Exercise for Lung Cancer

(ENHANCE Trial)

Overseen By Christina M Dieli-Conwright, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Dana-Farber Cancer Institute

Must be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Unstable comorbidities, Second malignancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different types of exercise affect people with advanced lung cancer who are receiving immune checkpoint inhibitors, a type of cancer therapy. Participants will engage in either high-intensity interval training (short bursts of vigorous exercise) or moderate-intensity continuous training (steady-paced exercise) on a stationary bike. The researchers aim to determine if one type of exercise offers more benefits than the other. This trial targets individuals with advanced non-small cell lung cancer who currently engage in minimal exercise and have a doctor's approval for physical activity. As an unphased trial, it provides a unique opportunity to contribute to understanding how exercise can enhance cancer treatment outcomes.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must have been receiving anti-PD-1 or anti-PD-L1 antibodies for at least one month and plan to continue them for at least 12 weeks.

What prior data suggests that these exercise programs are safe for individuals with advanced lung cancer?

Research has shown that High-Intensity Interval Training (HIIT) is safe and well-tolerated for people with cancer. One study found that HIIT helped lung cancer patients experience fewer lung problems after surgery, with a low risk of side effects while improving health. Another review of several studies confirmed that HIIT improved fitness in cancer patients with minimal negative effects.

For Moderate-Intensity Continuous Training (MICT), studies have shown it improves fitness and quality of life in lung cancer patients. Specifically, one study found that exercise programs like MICT were safe and beneficial for overall health. Both HIIT and MICT have shown promise in enhancing physical health with minimal risk, making them good options for those considering joining exercise-based clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these exercise protocols for lung cancer because they explore how different intensities of exercise can impact patients' health. High-Intensity Interval Training (HIIT) uses short bursts of vigorous exercise followed by recovery periods, which may improve cardiovascular fitness and overall endurance more efficiently than traditional methods. Moderate-Intensity Continuous Training (MICT), on the other hand, provides a steady exercise approach that balances intensity and duration, potentially benefiting those who prefer a less intense but consistent workout. Unlike conventional treatments that focus on medication or surgery, these exercise protocols aim to enhance quality of life and physical performance, offering a complementary approach to existing care.

What evidence suggests that this trial's exercise programs could be effective for lung cancer?

This trial will compare High-Intensity Interval Training (HIIT) and Moderate-Intensity Continuous Training (MICT) for lung cancer patients. Studies have shown that HIIT can significantly enhance lung function in these individuals. Specifically, research indicates that HIIT increases both VO2peak, which measures the body's oxygen usage, and FEV1, which measures the volume of air exhaled. Additionally, patients who participated in HIIT reported feeling better after 12 weeks. Meanwhile, MICT has effectively reduced cancer-related fatigue and improved overall quality of life for lung cancer patients. Both exercise types show promise in enhancing well-being and fitness levels for these patients. ^{1 2 4 5 6}

Who Is on the Research Team?

Christina Dieli-Conwright, PhD, MPH

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

The INHALE Trial is for adults over 18 with advanced lung cancer who are on single-agent anti-PD-1 or anti-PD-L1 immunotherapy and can exercise safely. They should do less than 60 minutes of moderate-to-vigorous exercise weekly, not be on other systemic treatments like chemo, and must understand English.

Inclusion Criteria

You have been doing less than 60 minutes of moderate-to-intense exercise per week for the past month.

I have been diagnosed with metastatic non-small cell lung cancer.

I do not have any health conditions that get worse with exercise.

Exclusion Criteria

I do not have another cancer that needs treatment at the same time as this study.

I am not on any other systemic treatments for NSCLC besides anti-PD-1/PD-L1.

You have been doing more than 60 minutes of moderate-to-vigorous exercise each week for the past month. This study is for people who don't exercise much, so if you've been doing more exercise, it might affect the study results.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 12 weeks of exercise training at different intensities while receiving immune checkpoint inhibitors

12 weeks

3 sessions per week (virtually supervised)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Open-label extension (optional)

Participants in the Usual Care group may opt into the exercise program after the initial 12 weeks

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• High-Intensity Interval Training
• Moderate-Intensity Continuous Training

Trial Overview

This study tests if a home-based, virtually supervised 12-week exercise program is workable and beneficial for lung cancer patients on immunotherapy. It compares high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), and usual care.

How Is the Trial Designed?

Group I: Moderate-Intensity Continuous Training (MICT) Experimental Treatment 1 Intervention

The MICT group will perform an aerobic exercise at a continuous intensity in each session on a stationary bike. Similar to HIIT, the intensity will be progressed (47.5-60%). The total work of MICT is equalized with HIIT for training volume and frequency to compare the differences exerted from different intensities and energy expenditure.

Group II: High-Intensity Interval Training (HIIT) Experimental Treatment 1 Intervention

Patients in the HIIT group will perform alternating vigorous-intensity and recovery aerobic exercise intervals on a provided home stationary bike. The HIIT protocol consists of alternating a high-intensity exercise phase (1 min at 65-90% of workload corresponding to VO2peak) and a recovery phase (1 min at 30%), and the high-intensity and recovery intervals will be repeated 5-10 times in each session.

Group III: Usual Care (UC) Active Control 1 Intervention

Participants will be asked to maintain their baseline exercise behavior and will be offered to participate in the HIIT exercise program upon the completion of post-intervention assessments after the initial 12 weeks.

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A randomized trial involving 151 patients with operable lung cancer found that preoperative high-intensity interval training (HIIT) rehabilitation did not lead to significant improvements in pulmonary function or aerobic capacity one year after surgery.

Both the rehabilitation group and the usual care group showed similar reductions in peak oxygen uptake and peak work rate, indicating that the short-term HIIT intervention did not enhance long-term postoperative outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term preoperative exercise therapy does not improve long-term outcome after lung cancer surgery: a randomized controlled study. Karenovics, W., Licker, M., Ellenberger, C., et al.[2022]

Maximal-intensity aerobic interval training (MAIT) significantly improved maximal oxygen uptake (O2max) by 31% in patients with acute coronary syndrome, compared to a 17% increase with high-intensity aerobic interval training (HAIT), indicating that MAIT may be more effective for enhancing cardiovascular fitness.

Both MAIT and HAIT were found to be safe, with no major cardiovascular or musculoskeletal complications reported during the 6-week training period, suggesting their suitability for cardiac rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect and Safety of Aerobic Interval Training According to Exercise Intensity in Acute Coronary Syndrome. Kim, C., Choi, HE.[2021]

High-intensity interval training (HIIT) significantly improves cardiorespiratory fitness (measured as peak V̇O2) in cancer patients and survivors compared to usual care, with a mean difference of 2.11 ml kg-1 min-1.

HIIT shows similar effectiveness to moderate-intensity continuous training (MICT) in improving peak V̇O2, while also demonstrating better adherence rates (71.2% to 95.6%) and no serious adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-intensity interval training improves cardiorespiratory fitness in cancer patients and survivors: A meta-analysis. Wallen, MP., Hennessy, D., Brown, S., et al.[2021]

In a study involving 240 women undergoing chemotherapy for breast cancer, resistance and high-intensity interval training (RT-HIIT) significantly reduced cancer-related fatigue (CRF) compared to usual care, improving daily life and physical symptoms.

Both RT-HIIT and moderate-intensity aerobic training (AT-HIIT) enhanced health-related quality of life, with RT-HIIT also reducing overall symptom burden, highlighting the importance of structured exercise in cancer rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding high-intensity interval training to conventional training modalities: optimizing health-related outcomes during chemotherapy for breast cancer: the OptiTrain randomized controlled trial. Mijwel, S., Backman, M., Bolam, KA., et al.[2019]

High-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) both improved aerobic capacity (VO2peak) and waist circumference in breast cancer survivors over a 12-week program, but there were no significant differences between the two training methods.

While HIIT led to increases in minute ventilation and peak workload, it did not result in a greater improvement in VO2peak compared to MICT, suggesting that both training intensities are beneficial for previously trained breast cancer survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Additional cardiovascular fitness when progressing from moderate- to high-intensity exercise training in previously trained breast cancer survivors. Bell, RA., Baldi, JC., Jones, LM.[2021]

Exercise training is safe and effective for improving health outcomes in lung cancer patients, particularly those with non-small cell lung cancer (NSCLC), and can be beneficial at various stages of the disease, including before and after surgery.

The review highlights the need for further research on exercise's role in lung cancer care, including its effects on patients with bone metastases and its potential to suppress tumor growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise training as part of lung cancer therapy. Cavalheri, V., Granger, CL.[2021]

Exercise interventions for lung cancer patients significantly reduce post-operative complications and improve exercise capacity, based on a systematic review of 30 studies involving a total of 6440 participants.

While exercise showed benefits in pre- and post-operative settings, health-related quality of life improvements were mostly non-significant, indicating a need for further high-quality research, especially in non-surgical populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise across the Lung Cancer Care Continuum: An Overview of Systematic Reviews. Edbrooke, L., Bowman, A., Granger, CL., et al.[2023]

This study will evaluate the effectiveness of high-intensity interval training (HIIT) compared to moderate-intensity continuous training (MICT) in improving aerobic capacity in dogs, involving 30 dogs over a 12-week training period.

The research aims to measure various physiological parameters, including maximal speed and lactate threshold, to determine if HIIT provides superior benefits in enhancing physical performance in dogs compared to MICT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of high-intensity interval training compared with moderate-intensity continuous training on maximal aerobic potency in dogs: Trial protocol for a randomised controlled clinical study. Orozco, SC., Arias, MP., Carvajal, PA., et al.[2023]

Exercise training is a safe and feasible adjunct therapy for patients with operable lung cancer, both before and after surgery, helping to improve their ability to tolerate exercise and potentially enhancing their quality of life.

For patients with inoperable lung cancer, while more research is needed, preliminary evidence indicates that carefully prescribed exercise training could also be beneficial and should be considered in their overall treatment plan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise therapy across the lung cancer continuum. Jones, LW., Eves, ND., Waner, E., et al.[2021]

In a study of 81 heart disease patients with very high cardiovascular risk, both moderate and high-intensity interval training (MIIT and HIIT) were found to be safe, with no adverse outcomes reported during the training.

While there were no statistically significant differences in overall exercise improvements between the training types, the HIIT group showed a trend towards greater improvements in exercise tolerance, suggesting it may be more effective than continuous moderate intensity training (MICT).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and improvement in exercise tolerance with interval training vs moderate-intensity continuous training in heart disease patient of very high cardiovascular risk. Pineda-García, AD., Lara-Vargas, JA., Ku-González, A., et al.[2022]

High-intensity interval training (HIIT) is as effective, if not more so, than traditional moderate-intensity continuous training (MICT) for patients with cardiovascular disease, based on a systematic review of 23 studies involving 1117 participants.

The safety profile of HIIT in cardiac rehabilitation is promising, with only one major cardiovascular adverse event reported per 17,083 training sessions, indicating that HIIT can be safely implemented in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Intensity Interval Training for Patients With Cardiovascular Disease-Is It Safe? A Systematic Review. Wewege, MA., Ahn, D., Yu, J., et al.[2021]

High-intensity interval training (HIIT) is safe and feasible for a small group of pediatric cancer patients aged 6 to 18, with 11 out of 212 eligible patients successfully completing the exercise without serious adverse events.

During HIIT, patients achieved high heart rates (up to 90% of their maximum) and significant increases in blood lactate levels, indicating that while HIIT can be performed, individualized exercise protocols are necessary to accommodate the varying health conditions of childhood cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Bout of High-Intensity Interval Training (HIIT) in Children and Adolescents during Acute Cancer Treatment-A Pilot Feasibility Study. Kesting, S., Weeber, P., Schönfelder, M., et al.[2023]

A quasi-experimental trial showed that high-intensity interval training combined with team empowerment education significantly improved dyspnea, exercise capacity, exercise self-efficacy, anxiety, and depression in lung cancer patients undergoing surgery.

The intervention was found to be safe and feasible, suggesting it can effectively manage perioperative symptoms, although it did not impact the duration of thoracic drainage or total hospital stay.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Preoperative High-Intensity Interval Training Combined With Team Empowerment Education in Lung Cancer Patients With Surgery: A Quasi-experimental Trial. Lu, HB., Wang, YQ., Liu, X., et al.[2023]

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