Exercise to Boost Response to Checkpoint Blockade Immunotherapy

Study Overview
=================
Brief Summary
-----------------
The purpose of this pilot study will be to provide i) information on feasibility implementing an exercise intervention trial among patients with cutaneous cancers, including melanoma, squamous cell carcinoma (cuSCC), and Merkel cell carcinoma, scheduled to receive checkpoint blockade immunotherapy, and ii) preliminary data on the impact of a day-of-therapy exercise intervention.

Official Title
-----------------
Exercise to Boost Response to Checkpoint Blockade Immunotherapy

Conditions
-----------------
Cutaneous Melanoma, Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma

Intervention / Treatment
-----------------
* Other: Exercise Test


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and females ≥18 years of age. Able to read and speak English fluently. Reported ability to complete 20-30 minutes moderate exercise per positive response to, Can you currently walk unaided for six minutes or more? Scheduled for first-time checkpoint blockade immunotherapy with avelumab, cemiplimab, ipilimumab, nivolumab, or pembrolizumab in the absence of other therapies (e.g. targeted therapy) with the following diagnosis: Adjuvant setting: cutaneous melanoma. Neoadjuvant setting: cutaneous melanoma, cuSCC, or Merkel cell carcinoma. States willingness to follow protocol as described, including the prescribed exercise level and completing any forms needed throughout the study. Voluntarily signed and dated an informed consent form, approved by an Institutional Review Board/Independent Ethics Committee, and provided Health Insurance Portability and Accountability Act authorization (HIPAA) or other privacy authorization prior to any participation in study. Exclusion Criteria: Presence of medical conditions, such as severe cardiovascular disease for which exercise may be contraindicated. Participants may be referred to their medical team to obtain a cardiology approval. Presence of major postoperative complications for which an exercise intervention may be contraindicated. Currently has a chronic, contagious, infectious disease, such as active tuberculosis, active Hepatitis B or C, HIV, or COVID-19, per self-report. Currently pregnant, lactating or planning to become pregnant (positive result on urine pregnancy testing). Presence of any condition that, in the opinion of the Investigator, compromises participant safety or data integrity or the participant's ability to complete the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: We will use stratified block randomization to assure non-biased assignment to the exercise intervention arm. Within each treatment setting, adjuvant and neoadjuvant, 10 patients will be randomized to the exercise intervention arm and 10 to the standard treatment arm. Within the neoadjuvant setting, randomization also will be blocked within disease type.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard Group- No Exercise (Adjuvant)<br>Patients randomized to the standard arm will receive clinical care following AH standards for the patient's disease type and therapeutic setting. This includes history and physical and laboratory studies to be conducted on each infusion day before clearing the patient for infusion. | |
| Active Comparator: Intervention Group- Moderate Exercise (adjuvant)<br>Patients randomized to the exercise arm will complete up to 30 minutes of same-day exercise prior to each administration of checkpoint blockade immunotherapy across all cycles. The preferred exercise is 30 minutes of moderate exertion on a cycle ergometer. | Other: Exercise Test<br>* Supervised pedaling on an ergometer (stationary bike) at a moderate pace for a goal of 30 minutes. The exercise test will be scheduled at infusion visits 1, 6, and 12 or 1 and 3 over the treatment cycle, depending on the group assignment.<br>|
| No Intervention: Standard Group- No Exercise (Neoadjuvant)<br>Patients randomized to the standard arm will receive clinical care following AH (AdventHealth) standards for the patient's disease type and therapeutic setting. This includes history and physical and laboratory studies to be conducted on each infusion day before clearing the patient for infusion. | |
| Active Comparator: Intervention Group- Moderate Exercise (Neoadjuvant)<br>Patients randomized to the exercise arm will complete up to 30 minutes of same-day exercise prior to each administration of checkpoint blockade immunotherapy across all cycles. The preferred exercise is 30 minutes of moderate exertion on a cycle ergometer. | Other: Exercise Test<br>* Supervised pedaling on an ergometer (stationary bike) at a moderate pace for a goal of 30 minutes. The exercise test will be scheduled at infusion visits 1, 6, and 12 or 1 and 3 over the treatment cycle, depending on the group assignment.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse-free survival | For patients treated in the adjuvant setting. Total study duration is dependent upon oncology therapy. Recurrence-free survival will be assessed. | Up to 12 months | 
| Pathological complete response (pCR) | For patients treated in the neoadjuvant setting. All neoadjuvant patients will have remaining tumor and, when appropriate, its associated nodal basin removed after completion of checkpoint blockade immunotherapy. Total study duration is dependent upon oncology therapy. This will be measured in excised tissues after standard-of-care surgery post completion of checkpoint blockade immunotherapy. | Up to 12 months |