Evaluating the potential benefit of adjuvant chemotherapy for small bowel adenocarcinoma
| ISRCTN | ISRCTN15070952 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15070952 |
| EudraCT/CTIS number | 2013-003047-29 |
| ClinicalTrials.gov number | NCT04257461 |
| Secondary identifying numbers | BALLAD 2013 |
- Submission date
- 04/12/2014
- Registration date
- 16/12/2014
- Last edited
- 11/04/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Contact information
Mrs Sarah Bradley
Public
Public
CRUK CTU Glasgow
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom
| Phone | 0141 301 7540 |
|---|---|
| sarah.bradley@glasgow.ac.uk |
Study information
| Study design | Open-label randomised controlled multi-centre global trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a participant information sheet |
| Scientific title | A trial to evaluate the potential benefit of adjuvant chemotherapy for small bowel adenocarcinoma |
| Study acronym | BALLAD |
| Study objectives | Current study hypothesis as of 12/07/2019: Adjuvant fluoropyrimidine chemotherapy results in an improved outcome (DFS and OS) over observation alone after potentially curative surgery for stage I, II, III and IV 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, III and IV small bowel adenocarcinoma Previous 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(s) | West of Scotland Research Ethics Service 1, 05/03/2015, ref: 15/WS/0011 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/03/2015 |
| Completion date | 28/02/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | The minimum sample size required will be 580 patients and maximum will be 880 patients |
| Total final enrolment | 69 |
| Key inclusion criteria | Current participant inclusion criteria as of 12/07/2019: 1. R0 resected stage I, II, III or IV 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 14 weeks of surgery and commence chemotherapy within 16 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 Previous 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 |
| Key exclusion criteria | Current participant exclusion criteria as of 12/07/2019: 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. Adenocarcinoma arising in the appendix or colorectum 3. Previous neo-adjuvant chemo(radio)therapy for SBA 4. 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) 5. 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) 6. Previous invasive or non-invasive malignancy except: (i) Ductal Carcinoma in Situ (DCIS) of the breast where treatment consisted of resection alone, (ii) cervical carcinoma in situ where treatment consisted of resection alone, (iii) basal cell or squamous cell carcinoma where treatment consisted of resection alone or radiotherapy, (iv) superficial bladder carcinoma where treatments consisted of resection alone or with a single installation of intracescical chemotherapy or with BCG treatment, (v) other cancers where the patient has been disease-free for at least 3 years and treatment was with curative intent and (vi) other cancers wih very low potential for recurrence can be discussed with the CI or his approved representative through the Glasgow CRUK Clinical Trials Unit where eligibility will be considered on an individual basis 7. Known or suspected dihydropyrimidine dehydrogenase (DPD) deficiency 8. Known untreated coeliac disease (may be enrolled if diet controlled), untreated chronic inflammatory bowel disease or other cause of malabsorption or intestinal obstruction 9. Grade ≥ 2 peripheral neuropathy 10. Administration of any investigational drug within 28 days or 5 half-lives, whichever is longer, prior to receiving the first dose of trial treatment. 11. Previous hypersensitivity to platinum salts 12. Patients with clinically significant, active infections, or any other serious medical condition in which chemotherapy is contraindicated will be excluded 13. 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 14. 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 15. Any patient receiving treatment with brivudine, sorivudine and analogues Previous 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 |
| Date of first enrolment | 25/08/2015 |
| Date of final enrolment | 31/08/2022 |
Locations
Countries of recruitment
- Belgium
- France
- Japan
- United Kingdom
Study participating centre
Beatson West of Scotland Cancer Centre
-
United Kingdom
United Kingdom
Sponsor information
Greater Glasgow and Clyde Healthboard and University of Glasgow
Hospital/treatment centre
Hospital/treatment centre
Research and Development Management Office
NHS Greater Glasgow and Clyde
Western Infirmary
38 Church Street
Glasgow
G11 6NT
Scotland
United Kingdom
"ROR" |
https://ror.org/05kdz4d87 |
|---|
Funders
Funder type
Not defined
Cancer Research UK
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/08/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| 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. |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 6 | 16/07/2021 | 26/11/2021 | No | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
Editorial Notes
11/04/2024: The ClinicalTrials.gov number was added.
13/09/2022: The following changes were made to the trial record:
1. Total final enrolment added.
2. The overall trial end date was changed from 31/08/2025 to 28/02/2025.
3. The intention to publish date was changed from 31/08/2026 to 31/08/2025.
26/11/2021: Recruitment to this study is no longer paused and the following changes have been made:
1. The recruitment end date has been changed from 01/07/2021 to 31/08/2022.
2. The overall trial end date has been changed from 30/08/2022 to 31/08/2025.
3. The intention to publish date has been changed from 30/06/2023 to 31/08/2026.
4. The protocol (not peer reviewed) has been uploaded as an additional file.
09/04/2020: Due to current public health guidance, recruitment for this study has been paused.
12/07/2019: The following changes were made to the trial record:
1. The study hypothesis was updated.
2. Belgium was added to the countries of recruitment.
3. The public contact was changed from "Judith Dixon-Hughes, Judith.dixon@glasgow.ac.uk" to "Sarah Bradley ssarah.bradley@glasgow.ac.uk"
4. The inclusion criteria were changed.
5. The exclusion criteria were changed.
6. The target number of participants was changed from 880 to The minimum sample size required will be 580 patients and maximum will be 880 patients.
7. The recruitment start date was changed from 01/03/2015 to 25/08/2015.
8. The recruitment end date was changed from 01/03/2020 to 01/07/2021.
05/04/2016: Publication and dissemination plan added.
30/03/2016: Ethics approval information added.
