Metastatic Melanoma
Conditions
Keywords
exercise, Immunotherapy, Melanoma, Nivolumab, Ipilimumab
Brief summary
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.
Interventions
BEHAVIORAL30 Minutes Cycle Ergometer
Moderate physical activity for 30 minutes on a cycle ergometer
Sponsors
Universitätsklinikum Hamburg-Eppendorf
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed metastatic malignant melanoma with an indication for immunotherapy (Nivolumab and Ipilimumab). * The participant provides written informed consent for the study. * The participant is at least 18 years of age on the day the informed consent is signed. * No prior systemic anticancer therapy for metastatic disease (e.g., cytotoxic or targeted agents). * ECOG (Eastern Cooperative Oncology Group) performance status score of ≤ 2. * No physical impairment that would preclude participation in physical exercise.
Exclusion criteria
* Major surgery within 2 weeks prior to the start of the study intervention, or participants who have not fully recovered from the effects of a previous surgery. * Participants with a diagnosed immunodeficiency, or those receiving chronic systemic corticosteroid therapy (at a dose greater than 10 mg prednisone equivalent per day), or any other form of immunosuppressive therapy within 7 days prior to the first dose of the study medication. * Participants with an active infection requiring systemic therapy. * Participants with a known history of infection with human immunodeficiency virus (HIV) or hepatitis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility rate | 9 weeks | Rate of \>70% |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS | Time from randomization to progression or death from any cause, up to 30 months. | Median time is reported |
| 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 | Difference calculated between blood draw directly before and directly after sport intervention. | — |
| OS | Time from randomization to progression or death from any cause, up to 30 months. | Median OS is reported. |
| Increase of cytokines and chemokines, i.e. IL-15 after cycling | Difference measured from the blood draw directly before and the blood draw directly after the sport intervention. | Absolute concentrations |
| Side effects | 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. | Amount of patients and fraction experiencing AE and grade according to CTCAE v4.0 is reported. |
Countries
Germany
Contacts
CONTACTJoseph Tintelnot, MD
CONTACTJulian Kött, MD
Outcome results
None listed