Condition category
Cancer
Date applied
04/12/2014
Date assigned
16/12/2014
Last edited
05/04/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Public

Primary contact

Mrs Judith Dixon-Hughes

ORCID ID

http://orcid.org/0000-0002-5596-4400

Contact details

CRUK CTU Glasgow
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom
0141 301 7540
judith.dixon@glasgow.ac.uk

Additional identifiers

EudraCT number

2013-003047-29

ClinicalTrials.gov number

Protocol/serial number

BALLAD 2013

Study information

Scientific title

A trial to evaluate the potential benefit of adjuvant chemotherapy for small bowel adenocarcinoma

Acronym

BALLAD

Study hypothesis

Adjuvant fluoropyrimidine chemotherapy results in an improved outcome (DFS and OS) over observation alone after potentially curative surgery for stage I, II and III SBA2. Adjuvant fluoropyrimidine and oxaliplatin chemotherapy results in an improved outcome (DFS and OS) over fluropyrimidine alone after potentially curative surgery for stage I, II and III small bowel adenocarcinoma.

Ethics approval

West of Scotland Research Ethics Service 1, 05/03/2015, ref: 15/WS/0011

Study design

Open-label randomised controlled multi-centre global trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

Small bowel adenocarcinoma

Intervention

Group 1: Patients will be randomised between observation and chemotherapy. Those patients who draw the chemotherapy arm and who have consented to this can go on to be randomised into the group 2 question. This is to be encouraged as it will add significant value and improve efficiency of the trial.
Group 2: Patients will be randomised to receive therapy with a fluoropyrimidine regimen or combination therapy of fluoropyrimidine plus oxaliplatin. Investigators must specify the fluoropyrimidine regimen at the time of randomisation for each individual patient. Any accepted institutional standard IV 5-FU/Folinic Acid regimen or oral capecitabine regimen may be used. The combination regimen is specified as oxaliplatin delivered as part of a standard institutional fluoropyrimidine combination regimen. Treatment will continue for up to 24 weeks

Intervention type

Drug

Phase

Phase III

Drug names

1. Capecitabine
2. 5-FU
3. Oxaliplatin

Primary outcome measures

Disease free survival is the primary end point for the trial. This is defined at time from randomisation to the first occurrence of the following events:
1. Disease relapse (confirmed by imaging)
2. Incidence of a new primary (confirmed by imaging and histology/cytology)
3. Death from any cause
Patients who experience none of these events are censored at the last date known to be alive.

Secondary outcome measures

1. Overall survival: The patient’s survival status is determined at each follow-up visit. After the mandated clinic visits survival status data will come from responsible cancer centres, cancer registries and national databases and include long-term passive follow-up data such as that collected through collaboration with the National Cancer Intelligence Network in the U.K.
2. Toxicity of chemotherapy: Toxicity will be assessed using CTCAE version 4.0. Only toxicities that are at least grade 2 will be recorded on the CRF
3. Quality of life: This is assessed using the EORTC QLQ-C30, EORTC QLQ-CR29 v2.1 and EQ-5D scales
Health Economics: Assess the cost-effectiveness of 24 weeks adjuvant chemotherapy in comparison to observation alone; and assess the cost-effectiveness of 24 weeks adjuvant 5FU/Capecitabine monotherapy compared to 5FU/Capecitabine plus Oxaliplatin. Outcomes will be reported as incremental cost per DFS and incremental cost per QALY. 4. Establishment of a central tissue bank for patients with SBA

Overall trial start date

01/03/2015

Overall trial end date

30/08/2022

Reason abandoned

Eligibility

Participant inclusion criteria

1. R0 resected stage I, II or III SBA
2. No evidence of residual or metastatic disease at laparotomy or on CT/MRI imaging of chest, abdomen and pelvis
3. Patients must be registered and randomised within 12 weeks of surgery and commence chemotherapy within 14 weeks of surgery
4. ECOG Performance Status of 0 or 1
5. Absolute neutrophil account ≥ 1.5 x109/l
6. Platelet count ≥ 100 x 109/l
7. Haemoglobin ≥90 g/l (previous transfusion is allowed)
8. AST and ALT ≤ 2.5 x upper limit of normal (ULN). (At least one of ALT or AST MUST be performed)
9. Creatinine clearance > 50 ml/min (calculated by Cockcroft Gault or Wright equation) or measured by EDTA
10. Serum bilirubin ≤ 1.5 x ULN
11. Signed and dated informed consent indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrolment
12. Age ≥ 16 years
13. Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests and other trial procedures

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

880

Participant exclusion criteria

1. Non-adenocarcinoma histology of small bowel tumour which includes but is not confined to lymphoma, GIST, carcinoid or other neuroendocrine tumour, squamous carcinoma, melanoma or sarcoma
2. Previous neo-adjuvant chemo(radio)therapy for SBA
3. Clinically significant cardiovascular disease (i.e. active or < 12 months since cerebrovascular accident, myocardial infarction, unstable angina, New York Heart Association [NYHA] grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, uncontrolled hypertension)
4. Pregnancy/lactation or of child bearing potential and not using medically approved contraception. (Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential)
5. Previous malignancy other than adequately treated in situ carcinoma of the uterine cervix or basal or squamous cell carcinoma of the skin, unless there has been a disease free interval of at least 3 years and treatment was with curative intent
6. Known or suspected dihydropyrimidine dehydrogenase (DPD) deficiency
7. Known untreated coeliac disease (may be enrolled if diet controlled), untreated chronic inflammatory bowel disease or other cause of malabsorption or intestinal obstruction
8. Grade ≥ 2 peripheral neuropathy
9. Administration of any investigational drug within 28 days or 5 half-lives, whichever is longer, prior to receiving the first dose of trial treatment
10. Previous hypersensitivity to platinum salts

Recruitment start date

01/03/2015

Recruitment end date

01/03/2020

Locations

Countries of recruitment

France, Japan, United Kingdom

Trial participating centre

Beatson West of Scotland Cancer Centre
-
United Kingdom

Sponsor information

Organisation

Greater Glasgow and Clyde Healthboard and University of Glasgow

Sponsor details

Research and Development Management Office
NHS Greater Glasgow and Clyde
Western Infirmary
38 Church Street
Glasgow
G11 6NT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Not defined

Funder name

Cancer Research UK

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

The study has been accepted for a trials in progress abstract for this years ASCO. Publication of study results in a peer reviewed journal is planned.

Intention to publish date

30/06/2023

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

05/04/2016: Publication and dissemination plan added. 30/03/2016: Ethics approval information added.