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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether moderate exercise on the day of therapy can enhance the effectiveness of immunotherapy for skin cancers such as melanoma, squamous cell carcinoma, and Merkel cell carcinoma. Participants will either exercise for 30 minutes on a stationary bike before their treatment or receive standard care without exercise. The trial suits individuals scheduled for their first round of specific immunotherapy treatments who can already exercise for at least six minutes unaided. As an unphased trial, it provides a unique opportunity to contribute to innovative research that could improve cancer treatment outcomes.

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 prior data suggests that exercise is safe for patients with cutaneous cancers receiving immunotherapy?

Research has shown that exercise is generally safe and beneficial for cancer patients. Studies have found that physical activity can improve survival rates for those undergoing cancer immunotherapy and reduce the risk of serious immune-related side effects during treatment.

Exercise enhances both physical and mental health, lessening cancer symptoms and improving the body's response to treatment. Importantly, exercise does not cause major side effects, making it a well-tolerated option for many patients.

Overall, evidence for exercise in cancer care is promising, suggesting it is a safe addition to traditional treatment plans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about incorporating exercise into cancer immunotherapy because it offers a novel way to potentially boost treatment effectiveness. Unlike traditional cancer therapies that primarily rely on medication or radiation, this approach uses moderate exercise to enhance the body's natural immune response. The idea is that exercising before receiving checkpoint blockade immunotherapy might improve the therapy's ability to target and destroy cancer cells. This strategy is especially appealing because it's non-invasive and could be easily integrated into existing treatment regimens, offering a complementary method to enhance patient outcomes.

What evidence suggests that exercise might be an effective treatment for cutaneous cancers?

Research has shown that exercise can enhance the effectiveness of cancer treatments. In this trial, participants in the exercise arms will engage in moderate exercise before each administration of checkpoint blockade immunotherapy. One study found that 46.4% of people who exercised experienced full benefits from their treatment, compared to 30.8% who did not exercise. Other studies suggest that exercise can strengthen the immune system and make treatments like immunotherapy more effective. Evidence also indicates that regular exercise might reduce the risk of cancer recurrence. Overall, exercise plays an important role in improving cancer treatment and patient outcomes. ^{6 7 8 9 10}

Who Is on the Research Team?

Bret Goodpaster, PhD

Principal Investigator

Study Principal Investigator

Are You a Good Fit for This Trial?

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.

I have a severe heart condition that might make exercise unsafe without doctor's approval.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9397632/

Effects of Exercise on Cancer Treatment Efficacy Exploratory analyses found a numerically superior effect of exercise on the clinical complete response (46.4% exercise vs. 30.8% control; P = 0.24) in the 54 ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S209525462500047X

Exercise and cancer outcomes: What do we know and ... Consistent evidence exercise improves response to chemotherapy and immunotherapy in breast cancer. • Phase 1 data evaluating dose range and biological activity ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2646

Evaluating the role of exercise in modulating immunity and ... Conclusions: This review provides evidence that exercise may enhance immune responses and improve outcomes in cancer immunotherapy.

4. asco.org asco.org/about-asco/press-center/news-releases/movement-medicine-structured-exercise-program-challenge

Structured Exercise Program May Lower Risk of Cancer ... At five years, the disease-free survival rate was 80% in the structured exercise program and 74% in the health education materials group.

5. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1474770/full

Impact of exercise on cancer: mechanistic perspectives ... This review critically evaluates the substantial role of exercise in enhancing cancer prevention, treatment, and patient quality of life.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12579459/

A retrospective cohort study of physical activity and survival ... Pre-treatment physical activity is associated with increased survival among cancer patients treated with ICI. Observational studies ...

7. academic.oup.com academic.oup.com/jnci/article/116/4/573/7450125

Physical activity and checkpoint inhibition: association with ... Higher physical activity levels at the start of ICI treatment are associated with lower risk of severe irAEs and probably prolonged survival.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06152926

Physical Activity and Exercise in Cancer Immunotherapy ... It is well known that regular physical activity or planned exercise can help with these symptoms and significantly improve physical and mental health during ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8699800/

The Effects of Physical Activity on Cancer Patients ... All three murine studies indicated that physical activity slowed tumor growth, slowed immune cell proliferation, and improved immune sensitivity ...

10. jitc.bmj.com jitc.bmj.com/content/9/7/e001872

Exercise and the immune system: taking steps to improve ... There is substantial evidence that exercise and physical activity can reduce incidence and improve outcomes in cancer patients.