The Impact of Exercise on the Tumor Microenvironment in Patients With Lung Cancer

NCT07216209 | Recruiting DMC

• 1 other identifier: STUDY00005883
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

There is increased interest and knowledge about the lung cancer tumor microenvironment (TME). Investigators hypothesize that patients with better baseline physiologic health will have better post-operative outcomes and that strenuous exercise will alter the TME and genetic make-up of the tumor, improving the tumor immune response. Investigators aim to identify the peri-operative and clinical outcomes that differ based on pre-operative VO2max, HRV and resting heart rate following resection of early-stage lung cancer. The physiologic states that are individual and measurable with wearable devices include but are not limited to VO2max, heart rate variability (HRV), and average resting heart rate. Investgators hypothesize that a patient's pre-operative physiologic function with higher VO2max, HRV and lower resting heart rate will be associated with improved peri-operative and post-operative outcomes. Second, investigators will compare alterations in TME based on targeted pre-operative exercise (60-80% of their VO2 max for 75min/week x2 weeks) compared to normal activity adults following resection of early-stage lung cancer. Investigators hypothesize that strenuous exercise in the pre-operative period will impact the TME by increasing levels of cytokines.

Conditions

Lung Cancer - Non Small Cell

Keywords

exercise; tumor microenvironment; lung cancer

Outcome Measures

Primary Outcomes (1)

• Tumor Microenvironment

  Lung cancer specimens will be collected from all patients at the time of surgery. Investigators will perform real-time PCR to identify levels of PDL-1

  Baseline, Perioperative, up to 24 months

Secondary Outcomes (1)

• Recurrence and Survival

  Baseline, Perioperative, up to 24 months

Study Arms (1)

Exercise arm

EXPERIMENTAL

All patients will be offered a lab exercise regimen. For completion of Aim 2, only three or four visits are necessary, amounting to approximately 4 hours of the patient's time. The initial visit will be for pre-exercise screening. If the patient is deemed healthy enough to participate, an exercise test to determine the ventilatory threshold of the participant will be conducted and the VO2 determined. In the subsequent visits, the patient will perform exercise for 30 minutes at 15% above the volunteer's ventilatory threshold. Ideally, the patients will be able to complete a minimum of three sessions prior to surgery.

Behavioral: EXERCISE TRAINING WITH OR WITHOUT MEDICATION

Interventions

EXERCISE TRAINING WITH OR WITHOUT MEDICATION BEHAVIORAL

All patients will be offered a lab exercise regimen. For completion of Aim 2, only three or four visits are necessary, amounting to approximately 4 hours of the patient's time. The initial visit will be for pre-exercise screening. If the patient is deemed healthy enough to participate, an exercise test to determine the ventilatory threshold of the participant will be conducted and the VO2 determined. In the subsequent visits, the patient will perform exercise for 30 minutes at 15% above the volunteer's ventilatory threshold. Ideally, the patients will be able to complete a minimum of three sessions prior to surgery.

Exercise arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• lung cancer
• low risk for submaximal exercise testing in accordance with the risk stratification guidelines published by the American Heart Association and the American College of Sports Medicine (AHA/ACSM criteria).

You may not qualify if:

• younger than 18 years of age
• select a condition on the ACSM-AHA pre-exercise screening questionnaire indicating that physician approval is required prior to exercise
• body mass index of \>30 kg/m2
• waist girth of \>102cm for men and \>88cm for women
• have chronic/debilitating arthritis
• have been bedridden in the past three months
• have common illness (i.e. colds) within the past 6-weeks
• HIV
• hepatitis
• history of stroke
• major affective disorder
• autoimmune disease
• pregnancy or are breast-feeding
• history of severe anaphylactic reaction to an allergen
• present with more than one of the following CVD risk factors: family history of myocardial infarction, coronary revascularization, or sudden death before 55 years of age in father or other male first-degree relative or before 65 years of age in mother or other female first-degree relative

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (1)

University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

RECRUITING

Related Publications (8)

• Tan Z, Xue H, Sun Y, Zhang C, Song Y, Qi Y. The Role of Tumor Inflammatory Microenvironment in Lung Cancer. Front Pharmacol. 2021 May 17;12:688625. doi: 10.3389/fphar.2021.688625. eCollection 2021.

  PMID: 34079469 BACKGROUND

• Ito M, Ishii G, Nagai K, Maeda R, Nakano Y, Ochiai A. Prognostic impact of cancer-associated stromal cells in patients with stage I lung adenocarcinoma. Chest. 2012 Jul;142(1):151-158. doi: 10.1378/chest.11-2458.

  PMID: 22302300 BACKGROUND

• Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014 Nov 27;515(7528):563-7. doi: 10.1038/nature14011.

  PMID: 25428504 BACKGROUND

• Zhang L, Chen Y, Wang H, Xu Z, Wang Y, Li S, Liu J, Chen Y, Luo H, Wu L, Yang Y, Zhang H, Peng H. Massive PD-L1 and CD8 double positive TILs characterize an immunosuppressive microenvironment with high mutational burden in lung cancer. J Immunother Cancer. 2021 Jun;9(6):e002356. doi: 10.1136/jitc-2021-002356.

  PMID: 34140315 BACKGROUND

• Rosero ID, Ramirez-Velez R, Lucia A, Martinez-Velilla N, Santos-Lozano A, Valenzuela PL, Morilla I, Izquierdo M. Systematic Review and Meta-Analysis of Randomized, Controlled Trials on Preoperative Physical Exercise Interventions in Patients with Non-Small-Cell Lung Cancer. Cancers (Basel). 2019 Jul 5;11(7):944. doi: 10.3390/cancers11070944.

  PMID: 31284372 BACKGROUND

• Simpson RJ, Campbell JP, Gleeson M, Kruger K, Nieman DC, Pyne DB, Turner JE, Walsh NP. Can exercise affect immune function to increase susceptibility to infection? Exerc Immunol Rev. 2020;26:8-22.

  PMID: 32139352 BACKGROUND

• Puchelle E, Zahm JM, Tournier JM, Coraux C. Airway epithelial repair, regeneration, and remodeling after injury in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2006 Nov;3(8):726-33. doi: 10.1513/pats.200605-126SF.

  PMID: 17065381 BACKGROUND

• Wang J, Linxweiler M, Yang W, Chan TA, Morris LGT. Immunomodulatory and immunotherapeutic implications of tobacco smoking in squamous cell carcinomas and normal airway epithelium. Oncotarget. 2019 Jun 11;10(39):3835-3839. doi: 10.18632/oncotarget.26982. eCollection 2019 Jun 11.

  PMID: 31231463 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Motor Activity; Lung Neoplasms

Interventions

Exercise; Dosage Forms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques

Study Officials

• Stephanie Worrell, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephanie Worrell, MD

CONTACT

5206267806; sworrell@arizona.edu

Melissa Landau

CONTACT

5206267806; mlandau@surgery.arizona.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2024
• First Posted: October 14, 2025
• Study Start: January 13, 2026
• Primary Completion (Estimated): January 15, 2030
• Study Completion (Estimated): January 15, 2030
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)