The aim of this research project is to determine whether a short bout of physical exercise immediately before the start of immunotherapy (Nivolumab and Ipilimumab) is feasible and has a positive effect on the effectiveness of immunotherapy. It is known that short-term physical exercise leads to marked changes in the innate and adaptive immune system. These changes-specifically an increase in natural killer (NK) cells and cytotoxic T cells-are associated with a better response to immunotherapy. The patient population selected for this study consists of patients with advanced-stage melanoma who are receiving Nivolumab and Ipilimumab. First, we aim to assess whether such an intervention is feasible in a large proportion of patients, as many patients experience disease-related and treatment-related side effects. Secondary objectives are to demonstrate that the exercise intervention positively influences the immune system and that this, in turn, leads to an improved response to therapy, thereby positively affecting patient survival, improving quality of life, and reducing treatment-related side effects.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
40
Moderate physical activity for 30 minutes on a cycle ergometer
University Medical Center Hamburg-Eppendorf
Hamburg, Free and Hanseatic City of Hamburg, Germany
RECRUITINGFeasibility rate
Rate of \>70%
Time frame: 9 weeks
PFS
Median time is reported
Time frame: Time from randomization to progression or death from any cause, up to 30 months.
Increase of NK cells and T cells or T cell subsets auch as CD103/CD39-positive CD8 T cells in the peripheral blood after cycling
Time frame: Difference calculated between blood draw directly before and directly after sport intervention.
OS
Median OS is reported.
Time frame: Time from randomization to progression or death from any cause, up to 30 months.
Increase of cytokines and chemokines, i.e. IL-15 after cycling
Absolute concentrations
Time frame: Difference measured from the blood draw directly before and the blood draw directly after the sport intervention.
Side effects
Amount of patients and fraction experiencing AE and grade according to CTCAE v4.0 is reported.
Time frame: Occurrence of side effects during active therapy with nivolumab and ipilimumab; the rate per patient is calculated from randomization to the end of the trial. Up to 30 months.
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