on a treadmill per patient report.

6. Ability to understand English and the willingness to sign a written informed consent document.

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Exclusion Criteria

1. Major surgery (e.g. nephrectomy) less than 28 days prior to the first dose of ipilimumab/nivolumab.

2. History of cerebrovascular accident including transient ischemic attack (TIA) within the past 6 months.

3. Osseous metastatic disease with unacceptable risk of impending fracture due to study assessments, in the opinion of the investigator. Note: This criterion must be met prior to CPET.

4. Absolute contraindications to cardiopulmonary exercise testing and/or aerobic training, as determined by the attending oncologist:

   • Uncontrolled arrhythmia causing symptoms or hemodynamic compromise
   • Recurrent syncope
   • Active endocarditis
   • Acute myocarditis or pericarditis
   • Symptomatic severe aortic stenosis
   • Uncontrolled heart failure
   • Acute (within 3 months) pulmonary embolus or pulmonary infarction
   • Thrombosis of lower extremities
   • Suspected dissecting aneurysm
   • Uncontrolled asthma
   • Pulmonary edema
   • Room air desaturation at rest <85%
   • Respiratory failure
   • Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis)
   • Mental impairment leading to inability to cooperate.
   • Poorly controlled hypertension [defined as systolic blood pressure (SBP) of >150 mmHg or diastolic blood pressure (DBP) of >90 mmHg].

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
12 week semi-supervised exercise program	Exercise	This cohort will complete 12 weeks of a semi-supervised exercise program independently. Patients will be scheduled for an exercise session with a study exercise physiologist during clinical appointments to complete a sample intensity and time specific exercise session. The preferred mode will be walking, however cycling is also permitted. For each session the patient will wear a heart rate monitor. Following a 5 minute warm-up, patients will increase the intensity of exercise to reach a heart rate corresponding to approximately 60% VO2peak, and will continuously maintain this intensity for their individualized duration to elicit the desired energy expenditure. Each week, the exercise physiologist will call the patient and discuss how to approach the next set of exercise sessions. Additionally, patients will receive standard of care nivolumab (3 mg/kg i.v.) and ipilimumab (1 mg/kg i.v.) q3 weeks x 4 doses followed by nivolumab at 3 mg/kg q2 weeks.
12 week supervised exercise program	Exercise	Patients will be asked to complete 3 30-minute supervised exercise sessions/week under the guidance of the study exercise physiologist. The preferred mode will be treadmill walking, however, alternatives such as cycling or stair climbing machines will be used. For these sessions, patients will be asked to wear a heart rate monitor. Following a 5 minute warm-up, the exercise physiologist will increase speed to correspond with an intensity of approximately 80% VO2peak for 1-minute before returning to a lower speed for 1-minute (50% VO2peak). Patients will complete up to 20 of each 1-minute interval, then cool-down for 5 minutes. At the end of each higher intensity interval patients will be asked to rate their perceived exertion (RPE). Additionally, patients will receive standard of care nivolumab (3 mg/kg i.v.) and ipilimumab (1 mg/kg i.v.) q3 weeks x 4 doses followed by nivolumab at 3 mg/kg q2 weeks.

Primary Outcome Measures

Name	Time	Method
Change in Cardiopulmonary function	Baseline, 13 weeks	Change in VO2 peak

Secondary Outcome Measures

Name	Time	Method
Patient health outcome as measured by the EQ-5D health questionnaire	13 weeks	The EQ-5d is a patient-reported outcome tool to measure health
Patient-reported activity as measured by the Godin Leisure Time Exercise Questionnaire	13 weeks	The Godin Leisure is a patient-reported outcome tool to measure activity
Patient-reported activity as measured by the Stanford Brief Activity Survey	13 weeks	The Stanford Brief Activity Survey is a patient-reported outcome tool to measure activity
Patient-reported fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale	13 weeks	The FACIT-F measures severity and impact of fatigue on functioning and health-related quality of life experienced in past seven days using 40 statements that patients are asked to rate as 0-4 with 0 being "Not at all" and 4 being "Very much".
Patient-reported symptoms as measured by the Functional Assessment of Cancer Therapy-Kidney Symptom Index-19 (FKSI-19)	13 weeks	The FKSI-19 is a patient-reported outcome tool to measure symptoms of Cancer
Patient-reported activity as measured by the Incidental and Planned Activity Questionnaire	13 weeks	The Incidental and Planned Activity Questionnaire is a patient-reported outcome tool to measure activity

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States