Exercise + Immunotherapy for Cancer

Overseen By Stephanie Forgas

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must be taking: Checkpoint immunotherapy

Disqualifiers: Severe cardiovascular disease, major complications

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether 30 minutes of moderate exercise before each session of checkpoint blockade immunotherapy can enhance cancer treatment. Checkpoint blockade immunotherapy uses drugs to help the immune system fight cancer more effectively. The trial includes different groups: some will exercise before treatment, while others will not, to determine if exercise boosts the therapy's effects. Individuals with melanoma, cutaneous squamous cell carcinoma (cuSCC), or Merkel cell carcinoma who can perform moderate exercise and are starting immunotherapy for the first time might be suitable candidates. As an Early Phase 1 trial, this research focuses on understanding how exercise might enhance the effectiveness of immunotherapy in participants.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that participants should be scheduled for first-time checkpoint blockade immunotherapy without other therapies, which might imply some restrictions.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the immunotherapy used in this clinical trial is usually well-tolerated. Studies have found that about 20-25% of patients experience a strong and lasting positive response. Among the drugs used, nivolumab is known for its safety, particularly in treating lung cancer. However, like any treatment, side effects can occur, though serious ones are less common.

Exercise is often considered beneficial for cancer patients, as it can reduce treatment side effects and improve overall well-being. However, limited information exists about the risks of exercise for patients undergoing cancer treatment. Current evidence suggests that exercise is generally safe, but more research is needed to fully understand any potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining exercise with checkpoint blockade immunotherapy for cancer because it could enhance the body's immune response. While standard treatments like avelumab, nivolumab, or pembrolizumab target proteins that prevent the immune system from attacking cancer cells, adding moderate exercise might improve blood flow and immune cell activity, potentially boosting the effectiveness of these drugs. This approach not only utilizes the existing power of immunotherapy but also explores the potential synergistic effects of physical activity, offering a novel angle in cancer treatment strategies.

What evidence suggests that this trial's treatments could be effective for cancer?

This trial will compare the effects of combining exercise with checkpoint blockade immunotherapy to receiving the immunotherapy alone. Research has shown that combining exercise with checkpoint blockade immunotherapy could be promising. Studies have found that physical activity can slow tumor growth and enhance immune cell function. Additionally, starting treatment with higher activity levels is linked to fewer severe side effects and potentially longer survival. Exercise can help immune cells move toward tumors, increasing treatment effectiveness. Early findings suggest that exercise might boost the activity of key immune cells that fight cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Peter Kanetsky, PhD, MPH

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults who can read and speak English, give informed consent, and are able to do moderate exercise like walking unaided for at least six minutes. It's specifically for those with certain skin cancers or neuroendocrine carcinoma about to start checkpoint blockade immunotherapy. People with severe heart disease or major postoperative complications cannot join.

Inclusion Criteria

I am a patient with cutaneous squamous cell carcinoma.

I understand the study and can agree to participate.

I have Merkel cell carcinoma and am considering treatment before surgery.

Exclusion Criteria

I have a severe heart condition that may not allow for exercise.

I have major complications after surgery that may not allow me to exercise.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive up to 4 cycles of checkpoint blockade immunotherapy with or without exercise

Up to 4 months

Visits for each cycle, with blood samples collected at baseline, post-exercise, and post-infusion

Adjuvant Treatment

Participants receive 9-18 cycles of checkpoint blockade immunotherapy with or without exercise

Up to 12 months

Visits for each cycle, with blood samples collected at baseline, post-exercise, and post-infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Checkpoint Blockade Immunotherapy
• Exercise

Trial Overview The study tests if doing 30 minutes of moderate exercise before each dose of standard checkpoint blockade immunotherapy (drugs like avelumab, cemiplimab) improves treatment response in cancer patients.

How Is the Trial Designed?

Group I: Neoadjuvant Arm with Exercise Experimental Treatment 2 Interventions

Participants will complete 30 minutes of moderate exercise on an arm ergometer, a cycle ergometer, or a treadmill prior to each administration of standard of care checkpoint blockade immunotherapy across all cycles. Neoadjuvant participants will receive up to 4 cycles of therapy with avelumab, cemiplimab, ipilimumab, nivolumab, pembrolizumab, or relatlimab, or currently approved standard of care treatment, either alone or in combination. Blood samples will be collected at 1) baseline (upon arrival to clinic), 2) post-exercise, and 3) post-infusion. Blood samples will be obtained on the first and third infusion dates.

Group II: Adjuvant Arm with Exercise Experimental Treatment 2 Interventions

Participants will receive clinical care following Moffitt standards for the patient's disease type and therapeutic setting. Adjuvant participants will receive 1 year \[currently 9-18 cycles\] of therapy with avelumab, cemiplimab, ipilimumab, nivolumab, pembrolizumab or relatlimab, or currently approved standard of care treatment, either alone or in combination. Participants also will complete 30 minutes of moderate exercise on an arm ergometer, a cycle ergometer, or a treadmill prior to each administration of standard of care checkpoint blockade immunotherapy across all cycles. Blood samples will be collected at 1) baseline (upon arrival to clinic), 2) post-exercise, and 3) post-infusion. Blood samples will be obtained on the first, third, midpoint, and final infusion dates.

Group III: Neoadjuvant Arm without Exercise Active Control 1 Intervention

Participants will receive clinical care following Moffitt standards for the patient's disease type and therapeutic setting. Neoadjuvant participants will receive up to 4 cycles of therapy with avelumab, cemiplimab, ipilimumab, nivolumab, pembrolizumab, or relatlimab, or currently approved standard of care treatment, either alone or in combination. Participants also will complete 30 minutes of moderate exercise on an arm ergometer, a cycle ergometer, or a treadmill prior to each administration of standard of care checkpoint blockade immunotherapy across all cycles. Blood samples will be collected at 1) baseline (upon arrival to clinic), 2) post-exercise, and 3) post-infusion. Blood samples will be obtained on the first and third infusion dates.

Group IV: Adjuvant Arm without Exercise Active Control 1 Intervention

Participants will receive clinical care following Moffitt standards for the patients disease type and therapeutic setting. Adjuvant participants will receive one year \[currently 9-18 cycles\] of therapy with avelumab, cemiplimab, ipilimumab, nivolumab, pembrolizumab, relatlimab, or currently approved standard of care treatment, either alone or in combination. Blood samples will be collected at 1) baseline (upon arrival to clinic) and 2) post-infusion. Blood samples will be obtained on the first, third, midpoint, and final infusion dates.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Published Research Related to This Trial

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]

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]

Cancer immunotherapies, particularly anti-CTLA4 and anti-PD1/PD-L1, are becoming more common in treatment regimens, leading to increased exposure of patients to immune-related adverse events (irAEs).

These immunotherapies can activate the immune system to fight tumors effectively, but they also have a unique toxicity profile that can cause autoimmune reactions, necessitating changes in clinical management practices to address these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of adverse events associated with cancer immunotherapy]. Laparra, A., Champiat, S., Michot, JM., 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]

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 of 581 cancer patients treated with PD-1/PD-L1 inhibitors, 20% experienced endocrine adverse events (AEs), with pembrolizumab showing a significantly higher incidence of 38.5%.

Patients who developed endocrine AEs had better overall response rates (33.3% vs. 23.1%) and disease control rates (91.1% vs. 79.1%), suggesting that these AEs may be associated with a more favorable treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world retrospective study of incidence and associated factors of endocrine adverse events related to PD-1/PD-L1 inhibitors. Wang, Z., Hu, C., Zhang, A., 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]

Citations

1. 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 ...

2. 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.

3. link.springer.com link.springer.com/article/10.1007/s00520-025-09824-9

Objective measurement of physical activity levels and ... This study aimed to objectively assess physical activity levels in cancer patients treated with immune-checkpoint inhibitors (ICIs) and explore ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10526963/

Can Exercise Enhance the Efficacy of Checkpoint Inhibition by ... Results of recent studies indicate that physical activity can induce mobilization and redistribution of immune cells towards the tumor microenvironment (TME)

5. spj.science.org spj.science.org/doi/10.34133/research.0360

Crosstalk between Exercise and Immunotherapy Encouragingly, combining exercise with immune checkpoint blockade can reverse the TME and enhance effector CD8+ T cell infiltration and activity by increasing ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S205970292301311X

Comparison of clinical safety between standard versus ... Pharmacokinetic studies predicted similar safety between standard and extended immune checkpoint inhibitor dosing regimens.

7. nature.com nature.com/articles/s41591-024-03398-5

Prediction of checkpoint inhibitor immunotherapy efficacy ... In this study, we explored whether a machine learning system could predict ICI outcomes using routine blood tests and standard clinical variables.

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1200690

Safety, Activity, and Immune Correlates of Anti–PD-1 ... Our data show that approximately one in four to one in five patients treated with anti–PD-1 antibody had objective responses with durability; these occurred in ...

9. bmj.com bmj.com/content/363/bmj.k4226

Comparative safety of immune checkpoint inhibitors in cancer Compared with other ICI drugs used to treat cancer, atezolizumab had the best safety profile in general, and nivolumab had the best safety profile in lung ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5388381/

Safety and Tolerability of PD‐1/PD‐L1 Inhibitors Compared ... The development of immune checkpoint inhibitors represents a major breakthrough in cancer therapy. This systematic review and meta‐analysis of randomized ...