Exercise for Cancer Immunotherapy Response

(EX-BOOST Trial)

Overseen By Recruitment Department

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: AdventHealth Translational Research Institute

Must be taking: Checkpoint immunotherapy

Disqualifiers: Severe cardiovascular disease, Infectious disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 12 months

20 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It might be best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Exercise, Physical Activity, Workout, Fitness Training for improving cancer immunotherapy response?

Research shows that exercise can enhance the immune system's response to cancer treatments by improving blood flow to tumors and increasing the activity of immune cells. This suggests that exercise may help make cancer immunotherapy more effective. ^{1 2 3 4 5}

Is exercise safe for humans in the context of cancer immunotherapy?

Exercise is generally considered safe for humans and has been shown to improve outcomes in cancer patients by enhancing the immune system. While specific safety data for exercise combined with cancer immunotherapy is limited, exercise is widely recognized for its health benefits and is associated with reduced cancer recurrence and mortality. ^{1 2 3 6 7}

How does exercise as a treatment differ from other cancer treatments?

Exercise is unique as a cancer treatment because it enhances the body's immune response and improves blood flow to tumors, potentially boosting the effectiveness of immunotherapy. Unlike traditional treatments like chemotherapy or radiation, exercise is a non-invasive approach that can be used alongside other therapies to improve outcomes. ^{1 2 3 8 9}

Research Team

Bret Goodpaster, PhD

Principal Investigator

Study Principal Investigator

Eligibility Criteria

This trial is for adults over 18 who speak English and are about to start checkpoint blockade immunotherapy for the first time, targeting skin cancers like melanoma. They must be able to do moderate exercise, follow the study protocol, and not have severe health issues that make exercise unsafe.

Inclusion Criteria

I have signed the consent form and agreed to share my health information for this study.

States willingness to follow protocol as described, including the prescribed exercise level and completing any forms needed throughout the study

I can walk unaided for six minutes or more.

Exclusion Criteria

I have major complications after surgery that may prevent me from exercising.

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

Currently pregnant, lactating or planning to become pregnant (positive result on urine pregnancy testing)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive checkpoint blockade immunotherapy with or without a same-day exercise intervention

Up to 12 months

Visits coincide with each immunotherapy cycle

Follow-up

Participants are monitored for relapse-free and recurrence-free survival

Up to 12 months

Treatment Details

Interventions

• Exercise

Trial Overview The study tests if exercising on the day you get immunotherapy (with drugs like avelumab or pembrolizumab) is feasible and affects treatment outcomes in patients with certain skin cancers.

Participant Groups

Group I: Intervention Group- Moderate Exercise (adjuvant) Active Control 1 Intervention

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.

Group II: Intervention Group- Moderate Exercise (Neoadjuvant) Active Control 1 Intervention

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.

Group III: Standard Group- No Exercise (Neoadjuvant) Active Control 1 Intervention

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.

Group IV: Standard Group- No Exercise (Adjuvant) Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

AdventHealth Translational Research Institute

Lead Sponsor

Trials

51

Recruited

5,900+

Findings from Research

Observational studies suggest that both physical activity and structured exercise can significantly reduce the risk of cancer recurrence and mortality, highlighting their potential role in cancer recovery.

Emerging preclinical evidence indicates that exercise may enhance the effectiveness of standard cancer treatments like chemotherapy and radiotherapy by improving tumor blood flow, oxygen levels, and immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise as Adjunct Therapy in Cancer. Ashcraft, KA., Warner, AB., Jones, LW., et al.[2020]

Exercise and physical activity can enhance immune function in cancer patients, potentially improving their responses to immunotherapies like immune checkpoint inhibitors and CAR T cell therapies.

Chronic exercise is linked to better physical fitness and a healthier immune profile, including reduced dysfunctional T cells, suggesting that incorporating exercise into cancer treatment plans could lead to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise and the immune system: taking steps to improve responses to cancer immunotherapy. Gustafson, MP., Wheatley-Guy, CM., Rosenthal, AC., et al.[2023]

In a study involving mice with breast and melanoma tumors, exercise combined with anti-PD-1 immunotherapy increased the percentage of CD8+ T cells in breast tumors, suggesting a potential enhancement of anti-tumor immune responses.

The effects of exercise on the immune environment varied by tumor type, indicating that while exercise may improve the efficacy of immunotherapy in some cancers, its impact is not uniform across different tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exercise and anti-PD-1 on the tumour microenvironment. Buss, LA., Williams, T., Hock, B., et al.[2022]

Exercise may enhance the effectiveness of immune checkpoint inhibition (ICI) in cancer therapy by promoting the movement and distribution of immune cells to the tumor microenvironment, potentially improving anti-tumor immunity.

The review highlights the importance of various factors such as cancer type, exercise frequency, intensity, time, and type (FITT) in determining how exercise influences cancer immunosurveillance and the response to ICI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can Exercise Enhance the Efficacy of Checkpoint Inhibition by Modulating Anti-Tumor Immunity? Brummer, C., Pukrop, T., Wiskemann, J., et al.[2023]

In a study using a mouse model of triple negative breast cancer, exercise was found to slow tumor progression and reduce the accumulation of myeloid-derived suppressor cells (MDSCs), which are known to suppress immune responses.

Exercise also enhanced the activation of natural killer and CD8 T cells, suggesting it helps create a more favorable immune environment, and improved responses to treatments like PD-1 blockade and radiotherapy, indicating potential benefits for breast cancer patients undergoing similar therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise reduces immune suppression and breast cancer progression in a preclinical model. Wennerberg, E., Lhuillier, C., Rybstein, MD., et al.[2020]

In a study of 251 patients undergoing immune checkpoint inhibitor (ICI) treatment, higher levels of physical activity were linked to a significantly lower risk of severe immune-related adverse events (irAEs), with moderate and high activity reducing the odds by up to 81%.

Patients with higher physical activity levels also experienced prolonged overall survival, suggesting that engaging in more physical activity at the start of ICI treatment may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical activity and checkpoint inhibition: association with toxicity and survival. Verheijden, RJ., Cabané Ballester, A., Smit, KC., et al.[2023]

A review of six studies on cancer survivors indicated that physical exercise may lead to significant improvements in various immune system components, which could enhance the body's anticancer response.

Despite some positive findings, the studies had limitations in their design and assessments, highlighting the need for further research to confirm whether exercise can effectively reduce cancer recurrence and improve survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical exercise and immune system function in cancer survivors: a comprehensive review and future directions. Fairey, AS., Courneya, KS., Field, CJ., et al.[2022]

Regular exercise has been shown to lower the risk of cancer, potentially by enhancing the body's immune response against tumors.

Recent studies indicate that exercise may improve the function of immune cells that target cancer, which is crucial as immunotherapy becomes a key part of cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise Benefits Meet Cancer Immunosurveillance: Implications for Immunotherapy. Fiuza-Luces, C., Valenzuela, PL., Castillo-García, A., et al.[2021]

Physical exercise can positively influence the immune system within tumors, leading to tumor suppression by enhancing the functions of immune cells like macrophages and natural killer cells.

There is potential for combining exercise with cancer immunotherapies, but further research is needed to determine the optimal exercise parameters and to explore its effects on various immune cell types in human tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise-Induced Changes in Tumor Growth via Tumor Immunity. Spiliopoulou, P., Gavriatopoulou, M., Kastritis, E., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Exercise as Adjunct Therapy in Cancer. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Exercise and the immune system: taking steps to improve responses to cancer immunotherapy. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of exercise and anti-PD-1 on the tumour microenvironment. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Can Exercise Enhance the Efficacy of Checkpoint Inhibition by Modulating Anti-Tumor Immunity? [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Exercise reduces immune suppression and breast cancer progression in a preclinical model. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Physical activity and checkpoint inhibition: association with toxicity and survival. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Physical exercise and immune system function in cancer survivors: a comprehensive review and future directions. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Exercise Benefits Meet Cancer Immunosurveillance: Implications for Immunotherapy. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Exercise-Induced Changes in Tumor Growth via Tumor Immunity. [2021]