Exercise for Cancer Immunotherapy Response
(EX-BOOST Trial)
Recruiting in Palo Alto (17 mi)
Overseen byBret Goodpaster, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: AdventHealth Translational Research Institute
Must be taking: Checkpoint immunotherapy
Disqualifiers: Severe cardiovascular disease, Infectious disease, Pregnancy, others
No Placebo Group
Approved in 1 Jurisdiction
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.
12345Is 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.
12367How 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.
12389Eligibility 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
Able to read and speak English fluently
+3 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)
+2 more
Trial 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
Participant Groups
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.
4Treatment groups
Active Control
Group I: Intervention Group- Moderate Exercise (adjuvant)Active Control1 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 Control1 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 Control1 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 Control1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
AdventHealth Translational Research InstituteOrlando, FL
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Who Is Running the Clinical Trial?
AdventHealth Translational Research InstituteLead Sponsor
References
Exercise as Adjunct Therapy in Cancer. [2020]Data from observational studies indicate that both physical activity as well as exercise (ie, structured physical activity) is associated with reductions in the risk of recurrence and cancer mortality after a diagnosis of certain forms of cancer. Emerging evidence from preclinical studies indicates that physical activity/exercise paradigms regulate intratumoral vascular maturity and perfusion, hypoxia, and metabolism and augments the antitumor immune response. Such responses may, in turn, enhance response to standard anticancer treatments. For instance, exercise improves efficacy of chemotherapeutic agents, and there is rationale to believe that it will also improve radiotherapy response. This review overviews the current preclinical as well as clinical evidence supporting exercise modulation of therapeutic response and postulated biological mechanisms underpinning such effects. We also examine the implications for tumor response to radiation, chemotherapy, and immunotherapy.
Exercise and the immune system: taking steps to improve responses to cancer immunotherapy. [2023]The remarkable success of cancer immunotherapies has provided new hope to cancer patients. Unfortunately, a significant proportion of patients remain unable to respond to immunotherapy or maintain durable clinical responses. The lack of objective responses likely results from profound immune dysfunction often observed in patients with cancer. There is substantial evidence that exercise and physical activity can reduce incidence and improve outcomes in cancer patients. As the immune system is highly responsive to exercise, one potential avenue to improve immune function is through exercise and physical activity. A single event of dynamic exercise results in the substantial mobilization of leukocytes with increased functional capacities into the circulation. Chronic, or long-term, exercise leads to higher physical fitness in terms of greater cardiorespiratory function and/or muscle strength and endurance. High aerobic capacity, as measured by maximal oxygen uptake, has been associated with the reduction of dysfunctional T cells and improvements in the abundance of some T cell populations. To be sure, however, the mechanisms of exercise-mediated immune changes are both extensive and diverse. Here, we examine the evidence and theorize how acute and chronic exercise could be used to improve responses to cancer immunotherapies including immune checkpoint inhibitors, dendritic cell vaccines, natural killer cell therapies, and adoptive T cell therapies such as chimeric antigen receptor (CAR) T cells. Although the parameters of optimal exercise to yield defined outcomes remain to be determined, the available current data provide a compelling justification for additional human studies and clinical trials investigating the adjuvant use of exercise in immuno-oncology.
Effects of exercise and anti-PD-1 on the tumour microenvironment. [2022]Immune checkpoint inhibition is highly effective in treating a subset of patients with certain cancers, such as malignant melanoma. However, a large proportion of patients will experience treatment resistance, and other tumour types, such as breast cancer, have thus far proven largely refractory to immune checkpoint inhibitors as single agents. Exercise has been associated with improved cancer patient survival, has known immune-modulatory effects, may improve anti-tumour immunity and may normalise tumour blood vessels. Therefore, we hypothesised that post-implant exercise would boost the effect of concurrent immunotherapy by enhancing anti-tumour immune responses and improving tumour blood flow. To investigate this, mice with EO771 breast tumours or B16-F10 melanomas received anti-PD-1, an isotype control antibody or no treatment. Mice were randomised to exercise (voluntary wheel running) or no exercise at tumour implant. Exercise reduced the number of CD8+T cells in EO771 (p = 0.0011) but not B16-F10 tumours (p = 0.312), and reduced the percentage of CD8+T cells within the total T cell population in both tumour types (B16-F10: p = 0.0389; EO771: p = 0.0015). In contrast, the combination of exercise and anti-PD-1 increased the percentage of CD8+T cells in EO771 (p = 0.0339) but not B16-F10 tumours. Taken together, our results show that exercise and anti-PD-1 induce changes in the tumour immune microenvironment which are dependant on tumour type.
Can Exercise Enhance the Efficacy of Checkpoint Inhibition by Modulating Anti-Tumor Immunity? [2023]Immune checkpoint inhibition (ICI) has revolutionized cancer therapy. However, response to ICI is often limited to selected subsets of patients or not durable. Tumors that are non-responsive to checkpoint inhibition are characterized by low anti-tumoral immune cell infiltration and a highly immunosuppressive tumor microenvironment. Exercise is known to promote immune cell circulation and improve immunosurveillance. Results of recent studies indicate that physical activity can induce mobilization and redistribution of immune cells towards the tumor microenvironment (TME) and therefore enhance anti-tumor immunity. This suggests a favorable impact of exercise on the efficacy of ICI. Our review delivers insight into possible molecular mechanisms of the crosstalk between muscle, tumor, and immune cells. It summarizes current data on exercise-induced effects on anti-tumor immunity and ICI in mice and men. We consider preclinical and clinical study design challenges and discuss the role of cancer type, exercise frequency, intensity, time, and type (FITT) and immune sensitivity as critical factors for exercise-induced impact on cancer immunosurveillance.
Exercise reduces immune suppression and breast cancer progression in a preclinical model. [2020]Exercise is associated with favorable changes in circulating immune cells and improved survival in early-stage breast cancer patients, but the mechansims remain to be fully elucidated. Preclinical studies indicate that physical activity started before tumor injection reduces tumor incidence and progression. Here we tested whether exercise has anti-tumor effects in mice with established 4T1 mammary carcinoma, a mouse model of triple negative breast cancer. Exercise slowed tumor progression and reduced the tumor-induced accumulation of myeloid-derived suppressor cells (MDSCs). The reduction in MDSCs was accompanied by a relative increase in natural killer and CD8 T cell activation, suggesting that exercise restores a favorable immune environment. Consistently, exercise improved responses to a combination of programmed cell death protein 1 (PD-1) blockade and focal radiotherapy. These data support further investigations of exercise in breast cancer patients treated with combinations of immunotherapy and cytotoxic agents to improve cancer outcomes.
Physical activity and checkpoint inhibition: association with toxicity and survival. [2023]While animal experiments suggest beneficial effects of physical activity (PA) on anti-tumor immunity, little is known about the effects of PA on immune checkpoint inhibitor (ICI) toxicity and effectiveness in humans. We assessed the association of PA with immune-related adverse events (irAE) and survival in patients undergoing ICI.
Physical exercise and immune system function in cancer survivors: a comprehensive review and future directions. [2022]There are a limited number of interventions for cancer survivors following completion of primary therapy that might reduce the risk of cancer recurrence and/or secondary malignancies and increase survival times. It has been proposed that physical exercise may be beneficial by enhancing the anticancer immune system response. The purpose of the current article is to: 1) briefly describe the immune system response to tumors, 2) discuss the impact of anticancer therapy on immune system function in cancer survivors, 3) provide a systematic and comprehensive review of the extant literature examining physical exercise and immune system function in cancer survivors, and 4) offer a critical analysis of this literature and outline directions for future research.
Exercise Benefits Meet Cancer Immunosurveillance: Implications for Immunotherapy. [2021]Regular exercise reduces the risk of cancer. One potential mechanism for this efficacy is improved antitumor immunity. This is an important issue because evading immune destruction is a hallmark of cancer and immunotherapy is reshaping cancer treatment. Here we review recent developments reported by Wennerberg et al., Garritson et al., Martín-Ruiz et al., and Rundqvist et al. on the effects of exercise on anticancer immune cell effectors.
Exercise-Induced Changes in Tumor Growth via Tumor Immunity. [2021]Immunity in the tumor microenvironment plays a central role in tumor development. Cytotoxic immune cells act against tumors, while tumors manage to trigger immunosuppressive mechanisms for defense. One bout of physical exercise acutely regulates the immune system inducing short-term redistribution of immune cells among body organs. Repeated acute immune cell mobilization with continuing exercise training results in long-term adaptations. These long-term exercise-induced changes in the immune system arise both in healthy and in diseased populations, including cancer patients. Recent preclinical studies indicate that physical exercise may have a positive impact on intra-tumoral immune cell processes, resulting in tumor suppression. This short narrative review describes the effect of physical exercise on tumor growth as detected via changes in tumor immunity. Research evidence shows that exercise may improve tumor-suppressive functions and may reduce tumor-progressive responses and mechanisms of immune cells, controlling tumor development. Specifically, it seems that exercise in rodents triggers shifts in tumor infiltration of macrophages, neutrophils, natural killer cells, cytotoxic and regulatory T lymphocytes, resulting in tumor suppression. These recent promising data suggest that physical exercise could be combined with anticancer immunotherapies, although exercise parameters like intensity, duration, and frequency need to be evaluated in more detail. More research is needed to investigate the effect of exercise in other immune cell subtypes and their possible connection with tumor growth, whilst information from human tumors is also required.