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 (INTERVAL)

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Renal Cell Carcinoma
• Intervention / Treatment: Behavioral: Exercise

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 Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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].

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 12 week supervised exercise program; 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.	Behavioral: Exercise; Patients will be asked to complete 3 x 30 minute exercise sessions each week.
EXPERIMENTAL: 12 week semi-supervised exercise program; 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.	Behavioral: Exercise; Patients will be asked to complete 3 x 30 minute exercise sessions each week.
NO_INTERVENTION: Control cohort; Participants will have routine care for 12 weeks. This will consist of 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cardiopulmonary function	Change in VO2 peak	Baseline, 13 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale	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".	13 weeks
Patient-reported activity as measured by the Godin Leisure Time Exercise Questionnaire	The Godin Leisure is a patient-reported outcome tool to measure activity	13 weeks
Patient-reported symptoms as measured by the Functional Assessment of Cancer Therapy-Kidney Symptom Index-19 (FKSI-19)	The FKSI-19 is a patient-reported outcome tool to measure symptoms of Cancer	13 weeks
Patient health outcome as measured by the EQ-5D health questionnaire	The EQ-5d is a patient-reported outcome tool to measure health	13 weeks
Patient-reported activity as measured by the Stanford Brief Activity Survey	The Stanford Brief Activity Survey is a patient-reported outcome tool to measure activity	13 weeks
Patient-reported activity as measured by the Incidental and Planned Activity Questionnaire	The Incidental and Planned Activity Questionnaire is a patient-reported outcome tool to measure activity	13 weeks

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 19, 2018
• Primary Completion (ACTUAL): December 9, 2019
• Study Completion (ACTUAL): December 9, 2019

Study Registration Dates

• First Submitted: September 25, 2018
• First Submitted That Met QC Criteria: September 28, 2018
• First Posted (ACTUAL): October 2, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 18, 2019
• Last Update Submitted That Met QC Criteria: December 16, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: exercise; nivolumab; ipilimumab; metastatic renal cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma
• Other Study ID Numbers: Pro00082941

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No