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High Intensity Aerobic Exercise Training and Immune Cell Mobilization in Patients With Lung Cancer (HI AIM) (HIAIM)

Primary Purpose

Cancer, Cancer of Lung

Status
Recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Exercise intervention
Standard oncological treatments
Sponsored by
Herlev Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Metastatic non-small cell lung cancer
  • Measurable disease according to RECIST 1.1
  • Age ≥ 18 years
  • Treatment with immune checkpoint inhibitors, checkpoint inhibitors combined with chemotherapy or oncological surveillance
  • Eastern Cooperative Oncology Group (ECOG) performance status score (PS) ≤2
  • Preferably metastasis suitable for biopsy

  • Normal marrow function as defined below:

    • White blood cell count (WBC) ≥ 2 x 10⁹/L
    • Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L
    • Hemoglobin ≥ 6.0 mmol/l
    • Platelet count ≥ 100 x 10⁹/L
    • In case, a patient's bone marrow values fall slightly below the described values, the treatment responsible doctor will be consulted. The general health and the ability to proceed with the treatment will be considered.
  • Ability to speak and read Danish
  • Willingness to give informed consent for participation in the study

Exclusion Criteria:

  • Any physical condition that hinder the execution of physical exercise, as assessed by the referring oncologist and by a physiotherapist
  • Severe dyspnea that hinder the execution of high intensity aerobic exercise training, as assessed by the referring oncologist
  • Symptomatic brain metastases
  • Dementia, psychotic disorders, or other cognitive diseases or conditions that hinder participation in a clinical exercise-based trial, as assessed by the referring oncologist
  • Unstable medical disease or history of serious or concurrent illness; any medical condition that might be aggravated by exercise training or that cannot be controlled, including, but not restricted to congestive heart failure (NYHA class III-IV), unstable angina pectoris, implantable cardioverter defibrillator (ICD), or myocardial infarction within 6 months
  • A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications. Inhaled or topical steroids and adrenal replacement doses ≤ 10 mg daily prednisone equivalents are permitted
  • Use of beta blockers
  • Any systemic infections within the last 4 weeks
  • Patients who receives chemotherapy as monotherapy

  • In patients with documented bone metastases; patients with:

    • A bone metastatic burden or location that poses a risk of injury in the performance of exercise training, as assessed by the referring oncologist

Sites / Locations

  • Herlev HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Intervention group

Control group

Arm Description

Participants in the intervention group will receive a 6-weeks exercise-based intervention with supervised and group-based exercise training three times a week at the hospital setting. Each training session will consist of intermediate and high intensity interval training. The exercise-based intervention will be combined with standard oncological treatments; checkpoint inhibitors, checkpoint inhibitors combined with chemotherapy or oncological surveillance. Additional monitoring of patient will include physical tests, questionnaires and blood samples.

Participants in the control group will receive standard oncological treatments; immune checkpoint inhibitors, checkpoint inhibitors combined with chemotherapy or oncological surveillance. Additional monitoring of patient will include physical tests, questionnaires and blood samples.

Outcomes

Primary Outcome Measures

Circulating NK cells
Flow cytometry will be used to analyse and determine amount of circulating NK cells. The analysis will focus on absolute counts of NK cells, but also surface expression of various surface markers of interest.

Secondary Outcome Measures

Maximal aerobic capacity
Measure difference in maximal aerobic capacity before and after exercise intervention.
Circulating T cells and B cells.
Flow cytometry will be used to analyse and determine amount of circulating NK cells. The analysis will focus on absolute counts of NK cells, but also surface expression of various surface markers of interest eg. PD-1.
Circulating serum markers of inflammation
We aim to establish a panel of serum markers that reflect the effect of exercise training. This will be establish through big panel analysis of inflammatory markers using luminex assays. We will compare serum from blood samples taken before and after exercise training.
Overall survival
Overall Survival (OS), defined as time from treatment initiation to death, will be described with use of Kaplan Meier curve.
Progression free survival (PFS)
Defined as the time from the date of randomization until the date of progressive disease (PD). This is determined by investigator assessment of objective radiographic disease assessments per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) and immune RECIST (iRECIST)

Full Information

First Posted
February 5, 2020
Last Updated
March 16, 2022
Sponsor
Herlev Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04263467
Brief Title
High Intensity Aerobic Exercise Training and Immune Cell Mobilization in Patients With Lung Cancer (HI AIM)
Acronym
HIAIM
Official Title
High Intensity Aerobic Exercise Training and Immune Cell Mobilization in Patients With Lung Cancer (HI AIM)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 17, 2020 (Actual)
Primary Completion Date
October 1, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Herlev Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to investigate if high-intensive training can mobilize and activate the immune system, and thereby enhance the effect of the conventional treatment of lung cancer patients. An important aspect of this study will investigate if the presence of various proteins and cells in blood and tumor biopsies can verify or predict the effect of the high-intensive training. In this clinical trial, patients with lung cancer will combine their conventional therapy with a six-week exercise program.
Detailed Description
Research has shown that exercise training has several beneficial effects in cancer patients and survivors both during and after anti-cancer treatment, including improved physical function, reduction of symptoms, reduction of side effects and improved quality of life (QoL). In addition, a physical active lifestyle is associated with reduced risk of some cancers. Recent data in mouse models have shown that tumor-bearing mice randomized to a voluntary wheel running group showed over 60% reduction in tumor incidence and progression in several tumor models. Moreover, the mouse data clearly showed homing of T and natural killer (NK) cells to tumors in an exercise dependent manner, underscoring that exercise may render patients more prone to respond to therapy. However, most of the underlying biological mechanisms leading to the documented beneficial effects of physical exercise in relation to cancer are yet unknown, but exercise-mediated changes in hormone levels, inflammation and immune cell function are thought to play a key role. Included participants will be randomized 1:1 to an intervention group and a control group. Participants in the intervention group will receive a six-weeks exercise-based intervention with supervised and group-based exercise training three times a week at the hospital setting. Each training session will consist of intermediate and high intensity interval training. The exercise-based intervention will be combined with standard oncological treatments; checkpoint inhibitors, checkpoint inhibitors combined with chemotherapy or oncological surveillance. Participants in the control group will still receive standard oncological treatments; immune checkpoint inhibitors, checkpoint inhibitors combined with chemotherapy or oncological surveillance.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer, Cancer of Lung

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention group
Arm Type
Experimental
Arm Description
Participants in the intervention group will receive a 6-weeks exercise-based intervention with supervised and group-based exercise training three times a week at the hospital setting. Each training session will consist of intermediate and high intensity interval training. The exercise-based intervention will be combined with standard oncological treatments; checkpoint inhibitors, checkpoint inhibitors combined with chemotherapy or oncological surveillance. Additional monitoring of patient will include physical tests, questionnaires and blood samples.
Arm Title
Control group
Arm Type
Experimental
Arm Description
Participants in the control group will receive standard oncological treatments; immune checkpoint inhibitors, checkpoint inhibitors combined with chemotherapy or oncological surveillance. Additional monitoring of patient will include physical tests, questionnaires and blood samples.
Intervention Type
Other
Intervention Name(s)
Exercise intervention
Intervention Description
The exercise intervention will consist a intermediate to high aerobic exercise training program.
Intervention Type
Other
Intervention Name(s)
Standard oncological treatments
Intervention Description
Standard oncological treatments
Primary Outcome Measure Information:
Title
Circulating NK cells
Description
Flow cytometry will be used to analyse and determine amount of circulating NK cells. The analysis will focus on absolute counts of NK cells, but also surface expression of various surface markers of interest.
Time Frame
0 - 36 months
Secondary Outcome Measure Information:
Title
Maximal aerobic capacity
Description
Measure difference in maximal aerobic capacity before and after exercise intervention.
Time Frame
0 - 36 months
Title
Circulating T cells and B cells.
Description
Flow cytometry will be used to analyse and determine amount of circulating NK cells. The analysis will focus on absolute counts of NK cells, but also surface expression of various surface markers of interest eg. PD-1.
Time Frame
0 - 36 months
Title
Circulating serum markers of inflammation
Description
We aim to establish a panel of serum markers that reflect the effect of exercise training. This will be establish through big panel analysis of inflammatory markers using luminex assays. We will compare serum from blood samples taken before and after exercise training.
Time Frame
0 - 36 months
Title
Overall survival
Description
Overall Survival (OS), defined as time from treatment initiation to death, will be described with use of Kaplan Meier curve.
Time Frame
0 - 36 months
Title
Progression free survival (PFS)
Description
Defined as the time from the date of randomization until the date of progressive disease (PD). This is determined by investigator assessment of objective radiographic disease assessments per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) and immune RECIST (iRECIST)
Time Frame
0 - 36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Metastatic non-small cell lung cancer Measurable disease according to RECIST 1.1 Age ≥ 18 years Treatment with immune checkpoint inhibitors, checkpoint inhibitors combined with chemotherapy or oncological surveillance Eastern Cooperative Oncology Group (ECOG) performance status score (PS) ≤2 Preferably metastasis suitable for biopsy Normal marrow function as defined below: White blood cell count (WBC) ≥ 2 x 10⁹/L Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L Hemoglobin ≥ 6.0 mmol/l Platelet count ≥ 100 x 10⁹/L In case, a patient's bone marrow values fall slightly below the described values, the treatment responsible doctor will be consulted. The general health and the ability to proceed with the treatment will be considered. Ability to speak and read Danish Willingness to give informed consent for participation in the study Exclusion Criteria: Any physical condition that hinder the execution of physical exercise, as assessed by the referring oncologist and by a physiotherapist Severe dyspnea that hinder the execution of high intensity aerobic exercise training, as assessed by the referring oncologist Symptomatic brain metastases Dementia, psychotic disorders, or other cognitive diseases or conditions that hinder participation in a clinical exercise-based trial, as assessed by the referring oncologist Unstable medical disease or history of serious or concurrent illness; any medical condition that might be aggravated by exercise training or that cannot be controlled, including, but not restricted to congestive heart failure (NYHA class III-IV), unstable angina pectoris, implantable cardioverter defibrillator (ICD), or myocardial infarction within 6 months A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications. Inhaled or topical steroids and adrenal replacement doses ≤ 10 mg daily prednisone equivalents are permitted Use of beta blockers Any systemic infections within the last 4 weeks Patients who receives chemotherapy as monotherapy In patients with documented bone metastases; patients with: A bone metastatic burden or location that poses a risk of injury in the performance of exercise training, as assessed by the referring oncologist
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Per thor Straten, Professor
Phone
0045 38683868
Email
per.thor.straten@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Gitte Holmen Olofsson, PhD
Phone
0045 38683868
Email
gitte.holmen.olofsson@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Per thor Straten, Professor
Organizational Affiliation
CCIT
Official's Role
Study Director
Facility Information:
Facility Name
Herlev Hospital
City
Herlev
ZIP/Postal Code
2730
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Per thor Straten, Prof
Phone
0045 38683868
Email
per.thor.straten@regionh.dk
First Name & Middle Initial & Last Name & Degree
Gitte Holmen Olofsson, PhD
Phone
0045 38683868
Email
gitte.holmen.olofsson@regionh.dk

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
The individual participant data (IPD) sharing plan will be consider at the end of the trial.
Citations:
PubMed Identifier
35247994
Citation
Holmen Olofsson G, Mikkelsen MK, Ragle AM, Christiansen AB, Olsen AP, Heide-Ottosen L, Horsted CB, Pedersen CMS, Engell-Noerregaard L, Lorentzen T, Persson GF, Vinther A, Nielsen DL, Thor Straten P. High Intensity Aerobic exercise training and Immune cell Mobilization in patients with lung cancer (HI AIM)-a randomized controlled trial. BMC Cancer. 2022 Mar 5;22(1):246. doi: 10.1186/s12885-022-09349-y.
Results Reference
derived

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High Intensity Aerobic Exercise Training and Immune Cell Mobilization in Patients With Lung Cancer (HI AIM)

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