BALLAD – PRODIGE 33

A TRIAL TO EVALUATE THE POTENTIAL BENEFIT OF ADJUVANT CHEMOTHERAPY FOR SMALL BOWEL ADENOCARCINOMA

Trial Status In preparation
Phase Phase III
Type of cancer Small Bowel Adenocarcinoma (SBA)
Study design

An open-label, randomised, controlled, multi-centre, trial with disease free survival as the primary end point. The study is carried out as a worldwide collaboration, in which Belgium is taking part.

Objectives
  1. Assessment of the efficacy of observation versus 24 weeks of adjuvant post-
    operative chemotherapy in resected stage I-III small bowel adenocarcinoma (SBA).
  2. Assessment of the efficacy of 24 weeks of adjuvant post-operative fluoropyrimidine
    ‘monotherapy’ regimen versus fluoropyrimidine plus Oxaliplatin combination
    chemotherapy regimen in resected stage I-III small bowel adenocarcinoma (SBA).
Inclusion Main 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.
Exclusion Main 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
  11. Patients with clinically significant, active infections, or any other serious medical condition in which chemotherapy is contraindicated will be excluded
  12. 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
  13. 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.
Treatment schedule

Group 1 patients, where there is uncertain value of adjuvant chemotherapy, will be
randomised to observation versus chemotherapy. The chemotherapy will be 24 weeks
fluoropyrimidine with or without Oxaliplatin or these patients can be randomised to
receive Oxaliplatin or not as per Group 2 patients below. The choice of chemotherapy
must be specified prior to randomisation.
Group 2 patients, where there is certain value of adjuvant chemotherapy, will be
randomised to receive 24 weeks fluoropyrimidine chemotherapy either with or without
Oxaliplatin. The choice of fluoropyrimidine must be specified prior to randomisation.

Study Period

Recruitment Start Date (FPI): 2018
Recruitment Finish Date (LPI): 2023
Follow-up Period End Date (LPO): 2031
End of trial is defined by the last patient last visit

Study Coordinators

Prof. Marc Peeters, Universitair Ziekenhuis Antwerpen

Participating Groups

FFCD

Participating centres

UZ Antwerpen
AZ Delta Roeselare
AZ Sint-Lucas Gent
AZ Sint-Maarten Mechelen
AZ Turnhout
CHC St-Joseph Liège
ULB Erasme Bruxelles
Cliniques Universitaires Saint Luc Bruxelles

Protocol summary https://clinicaltrials.gov/ct2/show/NCT02502370?term=BALLAD&cond=Adenocarcinoma&rank=1
NCT number NCT02502370
EudraCT 2015-000729- 5
Interest to participate clinicaltrials@bgdo.org
More info clinicaltrials@bgdo.org