Plain English Summary
Trial website
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 measure
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 (if study stopped)
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
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
Basic results (scientific)
Publication list