Feasibility and Preliminary Efficacy of Exercise During Immunotherapy in Patients With Lung Cancer: The INHALE Trial (INHALE)

• ClinicalTrials.gov Identifier: NCT06026111
• Recruitment Status: Recruiting
• First Posted: September 6, 2023
• Last Update Posted: February 21, 2024
• Sponsor: Dana-Farber Cancer Institute
• Information provided by (Responsible Party): Christina Dieli-Conwright, PhD, Dana-Farber Cancer Institute

Study Description

Brief Summary:

The purpose of this study is to determine whether a 12-week, home-based, virtually supervised exercise intervention is feasible and improves various health outcomes among individuals with advanced lung cancer receiving immunotherapy.

The names of the study interventions involved in this study are:

• High-intensity interval training (HIIT) (Home-based, virtually supervised, high intensity training in an interval fashion)
• Moderate-intensity continuous training (MICT) (Home-based, virtually supervised, moderate intensity in a continuous fashion)
• Usual care (UC)

Condition or disease	Intervention/treatment	Phase
Advanced Lung Cancer	Behavioral: High-Intensity Interval Training; Behavioral: Moderate-Intensity Continuous Training	Not Applicable

Detailed Description:

This single-center, two-armed, pilot randomized controlled research study will assess feasibility and compare immune activities, cardiorespiratory fitness, physical function, and immunotherapy-related adverse events, and patient-reported outcomes between three groups - high-intensity exercise, moderate-intensity exercise, and usual care.

Participants in this study will be randomly assigned to one of three groups: Group A High-intensity interval training (HIIT), Group B Moderate-intensity continuous training (MICT), or Group C Usual Care (UC). The HIIT and the MICT groups will receive virtually (Zoom) supervised home-based exercise training three sessions per week for 12 weeks. Randomization means that a participant is placed into a study group by chance.

The research study procedures include screening for eligibility and study treatment including extensive evaluations of fitness and physical health, blood tests, and questionnaires/surveys.

Participation in this research study is expected to last for up to 12 weeks.

It is expected that about 30 people will take part in this research study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Feasibility and Preliminary Efficacy of Exercise During Immunotherapy in Patients With Lung Cancer: The INHALE Trial
• Actual Study Start Date: December 8, 2023
• Estimated Primary Completion Date: July 31, 2024
• Estimated Study Completion Date: April 30, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group A: High-Intensity Interval Training; 10 Participants will complete study procedures as follows: Baseline clinic visit with assessments.; 36 virtual sessions of exercise intervention, 3 x weekly.; Post-intervention clinic visit with assessments.	Behavioral: High-Intensity Interval Training; Home-based, virtually supervised, aerobic exercise intervention with trained exercise specialist. Exercise is high intensity in an interval fashion. Participants will be provided with home stationary bike, heart-rate monitor/watch, and automatic blood pressure cuff.
Experimental: Group B: Moderate-Intensity Continuous Training; 10 Participants will complete study procedures as follows: Baseline clinic visit with assessments.; 36 virtual sessions of exercise intervention, 3 x weekly.; Post-intervention clinic visit with assessments.	Behavioral: Moderate-Intensity Continuous Training; Home-based, virtually supervised, aerobic exercise intervention with trained exercise specialist. Exercise is moderate intensity in a continuous fashion. Participants will be provided with home stationary bike, heart-rate monitor/watch, and automatic blood pressure cuff.
No Intervention: Group C: Usual Care; 10 Participants will complete study procedures as follows: Post-intervention clinic visit with assessments.; 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.

Outcome Measures

Primary Outcome Measures :

1. Proportion of Participants completing the exercise intervention sessions [ Time Frame: Up to 14 weeks ]
   The primary outcome is feasibility and will be assessed by the proportion of enrolled participants completing the exercise intervention sessions with >/=70% completion considered feasible.

Secondary Outcome Measures :

1. Neutrophil-lymphocyte ratio (NLR) [ Time Frame: Baseline (Week 1) and post-intervention (Week 14) ]
   Neutrophil-lymphocyte ratio (NLR) will be assessed as a systemic immune marker as well as a prognostic marker of immunotherapy. Mononuclear lymphocyte phenotypes will be conducted in the Immune Assessment Laboratory. Immunofluorescence assays in whole blood will identify the counts of neutrophils and lymphocytes. Fasting blood will be taken in the morning following an overnight fast. Two 10.0 mL EDTA tubes will be collected and one spun for 10 minutes at 2860rpm within one hour of collection and 1.0mL of plasma will be transferred to a secondary tube to cryovials. Samples will be stored or shipped frozen at -70°C. Samples will be centrifuged, stored at -80°C, and batch-analyzed after post-intervention assessments.
2. Cardiopulmonary Fitness [ Time Frame: Baseline (Week 1) and post-intervention (Week 14) ]
   Cardiorespiratory fitness will be assessed as VO2peak by a graded maximal cycle exercise stress test. VO2peak is defined as the highest values of oxygen uptake averaged among every 15-second interval during the test. VO2peak will be reported in both relative (ml·kg-1·min-1) and absolute (L/min) terms.
3. Muscular Strength [ Time Frame: Baseline (Week 1) and post-intervention (Week 14) ]
   Muscular strength will be measured as 1-repetition maximum (RM) (i.e., the greatest resistance that can be moved through the full range of motion), which has been the standard for strength assessments. 1-RM values will be estimated from 10-RM using validated equations on 12 exercises including the ten exercises utilized in the prescription not performed on machines.
4. Short Physical Performance Battery [ Time Frame: Baseline (Week 1) and post-intervention (Week 14) ]
   Physical function will be assessed by the Short Physical Performance Battery (SPPB), which includes the following 3 lower extremity measures completed in the following order. Timed balance (seconds): Balance will be assessed under 3 conditions (side-by-side, semi-tandem, and tandem stands). Gait speed (seconds): Gait speed will be assessed over a 4-meter flat surface distance. The participant will be asked to complete 2 attempts of this test. Time will be recorded using an electronic timing system. Chair stand (seconds): Chair stand will be performed under 2 conditions: a) subjects will perform a single chair stand; b) subjects will be asked to perform 5 repeated chair stands as quickly as possible; time to completion will be recorded.
5. Patient Reported Outcomes - Health-related quality of life [ Time Frame: Baseline (Week 1) and post-intervention (Week 14) ]
   quality of life will be assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)-C30.
6. Patient Reported Outcomes - Lung-cancer related quality of life [ Time Frame: Baseline (Week 1) and post-intervention (Week 14) ]
   Lung-cancer related quality of life will be assessed by the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-Lung Cancer (EORTC-QLQ-LC)-29.
7. Patient Reported Outcomes - Immunotherapy Symptoms [ Time Frame: Baseline (Week 1) and post-intervention (Week 14) ]
   Immunotherapy symptoms will be assessed by the MD Anderson Symptom Inventory (MDASI) Immunotherapy early-phase trials (EPT).
8. Patient Reported Outcomes - Anxiety and Depression [ Time Frame: Baseline (Week 1) and post-intervention (Week 14) ]
   Anxiety and Depression will be assess using the Hospital Anxiety and Depression Scale (HADS). The HADS consists of 14 items, divided into two 7-item subscales (anxiety and depression). The respondent rates each item on a 4-point scale ranging from 0 (absence) to 3 (extreme presence) and the total score is out of 42 (21 per subscale).
9. Patient Reported Outcomes - Sleep Quality [ Time Frame: Baseline (Week 1) and post-intervention (Week 14) ]
   Sleep will be assessed using the Pittsburg Sleep Quality Index (PSQI).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age ≥18 years; due to the rarity of the disease in those <18 years, this age bracket will not be included.
• Histologically diagnosed with metastatic Non-small cell lung cancer (NSCLC).
• Having been receiving single-agent anti-PD-1 or anti-PD-L1 monoclonal antibodies for at least one month (e.g., pembrolizumab, nivolumab, atezolizumab, durvalumab, cemiplimab, and avelumab) with a plan to continue for at least 12 weeks prospectively at the time of recruitment.
• Not receiving other concurrent systemic treatment (e.g., chemotherapy or targeted therapy).
• Medical clearance to perform exercise intervention and testing by their treating oncologist.
• No uncontrolled medical conditions that could be exacerbated with exercise (e.g., uncontrolled hypertension or diabetes).
• Ability to communicate and complete written forms in English.
• Participate in less than or equal to 60 minutes of moderate-to-vigorous aerobic exercise per week over the past month.
• Ability to understand and the willingness to sign informed consent prior to any study-related procedures.
• Willing to travel to DFCI for necessary data collection.

Exclusion Criteria:

• Receiving other concurrent systemic treatment for NSCLC such as chemotherapy or targeted therapy. This study is to exclusively target patients receiving anti-PD-1/PD-L-1 where other treatments may impact the study outcomes of intervention feasibility and efficacies.
• Participate in more than 60 minutes of moderate-to-vigorous aerobic exercise per week over the past month. This study targets insufficiently active persons to assess the effect of the described exercise intervention, where additional exercise done regularly will contaminate the intervention outcomes.
• Unstable comorbidities that prevent participation in moderate-to-vigorous intensity exercise. Patients with unstable comorbidities may develop unexpected adverse events from exercise. For the purpose of patients' safety, as well as because part of this study involves remote, home-based exercise where close supervision is not possible, patients with unstable medical conditions are excluded.
• Subjects who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.
• Development of second malignancy (except for basal cell carcinoma or squamous cell carcinoma of the skin) that requires concurrent treatment, which would interfere with this study.

Contacts and Locations

Contacts

Contact: Christina Dieli-Conwright, MPH, PhD; 617-582-8321; ChristinaM_Dieli-Conwright@dfci.harvard.edu

Locations

United States, Massachusetts

Dana-Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

Contact: Christina Dieli-Conwright, MPH, PhD 617-582-8321 ChristinaM_Dieli-Conwright@dfci.harvard.edu

Principal Investigator: Christina Dieli-Conwright, MPH, PhD

Sponsors and Collaborators

Dana-Farber Cancer Institute

Investigators

• Principal Investigator: Christina Dieli-Conwright, MPH, PhD; Dana-Farber Cancer Institute

More Information

• Responsible Party: Christina Dieli-Conwright, PhD, Principle Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT06026111
• Other Study ID Numbers: 23-247
• First Posted: September 6, 2023
• Last Update Posted: February 21, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Christina Dieli-Conwright, PhD, Dana-Farber Cancer Institute:

Advanced Lung Cancer; Lung Cancer

Additional relevant MeSH terms:

Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases