search
Back to results

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)

Primary Purpose

Metastatic Renal Cell Carcinoma

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Exercise
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Metastatic Renal Cell Carcinoma focused on measuring metastatic renal cell carcinoma, ipilimumab, nivolumab, exercise

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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].

Sites / Locations

  • Duke University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

No Intervention

Arm Label

12 week supervised exercise program

12 week semi-supervised exercise program

Control cohort

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Change in Cardiopulmonary function
Change in VO2 peak

Secondary Outcome Measures

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".
Patient-reported activity as measured by the Godin Leisure Time Exercise Questionnaire
The Godin Leisure is a patient-reported outcome tool to measure activity
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
Patient health outcome as measured by the EQ-5D health questionnaire
The EQ-5d is a patient-reported outcome tool to measure health
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
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

Full Information

First Posted
September 25, 2018
Last Updated
December 16, 2019
Sponsor
Duke University
Collaborators
Bristol-Myers Squibb
search

1. Study Identification

Unique Protocol Identification Number
NCT03692338
Brief Title
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
Acronym
INTERVAL
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Terminated
Why Stopped
Poor accrual
Study Start Date
November 19, 2018 (Actual)
Primary Completion Date
December 9, 2019 (Actual)
Study Completion Date
December 9, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
Bristol-Myers Squibb

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Renal Cell Carcinoma
Keywords
metastatic renal cell carcinoma, ipilimumab, nivolumab, exercise

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Patients will be assigned to one of three cohorts: Supervised exercise, semi-supervised exercise or usual care.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
12 week supervised exercise program
Arm Type
Experimental
Arm Description
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.
Arm Title
12 week semi-supervised exercise program
Arm Type
Experimental
Arm Description
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.
Arm Title
Control cohort
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Exercise
Intervention Description
Patients will be asked to complete 3 x 30 minute exercise sessions each week.
Primary Outcome Measure Information:
Title
Change in Cardiopulmonary function
Description
Change in VO2 peak
Time Frame
Baseline, 13 weeks
Secondary Outcome Measure Information:
Title
Patient-reported fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale
Description
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".
Time Frame
13 weeks
Title
Patient-reported activity as measured by the Godin Leisure Time Exercise Questionnaire
Description
The Godin Leisure is a patient-reported outcome tool to measure activity
Time Frame
13 weeks
Title
Patient-reported symptoms as measured by the Functional Assessment of Cancer Therapy-Kidney Symptom Index-19 (FKSI-19)
Description
The FKSI-19 is a patient-reported outcome tool to measure symptoms of Cancer
Time Frame
13 weeks
Title
Patient health outcome as measured by the EQ-5D health questionnaire
Description
The EQ-5d is a patient-reported outcome tool to measure health
Time Frame
13 weeks
Title
Patient-reported activity as measured by the Stanford Brief Activity Survey
Description
The Stanford Brief Activity Survey is a patient-reported outcome tool to measure activity
Time Frame
13 weeks
Title
Patient-reported activity as measured by the Incidental and Planned Activity Questionnaire
Description
The Incidental and Planned Activity Questionnaire is a patient-reported outcome tool to measure activity
Time Frame
13 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥18 years. 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 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. Karnofsky Performance Status (KPS) of at least 70% Able to walk on a treadmill per patient report. Ability to understand English and the willingness to sign a written informed consent document. Exclusion Criteria: Major surgery (e.g. nephrectomy) less than 28 days prior to the first dose of ipilimumab/nivolumab. History of cerebrovascular accident including transient ischemic attack (TIA) within the past 6 months. 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. 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].
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Harrison, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs