EMBRACE: Exercise Intervention During Chemotherapy in Advanced Lung Cancer Patients

Sponsor

University Hospital Southampton NHS Foundation Trust (Other)

Overall Status

Unknown status

CT.gov ID

NCT03334071

Collaborator

Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust (Other)

100

Enrollment

Location

Arms

68.9

Anticipated Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Trial Phase: Pilot

Indication: Stage IIIB/IV NSCLC

Primary Objective: To assess the feasibility and tolerability of exercise training during palliative chemotherapy.

Secondary Objective: 1) To assess fitness levels in patients undergoing palliative chemotherapy, and to explore whether exercise training can prevent a reduction in fitness.

To determine the baseline fitness, as assessed by cardiopulmonary exercise testing (CPET), of a cohort of patients with stage IIIb/IV non small cell lung cancer who are about to initiate treatment with chemotherapy 3) To compare patients enrolled in the EMBRACE randomized controlled trial (RCT) with those who decline.

4)To investigate any relationship between baseline fitness and outcomes including therapy related complications, response, and survival in those patients who decline exercise training or are randomized to observation.

To assess the feasibility of the translation of in-hospital exercise training to home-based training during chemotherapy.
To document the effects of chemotherapy on cellular energetics and mitochondrial function.

Rationale: Chemotherapy has a detrimental effect on physical fitness, and this effect can be later reversed by training. The investigators wish to understand the mechanism of this detrimental effect, and investigate whether it can be prevented or attenuated by giving chemotherapy concurrently with exercise training.

Trial Design: Randomised controlled study (1:1) comparing chemotherapy alone, with chemotherapy plus exercise training. A subgroup of patients will have muscle biopsies. Patients who decline randomisation will be offered enrolment into an observational arm.

Sample size : 100 patients (to include 48 who will be randomised, and 52 in the observational arm).

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer Non Small Cell Lung Cancer Stage IIIB Non Small Cell Lung Cancer Metastatic	Behavioral: Exercise	N/A

Detailed Description

EMBRACE is a multi-centre pilot study for 100 patients with EGFR negative NSCLC undergoing first line platinum based chemotherapy. It is a prospective randomised (1:1) 2-arm controlled study. A nested mechanism study will be performed in a sub group of patients willing to have muscle biopsies.

Patients will be randomised to the exercise intervention or the control arm. All patients will undergo standard chemotherapy with gemcitabine and carboplatin (or equivalent) for 12 weeks. Patients randomised to the intervention arm will undergo concurrent exercise training during their 12 weeks of chemotherapy treatment. Patients randomised to the control arm will undergo chemotherapy only. During the 12 weeks of the study, assessments will be performed on all patients (including CPET tests and HRQL questionnaires). The exercise training sessions and study assessments will not affect timing of delivery of chemotherapy. Patients who decline randomisation will be offered entry into an observational study.

The follow-up phase will commence when patients have completed 12 weeks of chemotherapy, or sooner for patients who stop chemotherapy early due to progressive disease or toxicity. During the follow-up phase data will be for survival and to follow any AEs related to study procedures. AEs not related to study procedures will not require follow up. Ongoing chemotherapy after week 12 will be as per investigator and patient choice, and may include further induction cycles, maintenance chemotherapy, or observation.

In a subgroup of willing patients muscle biopsies will be performed at baseline, during chemotherapy, and after completion of chemotherapy.

TRIAL OUTCOME MEASURES

The primary outcome variables for this feasibility and tolerability study will be adherence to the exercise training program, and adverse events.

The secondary outcome variables will be response to chemotherapy, fitness levels as measured by Cardiopulmonary Exercise Testing (CPET), Time to get up and go test (TUG), grip strength, bioimpedance, CT measures of cancer cachexia, and Montreal score, cancer related symptoms, HRQL, and activity levels.

The exploratory outcome variables will be overall survival, toxicity, and biomarkers of stress and cellular energetics.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Exercise interventionExercise intervention

Masking:

Double (Investigator, Outcomes Assessor)

Masking Description:

Cardiopulmonary exercise testing assessor, outcome/toxicity assessor

Primary Purpose:

Treatment

Official Title:

Exercise regiMens Before and duRing Advanced Cancer thErapy: A Pilot Study to Investigate Improvements in Physical Fitness With Exercise Training Programme Before and During Chemotherapy in Advanced Lung Cancer Patients.

Actual Study Start Date :

Apr 4, 2014

Anticipated Primary Completion Date :

Dec 30, 2019

Anticipated Study Completion Date :

Dec 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Exercise Intervention Patients in the intervention arm will participate in a supervised in-hospital, exercise training program on a cycle ergometer before and during chemotherapy. At week 5-6 there will be a transition period of in-hospital to home-based exercise training (at this point we will perform the exercises that they will perform at home in the in-hospital environment to ensure that the patient understands the home-based exercise training programme) and then week 7-12 will be home-based exercise training only with telephone support.	Behavioral: Exercise High intensity interspersed with short periods of exercise at a moderate intensity (aerobic interval training). We will also include resistance training in each session. The supervised in-hospital exercise training sessions will last <1 hour, exercise training intensities will be individually tailored to each CPET. Exercise training will involve repeated exercise bouts of 3 minutes at a moderate exercise intensity (80%AT) followed by 2 minutes of exercise at a high intensity (50%Δ) for a predetermined amount of time. The home-based training programme will involve stair climbing (where possible) and brisk walking to achieve heart rates commensurate with those achieved during the in-hospital exercise training sessions.
No Intervention: Negative Control Patients in the control arm will not undergo an exercise training program.
No Intervention: Observational Patients who do not enrol in RCT will be enrolled in the observational arm

Arm

Intervention/Treatment

Active Comparator: Exercise Intervention

Patients in the intervention arm will participate in a supervised in-hospital, exercise training program on a cycle ergometer before and during chemotherapy. At week 5-6 there will be a transition period of in-hospital to home-based exercise training (at this point we will perform the exercises that they will perform at home in the in-hospital environment to ensure that the patient understands the home-based exercise training programme) and then week 7-12 will be home-based exercise training only with telephone support.

Behavioral: Exercise

High intensity interspersed with short periods of exercise at a moderate intensity (aerobic interval training). We will also include resistance training in each session. The supervised in-hospital exercise training sessions will last <1 hour, exercise training intensities will be individually tailored to each CPET. Exercise training will involve repeated exercise bouts of 3 minutes at a moderate exercise intensity (80%AT) followed by 2 minutes of exercise at a high intensity (50%Δ) for a predetermined amount of time. The home-based training programme will involve stair climbing (where possible) and brisk walking to achieve heart rates commensurate with those achieved during the in-hospital exercise training sessions.

No Intervention: Negative Control

Patients in the control arm will not undergo an exercise training program.

No Intervention: Observational

Patients who do not enrol in RCT will be enrolled in the observational arm

Outcome Measures

Primary Outcome Measures

Number of participants completing exercise sessions as a function of the whole programme. [12 weeks]
Adherence to the exercise training program
Adverse events [12 weeks]
Common Terminology on Complications (CTC AE v4)

Secondary Outcome Measures

Fitness levels as measured by Cardiopulmonary exercise testing (CPET) [12 weeks]
Physical fitness - oxygen uptake at anaerobic threshold
Timed up and go test (TUG) [12 weeks]
Physical fitness
Grip strength [12 weeks]
Physical fitness
Montreal score - Prognostic survival score [12 weeks]
Non small cell lung cancer stage, CRP, albumin, lactic acid dehydrogenase (LDH) and absolute neutrophil count/lymphocyte count ratio (N/L).
Health related quality of life questionnaire [12 weeks]
FACT-L quality of life questionnaire
Health related quality of life questionnaire [12 weeks]
Dukes Activity Status Index
Health related quality of life questionnaire [12 weeks]
International Physical Activity Questionnaire (IPAQ)
Health related quality of life questionnaire [12 weeks]
Godin Leisure Time Questionnaire (GLTEQ).
Physical activity [12 weeks]
Patients will wear a Sensewear Pro3 activity monitor (armband) or similar e.g. AX3 3-Axis Logging Accelerometer (wristband) for 72 hours. Number of steps in a 72 hours period will be calculated
Survival [1 year]
Overall survival
Response to chemotherapy [12 weeks]
Cross sectional imaging will be performed within 12 days of the third cycle of chemotherapy, to assess response to treatment. Scans will be reported according to the Response Evaluation Criteria for Solid Tumours (RECIST Version 1 http://www.irrecist.com/recist/recist-in-practice/01.html).
Fitness levels as measured by Cardiopulmonary exercise testing (CPET) [12 weeks]
Physical fitness - oxygen uptake at peak exercise

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female patients, aged over 18 years old
Histologically or cytologically confirmed NSCLC (adenocarcinoma, squamous cell carcinoma, large cell carcinoma, undifferentiated carcinoma or other)
Stage IIIb/IV disease
Patients being treated with first line gemcitabine and platinum based chemotherapy (other equivalent regimens may be considered on discussion with Judith Cave)
Performance status 0-2 (PS 2 have to be deemed fit enough to complete all cycles of chemotherapy).

Exclusion Criteria:

Unable to consent
Under 18 years
Unable to perform CPET
Significant cardiac ischaemia of > 1.5mm symptomatic and > 2mm asymptomatic observed on the baseline ECG
Weight of >145kg (weight limit for cycle ergometer)
Any other contraindication to CPET based on ACCP/ATS Guidelines and summarised in the table below.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospitals Southampton NHS Foundation Trust	Southampton		United Kingdom	SO16 6YD

Sponsors and Collaborators

University Hospital Southampton NHS Foundation Trust
Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust

Investigators

Principal Investigator: Sandy Jack, PhD, University Hospitals Southampton NHS Foundation Trust

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University Hospital Southampton NHS Foundation Trust

ClinicalTrials.gov Identifier:

NCT03334071

Other Study ID Numbers:

RHM CAN 0960
13/YH/0354

First Posted:

Nov 7, 2017

Last Update Posted:

Jul 8, 2019

Last Verified:

Jul 1, 2019

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Study Results

No Results Posted as of Jul 8, 2019