Clinical trial NCT03334071: Exercise Intervention During Chemotherapy in Advanced Lung Cancer Patients
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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Non Small Cell Lung Cancer
Non Small Cell Lung Cancer Stage IIIB
Non Small Cell Lung Cancer Metastatic
Lead sponsor: University Hospital Southampton NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust
First posted: 2017-11-07
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Exercise intervention
Primary purpose: TREATMENT

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.

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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants completing exercise sessions as a function of the whole programme.
timeFrame: 12 weeks
measure: Adverse events
timeFrame: 12 weeks
Secondary outcomes:
measure: Fitness levels as measured by Cardiopulmonary exercise testing (CPET)
timeFrame: 12 weeks
measure: Timed up and go test (TUG)
timeFrame: 12 weeks
measure: Grip strength
timeFrame: 12 weeks
measure: Montreal score - Prognostic survival score
timeFrame: 12 weeks
measure: Health related quality of life questionnaire
timeFrame: 12 weeks
measure: Health related quality of life questionnaire
timeFrame: 12 weeks
measure: Health related quality of life questionnaire
timeFrame: 12 weeks
measure: Health related quality of life questionnaire
timeFrame: 12 weeks
measure: Physical activity
timeFrame: 12 weeks
measure: Survival
timeFrame: 1 year
measure: Response to chemotherapy
timeFrame: 12 weeks
measure: Fitness levels as measured by Cardiopulmonary exercise testing (CPET)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Southampton
country: United Kingdom
facility: University Hospitals Southampton NHS Foundation Trust
Study officials:
affiliation: University Hospitals Southampton NHS Foundation Trust
name: Sandy Jack, PhD
role: PRINCIPAL_INVESTIGATOR
References: