Ipilimumab and Nivolumab Combination Therapy With Supervised or Semi-supervised Exercise Intervention

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Collaborators:

Information provided by (Responsible Party):

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Tracking Information

First Submitted Date ^ICMJE

September 25, 2018

First Posted Date ^ICMJE

October 2, 2018

Last Update Posted Date

October 2, 2018

Actual Study Start Date ^ICMJE

November 1, 2018

Estimated Primary Completion Date

February 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Change in Cardiopulmonary function,[ Time Frame: Baseline, 13 weeks ]

Change in VO2 peak

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

Patient-reported fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale[ Time Frame: 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 activity as measured by the Godin Leisure Time Exercise Questionnaire[ Time Frame: 13 weeks ]
Patient-reported symptoms as measured by the Functional Assessment of Cancer Therapy-Kidney Symptom Index-19 (FKSI-19)[ Time Frame: 13 weeks ]
Patient health outcome as measured by the EQ-5D health questionnaire[ Time Frame: 13 weeks ]
Left ventricular ejection fraction (LVEF) at rest[ Time Frame: 13 weeks ]
Left ventricular ejection fraction (LVEF) during exercise[ Time Frame: 13 weeks ]
Cardiac function via 2D echocardiography[ Time Frame: 13 weeks ]
Cardiac function via 3D echocardiography[ Time Frame: 13 weeks ]
Upper extremity maximal muscular strength[ Time Frame: 13 weeks ]
Measured by a calculated one-repetition maximum (1-RM)
Lower extremity maximal muscular strength[ Time Frame: 13 weeks ]
Measured by a calculated one-repetition maximum (1-RM)
Cross-sectional area of the major muscles[ Time Frame: 13 weeks ]
Muscle endurance[ Time Frame: 13 weeks ]
Number of repetitions to fatigue at 70% of on-repetition maximum
Evaluate co-existent depression using the Hospital Anxiety and Depression (HADS) scale[ Time Frame: 13 weeks ]
The HADS scale consists of 14 statements that patients are asked to complete using statements that correlate to a score of 0 to 3, with high scores indicating higher levels of anxiety and/or depression
Eligibility rate[ Time Frame: 13 weeks ]
Eligibility rate is defined as the number of subjects eligible for the study divided by the number approached for the study (i.e., screen fail rate)
Attrition[ Time Frame: 13 weeks ]
The number of patients agreeing to participate divided by total number randomized
Compliance as measured by the number of ipilimumab doses taken[ Time Frame: 13 weeks ]
Compliance as measured by the number of nivolumab doses taken[ Time Frame: 13 weeks ]
Compliance as measured by the percent of ipilimumab doses taken[ Time Frame: 13 weeks ]
Compliance as measured by the percent of nivolumab doses taken[ Time Frame: 13 weeks ]
Exercise-related adverse event rate[ Time Frame: 13 weeks ]
Assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Dose intensity of nivolumab[ Time Frame: 13 weeks ]
Will be determined by evaluating treatment logs
Dose intensity of ipilimumab by evaluating treatment logs[ Time Frame: 13 weeks ]
Will be determined by evaluating treatment logs

Descriptive Information

Brief Title ^ICMJE

Ipilimumab and Nivolumab Combination Therapy With Supervised or Semi-supervised Exercise Intervention

Official Title ^ICMJE

INTENSE: 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

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 Type ^ICMJE

Interventional

Study Phase

N/A

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients will be assigned to one of three cohorts: Supervised exercise, semi-supervised exercise or usual care.
Masking: Interventional
Masking Description:
Primary Purpose: Supportive Care

Condition ^ICMJE

Intervention ^ICMJE

Behavioral: Exercise
Patients will be asked to complete 3 x 30 minute exercise sessions each week.

Study Arms

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.
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.
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.

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

February 1, 2021

Estimated Primary Completion Date

February 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria: - Age ≥18 years. - Histologically confirmed renal cell carcinoma (RCC). - Locally advanced, unresectable or metastatic disease, in the opinion of the investigator. - Scheduled to receive ipilimumab and nivolumab per standard of care. - No prior checkpoint inhibitor therapy for RCC. - Subjects with brain metastases are allowed if they are asymptomatic, without edema, and not on 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, in the opinion of the treating physician. - Must be able to complete an acceptable cardiopulmonary exercise test (CPET) at baseline (see Section 5.5) defined as at least one of the following: - Achieving a plateau in oxygen consumption concurrent with an increase in power output, or - A respiratory exchange ratio ≥ 1.1 (RER), or - Volitional exhaustion with a rating of perceived exertion ≥17 (RPE). - To participate in the optional fitness tracker cohort, the patient must either have a Bluetooth-enabled smart phone that is compatible with the wireless fitness tracker or be willing and able to upload data weekly via an internet-connected computer. - 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 study drug. - Palliative, focal radiation therapy less than 14 days prior to the first dose of study drug. - 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].

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

Plan to Share IPD:

Responsible Party

，

Study Sponsor ^ICMJE

Duke University

Collaborators ^ICMJE

Investigators ^ICMJE

Principal Investigator: Michael Harrison, MD Duke University

PRS Account

Verification Date

September 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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