Exercise Intervention During Chemotherapy in Advanced Lung Cancer Patients

NCT ID: NCT03334071

Last Updated: 2019-07-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-04-04

Study Completion Date

2019-12-30

Brief Summary

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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.

2\) 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.

5\) To assess the feasibility of the translation of in-hospital exercise training to home-based training during chemotherapy.

6\) 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).

Detailed Description

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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.

Conditions

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Non Small Cell Lung Cancer Non Small Cell Lung Cancer Stage IIIB Non Small Cell Lung Cancer Metastatic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Exercise intervention
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Investigators Outcome Assessors
Cardiopulmonary exercise testing assessor, outcome/toxicity assessor

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Exercise

Intervention Type BEHAVIORAL

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.

Negative Control

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Observational

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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.

Intervention Type BEHAVIORAL

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust

OTHER_GOV

Sponsor Role collaborator

University Hospital Southampton NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sandy Jack, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospitals Southampton NHS Foundation Trust

Locations

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University Hospitals Southampton NHS Foundation Trust

Southampton, , United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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13/YH/0354

Identifier Type: OTHER

Identifier Source: secondary_id

RHM CAN 0960

Identifier Type: -

Identifier Source: org_study_id

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