Small Bowel AdenocarcinomaPhase 3BALLADNCT04257461
A Trial to Evaluate the Potential Benefit of Adjuvant Chemotherapy for Small Bowel Adenocarcinoma
A Phase 3 study testing Fluoropyrimidine and Oxaliplatin in people with Small Bowel Adenocarcinoma, run by Belgian Group of Digestive Oncology at 9 sites in Belgium.
Trial summary
An open-label, randomised, controlled, multi-centre, trial with disease free survival as the primary end point. The worldwide collaboration is referred to as GLOBAL BALLAD and consists of a number of individual parallel prospective studies addressing the same objectives with similar designs brought together under the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Bowel Adenocarcinoma
- What is being tested?
- Fluoropyrimidine and Oxaliplatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 9 sitesBelgium
- Study dates
- 20 Feb 2020to 31 Dec 2025
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- R0 resected stage I, II or III SBA
- No evidence of residual or metastatic disease at laparotomy and on CT/MRI imaging of chest, abdomen and pelvis.
- Patients must be registered and randomised within 12 weeks of surgery and commence chemotherapy within 14 weeks of surgery
- ECOG Performance Status of 0 or 1
- Absolute neutrophil account ≥ 1.5 x109/l
- Platelet count ≥ 100 x 109/l
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- Haemoglobin ≥90 g/l (previous transfusion is allowed)
- AST and ALT ≤ 2.5 x upper limit of normal (ULN). (At least one of ALT or AST MUST be performed)
- Creatinine clearance > 50 ml/min (calculated by Cockcroft Gault or Wright equation) or measured by EDTA
- Serum bilirubin ≤ 1.5 x ULN
- Signed and dated informed consent indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrolment.
- Age ≥ 18 years
- Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests and other trial procedures.
Who cannot join
- 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.
- Previous neo-adjuvant chemo(radio)therapy for SBA
- 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)
- 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)
- 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
- Known or suspected dihydropyrimidine dehydrogenase (DPD) deficiency
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- Known untreated coeliac disease (may be enrolled if diet controlled), untreated chronic inflammatory bowel disease or other cause of malabsorption or intestinal obstruction
- Grade ≥ 2 peripheral neuropathy
- Administration of any investigational drug within 28 days or 5 halflives, whichever is longer, prior to receiving the first dose of trial treatment.
- Previous hypersensitivity to platinum salts
- Patients with clinically significant, active infections, or any other serious medical condition in which chemotherapy is contraindicated will be excluded
- Patients with untreated vitamin B12 deficiency are excluded from receiving folinic acid as part of their chemotherapy regimen. However, these patients may be eligible for treatment with capecitabine fluoropyrimidine therapy, where no folinic acid is administered as part of the treatment regimen
- Patients with clinically significant sensorineural hearing impairment are excluded from receiving oxaliplatin but will be eligible for the fluoropyrimidine monotherapy provided as a clinician's choice for patients in group 1 randomised to either observation or chemotherapy
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Belgium9 sites
Onze-Lieve-Vrouw Ziekenhuis Aalst
Aalst, Oost-Vlaanderen, 9300
UZ Antwerpen
Antwerp, Antwerp, 2650
ULB Erasme
Brussels, Brussels Capital, 1070
Cliniques Universitaires Saint-Luc UCL
Brussels, Brussels Capital, 1200
AZ St-Lucas
Ghent, Oost-Vlaanderen, 9000
CHC MontLégia
Liège, Liège, 4000
CHU Liège
Liège, Liège, 4000
AZ Delta
Roeselare, West-Vlaanderen, 8800
AZ Turnhout
Turnhout, Antwerpen, 2300
About this study
Official title: BALLAD BELGIUM: A Trial to Evaluate the Potential Benefit of Adjuvant Chemotherapy for Small Bowel Adenocarcinoma
An open-label, randomised, controlled, multi-centre, trial with disease free survival as the primary end point. The worldwide collaboration is referred to as GLOBAL BALLAD and consists of a number of individual parallel prospective studies addressing the same objectives with similar designs brought together under the framework of the International Rare Cancer Initiative. This protocol is for BALLAD BELGIUM, which is the component of GLOBAL BALLAD.
Read the detailed description
The utility of adjuvant chemotherapy in the management of Small Bowel Adenocarcinoma (SBA) remains unproven and awaits the results of a large, global, prospective, phase III, randomised, controlled trial. Across the 830 million population of North America and Europe, there are approximately 3,000 patients with R0 resected and potentially cured SBA every year who would be potentially eligible for such an adjuvant chemotherapy trial.
Given the absence of good-quality and evidence-based data, it has been agreed that a trial considering adjuvant chemotherapy versus no chemotherapy was appropriate for patients with stage I-IV SBA in whom the oncologist and patient feel that the benefit of adjuvant chemotherapy is uncertain. For those patients with stage I-IV SBA who, with their oncologists, feel that the potential benefit of adjuvant chemotherapy is certain (and hence are not willing to accept randomisation to the 'no chemotherapy' arm), a randomisation between single agent fluoropyrimidine versus doublet fluoropyrimidine and oxaliplatin chemotherapy will be offered. Tumour stage will be used as a stratification factor. Those patients who do not consent to be randomised will be offered registration to allow collection of demographic, clinicopathological, epidemiological and survival data, thereby making optimal use of the rare patient population available. In addition, archival Formalin Fixed Paraffin Embedded (FFPE) tissue and contemporaneous venous blood samples will be collected from every registered patient to allow molecular profiling and future translational research. A questionnaire about underlying risk factors (e.g. Crohn's disease, coeliac disease, Lynch syndrome etc) will be completed along with the other collected data on all registered patients.
The trial hypotheses are that:
- Adjuvant chemotherapy results in an improved outcome (DFS and OS) over observation alone after potentially curative R0 surgery for stage I, II, III and IV SBA
- Adjuvant fluoropyrimidine and oxaliplatin chemotherapy results in an improved outcome (DFS and OS) over fluropyrimidine alone after potentially curative R0 surgery for stage I, II, III and IV SBA.
- Conditions
- Small Bowel Adenocarcinoma
- Being tested
- Fluoropyrimidine, Oxaliplatin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluoropyrimidineDrug
Also called Capecitabine, LV5FU2
Monotherapy: 12 cycles of 5FU or 8 cycles of Capecitabine. The choice of fluoropyrimidine must be specified prior to randomisation.
OxaliplatinDrug
Also called Xeloda
Bichemotherapy: Oxaliplatine combined with Fluoropyrimidine.
| Study group | Role | What they receive |
|---|---|---|
| Group1 Arm A | No intervention | Observation only |
| Group 1 Arm B | Other | Mono- or bichemotherapy: fluoropyrimidine with or without Oxaliplatin (choice by physician/patient or by randomisation) Receives: Drug: Fluoropyrimidine; Drug: Oxaliplatin |
| Group 2 Arm C | Other | Monochemotherapy: fluoropyrimidine Receives: Drug: Fluoropyrimidine |
| Group 2 ARM D | Other | Bichemotherapy: fluoropyrimidine with oxaliplatin Receives: Drug: Fluoropyrimidine; Drug: Oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
efficacy assessed by the 3-year Disease-free survival
This is defined as time from randomisation to the first occurrence of the following events:
- Disease relapse (confirmed by imaging)
- Incidence of a new primary (confirmed by imaging and histology/cytology)
- Death from any cause
Measured: 3 years from randomisation
Secondary outcomes (6)
efficacy assessed by the 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.
Measured: 5 years from randomisation
safety assessed by the 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
Measured: until 1 month after treatment
quality of life as assessed using the EORTC (European Organisation for Research and Treatment of Cancer) Quality of Life Questionnaire Core 30
This will be completed at 9, 12, 18 and 24 months post randomisation for all arms of the trial. Minimum and maximum values do not apply for this scale.
Measured: until end of study, up to 5 years from randomisation
quality of life as assessed using the EORTC (European Organisation for Research and Treatment of Cancer) Quality of Life Questionnaire Colo-Rectal module 29
This will be completed at 9, 12, 18 and 24 months post randomisation for all arms of the trial. Minimum and maximum values do not apply for this scale.
Measured: until end of study, up to 5 years from randomisation
quality of life as assessed using the EuroQol 5 dimension scale (EQ-5D)
This will be completed at 9, 12, 18, 24, 30, 36, 48, 60 72 and 84 months post randomisation for all arms of the trial. Minimum and maximum values do not apply for this scale.
Measured: until end of study, up to 5 years from randomisation
Exploratory: clinical applicability of the study results assessed by the translational research on blood and tissue
The aim is to establish a biobank of SBA tissue and blood with complete and comprehensive trial quality follow-up data which may act as the foundation for many future collaborative research projects and for combined projects with other funded tissue collections.
Measured: Will be collected at the end of study, up to 5 years from randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2020
- Study start20 Feb 2020
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Small Bowel AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Belgian Group of Digestive Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- Kom Op Tegen Kanker, Cancer Research UK
- Responsible party
- Sponsor
- Investigators
- Timon Vandamme, Prof, Principal investigator, Coordinating Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04257461
- Sponsor's protocol ID
- BALLAD BELGIUM
- Acronym
- BALLAD
- Status last verified
- Feb 2024
- First submitted
- 9 Jan 2020
- Last updated
- 6 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No