Exercise for Lung Cancer

(ENHANCE Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Christina Dieli-Conwright, PhD, MPH

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Dana-Farber Cancer Institute

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

Disqualifiers: Unstable comorbidities, Second malignancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing two types of exercise programs for people with advanced lung cancer who are receiving a specific cancer treatment. One program involves short bursts of intense exercise, while the other involves steady, moderate exercise. The goal is to see if these exercises can improve health and reduce side effects from their treatment.

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 data supports the effectiveness of the treatment High-Intensity Interval Training for lung cancer patients?

High-Intensity Interval Training (HIIT) has been shown to improve cardiorespiratory fitness in cancer patients and survivors, which is important for overall health and recovery. Additionally, HIIT is associated with the largest improvements in aerobic capacity compared to moderate-intensity exercise, which can be beneficial for lung cancer patients undergoing surgery. ^{1 2 3 4 5}

Is high-intensity interval training (HIIT) safe for humans?

Research shows that high-intensity interval training (HIIT) is generally safe for humans, including those with heart disease and children undergoing cancer treatment, with a low rate of major adverse events reported. ^{6 7 8 9 10}

How is the exercise treatment for lung cancer different from other treatments?

This treatment is unique because it uses exercise, specifically High-Intensity Interval Training (HIIT) and Moderate-Intensity Continuous Training (MCT), to improve lung cancer patients' fitness and quality of life, which is different from traditional drug-based treatments. Exercise is shown to be safe and effective in enhancing outcomes for lung cancer patients, both before and after surgery, and may help in managing the disease alongside other therapies. ^{1 5 11 12 13}

Research Team

Christina Dieli-Conwright, PhD, MPH

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• High-Intensity Interval Training (Behavioral Intervention)
• Moderate-Intensity Continuous Training (Behavioral Intervention)

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.

Participant Groups

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+

Dr. Benjamin L. Ebert

Dana-Farber Cancer Institute

Chief Executive Officer

MD from Harvard Medical School, PhD from Oxford University

Dr. Craig A. Bunnell

Dana-Farber Cancer Institute

Chief Medical Officer since 2012

MD from Harvard Medical School, MPH from Harvard School of Public Health, MBA from MIT Sloan School of Management

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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]

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]

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]

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]

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 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]

References

1. United States 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. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Additional cardiovascular fitness when progressing from moderate- to high-intensity exercise training in previously trained breast cancer survivors. [2021]

3. England pubmed.ncbi.nlm.nih.gov

High-intensity interval training improves cardiorespiratory fitness in cancer patients and survivors: A meta-analysis. [2021]

4. Netherlands 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. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Short-term preoperative exercise therapy does not improve long-term outcome after lung cancer surgery: a randomized controlled study. [2022]

6. Mexico 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. [2022]

7. England pubmed.ncbi.nlm.nih.gov

High-Intensity Interval Training for Patients With Cardiovascular Disease-Is It Safe? A Systematic Review. [2021]

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

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

9. Switzerland 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. [2023]

10. United States 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. [2023]

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

Exercise therapy across the lung cancer continuum. [2021]

12. Australia pubmed.ncbi.nlm.nih.gov

Exercise training as part of lung cancer therapy. [2021]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Exercise across the Lung Cancer Care Continuum: An Overview of Systematic Reviews. [2023]