Condition category
Cancer
Date applied
08/01/2015
Date assigned
12/01/2015
Last edited
16/06/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Many breast cancer patients are above an ideal weight, with high body fat and low muscle stores. Many patients gain fat and lose muscle during chemotherapy, and too much fat and low muscle stores can make chemotherapy less effective and increase its side effects. The aim of this study is to test the potential beneficial effects of a calorie-restricted diet and resistance exercise on breast cancer patients scheduled to receive chemotherapy. Resistance exercise is also known as strength training, and is performed to increase muscle and bone strength.

Who can participate?
Patients aged over 18 with breast cancer who are scheduled to receive chemotherapy

What does the study involve?
Participants are randomly allocated to one of two groups. One group follows a diet and exercise programme which includes a calorie-restricted diet and resistance training 3 times per week. The other group do resistance (strength) training 3 times per week. Both groups are asked to follow these programmes during their current course of chemotherapy, and are phoned by the study researchers every 3 weeks during the study to check their progress and provide further advice and support. Research nurses in the treatment centre review patients at each chemotherapy treatment and assess weight and any side effects of the chemotherapy. The following outcomes are assessed: time to disease progression, chemotherapy toxicity, quality of life, fatigue, change in weight, waist circumference, fat and muscle mass.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
University Hospital of South Manchester (UK)

When is the study starting and how long is it expected to run for?
February 2015 to April 2018

Who is funding the study?
Anticancer Fund (UK)

Who is the main contact?
Mary Pegington

Trial website

Contact information

Type

Scientific

Primary contact

Mrs Mary Pegington

ORCID ID

Contact details

University Hospital of south Manchester
Genesis Prevention Centre
Wythenshawe Hospital
Southmoor Road
Manchester
M23 9LT
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

18070

Study information

Scientific title

A randomised phase II trial of intermittent energy restriction and resistance exercise in women receiving chemotherapy for advanced breast cancer

Acronym

B-AHEAD3

Study hypothesis

This randomised trial will test the potential beneficial effects of a calorie restricted diet and resistance exercise compared to a resistance exercise programme on disease progression amongst 134 metastatic breast cancer patients scheduled to receive paclitaxel or capecitabine chemotherapy.

This is a randomised phase II screening trial. If the results from this diet and exercise weight loss intervention are positive we will look to perform a national phase III study.

Ethics approval

14/NW/1396

Study design

Randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Topic: Cancer; Subtopic: Breast Cancer; Disease: Breast

Intervention

Group 1: Diet and exercise. This group have an individual session with the trial dietitian and are asked to follow our 5:2 calorie restricted diet tailored to their needs and preferences. This group will also have an individual session with the trial physiotherapist or exercise specialist to teach them the resistance exercise which they will be asked to do three times a week. Resistance exercise is also known as strength training, and it is performed to increase the strength and mass of muscles, bone strength.

Group 2: Exercise. This group will also have an individual session with the trial physiotherapist or exercise specialist to teach them the resistance exercises which they will be asked to do three times a week. They will be given general written dietary advice on healthy eating, coping with the side effects of chemotherapy and food hygiene.

Both groups will be phoned by BAHEAD by 3 researchers every 3 weeks during the study to check their progress and provide further advice and support. Research nurses in the treatment centre will review patients at each chemotherapy treatment and assess weight and any side effects of the chemotherapy.

We will examine the difference between the two groups on:
Time to disease progression, chemotherapy toxicity, quality of life, fatigue, change in weight, waist circumference, fat and muscle mass which we can assess from their routine treatment CT scan.

Intervention type

Mixed

Phase

Drug names

Primary outcome measures

Progression-free survival (PFS)

Secondary outcome measures

Time to Treatment Failure (TTF) i.e. the time from randomisation to disease progression, death

Overall trial start date

01/02/2015

Overall trial end date

01/04/2018

Reason abandoned

Eligibility

Participant inclusion criteria

As of 17/05/2016:
1.Women with histologically confirmed breast cancer
2. Patients with ABC, i.e. locally advanced disease that is not amenable to curative surgical resection or with metastatic disease
3. HER2 positive or negative
4. ER and/or PR positive or negative
5. If ER positive there is no restriction on the number of lines of previous endocrine therapy for ABC
6. Performance status 0 or 1
7. Predicted life expectancy ≥ 3 months
8. BMI ≥24 kg/m2
9. Expressing a wish to lose weight
10. Not already entered or planned to enter a trial of an investigational medicinal product (IMP) for this line of therapy
11. Age >18 (can be pre or post menopausal)
12. Measurable or non-measurable disease by RECIST v1.1
13. Patients with brain or leptomeningeal metastases are eligible as long as all sites have been treated with radiotherapy (+/- surgery) with evidence of disease control at least 8 weeks after the last dose
14. Women in whom further endocrine therapy is planned after chemotherapy are eligible. The treating clinician must state what endocrine therapy is planned before chemotherapy is initiated
15. Women with thyroid dysfunction are eligible provided they are euthyroid and on a stable dose of thyroxine for the last 6 months

Previous:
1. Women with histologically confirmed breast cancer
2. Patients with advanced breast cancer (ABC) i.e. locally advanced disease that is not amenable to curative surgical resection or with metastatic disease
3. Her2 negative by IHC defined as 0/1+ or 2+ with FISH/DDISH/CISH ratio <2.0
4. ER and or PR positive or negative
5 If ER positive there is no restriction on the number of lines of previous endocrine therapy for ABC
6. No more than one line of chemotherapy for locally advanced or metastatic breast cancer. A line of chemotherapy is defined as a treatment given with palliative intent and of at least 4 weeks duration. If chemotherapy was given for less than 4 weeks and stopped due to excess toxicity, with NO evidence of progression either clinically, biochemically or radiologically, then this will not be counted as a line of therapy. If an attempt to downstage a locally advanced tumour with chemotherapy was made in the absence of metastatic breast cancer (MBC), and the tumour operated upon, then this does not count as a line of therapy for ABC. In contrast, if the tumour remained inoperable then this treatment should be included as a line of therapy for ABC.
7. In the opinion of the treating clinician suitable for treatment with ‘full dose’ weekly paclitaxel (8090mg/m2 weekly with no rest weeks) or capecitabine 10001250mg/m2 twice daily for 14 days followed by a rest week.
8. Performance status 0 or 1
9. BMI>25 kg / m 2 and body fat >30% (determined from impedence/ or CT scan) or waist circumference > 80cm
10. Expressing a wish to lose weight
11. Not already entered or planned to enter a trial of an investigational medicinal product (IMP) for this line of therapy
12. Age >18 (can be pre or post menopausal)
13. Measurable or nonmeasurable disease by RECIST v1.1
14. Patients with brain or leptomeningeal metastases are eligible as long as all sites have been treated with radiotherapy (+/surgery) with evidence of disease control at least 8 weeks after the last dose
15. Women in whom further endocrine therapy is planned after chemotherapy are eligible. The treating clinician must state what endocrine therapy is planned before chemotherapy is initiated.
16. Women with thyroid dysfunction are eligible provided they are euthyroid and on a stable dose of thyroxine for the last 6 months

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 134; UK Sample Size: 134

Participant exclusion criteria

As of 17/05/2016:
1. Physical or psychiatric conditions which may reduce compliance to and the safety of diet or resistance exercise, e.g.
1.1. Serious digestive and/or absorptive problems, including active inflammatory bowel disease.
1.2. Psychiatric disorders or conditions, e.g. history of eating disorders, untreated major depression, psychosis, substance abuse, severe personality disorder.
1.3. Bone metastases at risk of pathological fracture or that would limit resistance exercise through pain in all three areas of the body that are covered by the resistance exercises (upper limbs, trunk and lower limbs). Metastases may be ok if other areas of the body can safely be exercised.
2. Medications affecting adiposity or muscle mass and function and energy intake e.g. continuous daily steroids for longer than 4 weeks (short term steroids with chemotherapy are acceptable)
3. Diabetics on insulin or sulphonylureas (glibenclamide, gliclazide, glimepiride, glipizide, tolbutamide) as they could experience hypoglycaemia on restricted days of the intermittent diet (diabetics treated with diet alone or with any other medication including metformin are eligible)
4. Greater than Day 15 of this course of chemotherapy.
5. Visceral metastases that, in the opinion of the treating clinician, would result in death within 3 months if no response was achieved with this line of chemotherapy
6. Symptomatic or uncontrolled brain or leptomeningeal metastases

Previous:
1. Physical or psychiatric conditions which may reduce compliance to and the safety of diet or resistance exercise eg. serious digestive and/or absorptive problems, including active inflammatory bowel disease.
2. Psychiatric disorders or conditions, e.g. history of eating disorders, untreated major depression, psychosis, substance abuse, severe personality disorder.
3. Bone metastases at risk of pathological fracture or that would limit resistance exercise through pain.
4. Medications affecting adiposity or muscle mass and function and energy intake e.g. continuous daily steroids for longer than 4 weeks (short term steroids with chemotherapy are acceptable)
5. Diabetics on insulin or sulphonylureas (glibenclamide, gliclazide, glimepiride, glipizide, tolbutamide) as they could experience hypoglycaemia on restricted days of the intermittent diet (diabetics treated with diet alone or with any other medication including metformin are eligible)
6. Already commenced this course of first or second line chemotherapy
7. Visceral metastases that, in the opinion of the treating clinician, would result in death within 3 months if no response were achieved with this line of chemotherapy
8. Patients relapsing within 12 months of adjuvant/neoadjuvant chemotherapy
9. Symptomatic or uncontrolled brain or Leptomeningeal metastases

Recruitment start date

01/02/2015

Recruitment end date

01/04/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University Hospital of South Manchester
Genesis Prevention Centre Wythenshawe Hospital Southmoor Road
Manchester
M23 9LT
United Kingdom

Sponsor information

Organisation

University Hospital of South Manchester NHS Foundation Trust (UK)

Sponsor details

Southmoor Road
Wythenshawe
Manchester
M23 9LT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Anticancer Fund (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

16/06/2016: Plain English summary added. 08/06/2016: the following changes were made to the trial record: 1. The recruitment end date was changed from 01/04/2016 to 01/04/2017. 2. The overall trial end date was changed from 01/04/2017 to 01/04/2018. 17/05/2016: the overall trial end date was changed from 01/04/2016 to 01/04/2017.