Clinical trial NCT03692338: 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
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
Overall status: TERMINATED
Phase: NA
Conditions: Metastatic Renal Cell Carcinoma
Keywords: metastatic renal cell carcinoma
ipilimumab
nivolumab
exercise
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2018-10-02
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be assigned to one of three cohorts: Supervised exercise, semi-supervised exercise or usual care.
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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 \[defined as systolic blood pressure (SBP) of \>150 mmHg or diastolic blood pressure (DBP) of \>90 mmHg\].

Primary outcomes:
measure: Change in Cardiopulmonary function
timeFrame: Baseline, 13 weeks
Secondary outcomes:
measure: Patient-reported fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale
timeFrame: 13 weeks
measure: Patient-reported activity as measured by the Godin Leisure Time Exercise Questionnaire
timeFrame: 13 weeks
measure: Patient-reported symptoms as measured by the Functional Assessment of Cancer Therapy-Kidney Symptom Index-19 (FKSI-19)
timeFrame: 13 weeks
measure: Patient health outcome as measured by the EQ-5D health questionnaire
timeFrame: 13 weeks
measure: Patient-reported activity as measured by the Stanford Brief Activity Survey
timeFrame: 13 weeks
measure: Patient-reported activity as measured by the Incidental and Planned Activity Questionnaire
timeFrame: 13 weeks
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Michael Harrison, MD
role: PRINCIPAL_INVESTIGATOR
References: