BALLAD Belgium - A trial to evaluate the potential benefit of adjuvant chemotherapy for small bowel adenocarcinoma. The Belgian component of the Global Ballad pooled data analysis.

2024-518349-85-01 Protocol Ballad Belgium Therapeutic confirmatory (Phase III) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 8 sites · Protocol Ballad Belgium

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Authorised, recruitment pending
Participants planned 30
Countries 1
Sites 8

small bowel adenocarcinoma

Assessment of the efficacy of observation versus 24 weeks of adjuvant post-operative chemotherapy in resected stage I-IV small bowel adenocarcinoma (SBA). Assessment of the efficacy of 24 weeks of adjuvant post-operative fluoropyrimidine ‘monotherapy’ regimen versus fluoropyrimidine plus Oxaliplatin combination chemoth…

Key facts

Sponsor
Groupe Belge D'Oncologie Digestive
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Neoplasms [C04]
Decision date (initial)
2024-11-20
Transition trial
Yes
Low-intervention
No
Rare-disease indication
Yes
Vulnerable population
No
Funding sources
Kom op tegen Kanker-VZW

External identifiers

EU CT number
2024-518349-85-01
EudraCT number
2018-002831-65
ClinicalTrials.gov
NCT04257461

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Assessment of the efficacy of observation versus 24 weeks of adjuvant post-operative chemotherapy in resected stage I-IV small bowel adenocarcinoma (SBA).
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-IV small bowel adenocarcinoma (SBA).

Secondary objectives 2

  1. Assess the toxicity of chemotherapy
  2. Establish a central tissue bank for patients with this rare cancer

Conditions and MedDRA coding

small bowel adenocarcinoma

Regulatory references

Plan to share IPD
Yes
IPD plan description
After analysis of the data, the results including methodological logistical aspects may be published as approved by the GLOBAL BALLAD TSC during digestive oncology congresses and in medical journals.
EU CT numberTitleSponsor
2024-518349-85-00 BALLAD Belgium - A trial to evaluate the potential benefit of adjuvant chemotherapy for small bowel adenocarcinoma. The Belgian component of the Global Ballad pooled data analysis. Groupe Belge D'Oncologie Digestive
2015-000729-35 BALLAD - A TRIAL TO EVALUATE THE POTENTIAL BENEFIT OF ADJUVANT CHEMOTHERAPY FOR SMALL BOWEL ADENOCARCINOMA , PRODIGE 33 - FFCD 1405 - BALLAD ÉTUDE DE PHASE III VISANT À ÉVALUER LE BÉNÉFICE D'UNE CHIMIOTHÉRAPIE ADJUVANTE DANS L'ADÉNOCARCINOME DE L'INTESTIN GRÊLE
2013-003047-29 BALLAD. A trial to evaluate the potential benefit of adjuvant chemotherapy for small bowel adenocarcinoma., BALLAD- undersøgelse af adjuverende kemoterapi efter operation for adenocarcinom i tolvfingetarmen eller tyndtarmen. , BALLAD- undersøgelse af adjuverende kemoterapi efter operation for adenocarcinom i tolvfingetarmen eller tyndtarmen.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

  1. R0 resected stage I, II, III or IV SBA
  2. No evidence of residual or metastatic disease at laparotomy and 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 x10^9/l
  6. Platelet count ≥ 100 x 10^9/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 ≥ 18 years
  13. Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests and other trial procedures.

Exclusion criteria 15

  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 treatment consisted of resection alone or with a single installation of intravesical 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 with very low potential for recurrence can be discussed with the CI 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Disease free survival (defined as time from randomisation to recurrence, development of new primary or death from any cause).

Secondary endpoints 3

  1. Overall survival
  2. toxicity
  3. clinico-pathological, epidemiological and molecular profiling of SBA.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 11

Fluorouracil Accord Healthcare 50 mg/ml, solution pour injection ou perfusion

PRD415445 · Product

Active substance
Fluorouracil
Substance synonyms
5-FLOUROURACIL, 5-FLUORO-1H-PYRIMIDINE-2,4-DIONE, 5-FLUOROURACIL, 5-FU
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENIOUS INFUSION
Max daily dose
2800 mg/m2 milligram(s)/sq. meter
Max total dose
33600 mg/m2 milligram(s)/sq. meter
Max treatment duration
24 Week(s)
Authorisation status
Authorised
ATC code
L01BC02 — FLUOROURACIL
Marketing authorisation
BE415712
MA holder
ACCORD HEALTHCARE B.V.
MA country
Belgium
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Fluorouracil Accord Healthcare 50 mg/ml, solution pour injection ou perfusion

PRD415448 · Product

Active substance
Fluorouracil
Substance synonyms
5-FLOUROURACIL, 5-FLUORO-1H-PYRIMIDINE-2,4-DIONE, 5-FLUOROURACIL, 5-FU
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS INFUSION
Max daily dose
2800 mg/m2 milligram(s)/sq. meter
Max total dose
33600 mg/m2 milligram(s)/sq. meter
Max treatment duration
24 Week(s)
Authorisation status
Authorised
ATC code
L01BC02 — FLUOROURACIL
Marketing authorisation
BE345597
MA holder
ACCORD HEALTHCARE B.V.
MA country
Belgium
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Fluorouracil Accord Healthcare 50 mg/ml, solution pour injection ou perfusion

PRD415446 · Product

Active substance
Fluorouracil
Substance synonyms
5-FLOUROURACIL, 5-FLUORO-1H-PYRIMIDINE-2,4-DIONE, 5-FLUOROURACIL, 5-FU
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS INFUSION
Max daily dose
2800 mg/m2 milligram(s)/sq. meter
Max total dose
33600 mg/m2 milligram(s)/sq. meter
Max treatment duration
24 Week(s)
Authorisation status
Authorised
ATC code
L01BC02 — FLUOROURACIL
Marketing authorisation
BE345606
MA holder
ACCORD HEALTHCARE B.V.
MA country
Belgium
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Fluorouracil Accord Healthcare 50 mg/ml, solution pour injection ou perfusion

PRD415447 · Product

Active substance
Fluorouracil
Substance synonyms
5-FLOUROURACIL, 5-FLUORO-1H-PYRIMIDINE-2,4-DIONE, 5-FLUOROURACIL, 5-FU
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENIOUS INFUSION
Max daily dose
2800 mg/m2 milligram(s)/sq. meter
Max total dose
33600 mg/m2 milligram(s)/square meter
Max treatment duration
24 Week(s)
Authorisation status
Authorised
ATC code
L01BC02 — FLUOROURACIL
Marketing authorisation
BE345624
MA holder
ACCORD HEALTHCARE B.V.
MA country
Belgium
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Fluorouracil Accord Healthcare 50 mg/ml oplossing voor injectie of infusie

PRD415449 · Product

Active substance
Fluorouracil
Substance synonyms
5-FLOUROURACIL, 5-FLUORO-1H-PYRIMIDINE-2,4-DIONE, 5-FLUOROURACIL, 5-FU
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
2800 mg/m2 milligram(s)/sq. meter
Max total dose
33600 mg/m2 milligram(s)/sq. meter
Max treatment duration
24 Week(s)
Authorisation status
Authorised
ATC code
L01BC02 — FLUOROURACIL
Marketing authorisation
BE345615
MA holder
ACCORD HEALTHCARE B.V.
MA country
Belgium
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Xeloda 500 mg film-coated tablets

PRD9863934 · Product

Active substance
Capecitabine
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
2500 mg/m2 milligram(s)/sq. meter
Max total dose
280000 mg/m2 milligram(s)/sq. meter
Max treatment duration
24 Week(s)
Authorisation status
Authorised
ATC code
L01BC06 — CAPECITABINE
Marketing authorisation
EU/1/00/163/002
MA holder
CHEPLAPHARM ARZNEIMITTEL GMBH
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Xeloda 150 mg film-coated tablets

PRD9863933 · Product

Active substance
Capecitabine
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
2500 mg/m2 milligram(s)/sq. meter
Max total dose
280000 mg/m2 milligram(s)/sq. meter
Max treatment duration
24 Week(s)
Authorisation status
Authorised
ATC code
L01BC06 — CAPECITABINE
Marketing authorisation
EU/1/00/163/001
MA holder
CHEPLAPHARM ARZNEIMITTEL GMBH
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

ELVORINE 25 mg/2,5 mL, solution injectable

PRD422923 · Product

Active substance
Levoleucovorin
Substance synonyms
Levofolinic acid, L-Folinic acid
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENIOUS INFUSION
Max daily dose
400 mg/m2 milligram(s)/sq. meter
Max total dose
4800 mg/m2 milligram(s)/sq. meter
Max treatment duration
24 Week(s)
Authorisation status
Authorised
ATC code
V03AF04 — CALCIUM LEVOFOLINATE
Marketing authorisation
34009 348 988 1 5
MA holder
PFIZER HOLDING FRANCE
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

ELVORINE 50 mg/5 mL, solution injectable

PRD495689 · Product

Active substance
Levoleucovorin
Substance synonyms
Levofolinic acid, L-Folinic acid
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENIOUS INFUSION
Max daily dose
400 mg/m2 milligram(s)/sq. meter
Max total dose
4800 mg/m2 milligram(s)/sq. meter
Max treatment duration
24 Week(s)
Authorisation status
Authorised
ATC code
V03AF04 — CALCIUM LEVOFOLINATE
Marketing authorisation
34009 348 989 8 3
MA holder
PFIZER HOLDING FRANCE
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

ELOXATIN 5 mg/ml concentraat voor oplossing voor infusie

PRD482016 · Product

Active substance
Oxaliplatin
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS INFUSION
Max daily dose
130 mg/m2 milligram(s)/sq. meter
Max total dose
1040 mg/m2 milligram(s)/sq. meter
Max treatment duration
24 Week(s)
Authorisation status
Authorised
ATC code
L01XA03 — OXALIPLATIN
Marketing authorisation
BE281601
MA holder
SANOFI BELGIUM
MA country
Belgium
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

ELOXATIN 5 mg/ml concentraat voor oplossing voor infusie

PRD482023 · Product

Active substance
Oxaliplatin
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENIOUS INFUSION
Max daily dose
130 mg/m2 milligram(s)/sq. meter
Max total dose
1040 mg/m2 milligram(s)/sq. meter
Max treatment duration
24 Week(s)
Authorisation status
Authorised
ATC code
L01XA03 — OXALIPLATIN
Marketing authorisation
BE281592
MA holder
SANOFI BELGIUM
MA country
Belgium
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Groupe Belge D'Oncologie Digestive

2 Total trials 1 Recruiting
Academic / Non-commercial
Sponsor organisation
Groupe Belge D'Oncologie Digestive
Address
Leuvensesteenweg 643
City
Zaventem
Postcode
1930
Country
Belgium

Scientific contact point

Organisation
Groupe Belge D'Oncologie Digestive
Contact name
Timon Vandamme

Public contact point

Organisation
Groupe Belge D'Oncologie Digestive
Contact name
Ine De Bruyne

Locations

1 EU/EEA country · 8 investigational sites

By country

CountryMS statusPlanned subjectsSites
Belgium Authorised, recruitment pending 30 8
Rest of world — 0 —

Investigational sites

Belgium

8 sites · Authorised, recruitment pending
CHC MontLegia
Gastro-enterology and hemato-oncology, Boulev. De Patience Et Beajonc 2, 4000, Liege
Cliniques Universitaires Saint-Luc
Digestive oncology, Hippokrateslaan 10, Batiment 54, Sint-Lambrechts-Woluwe
Az Sint-Lucas
Gastro-enterology, Sint-Lucaslaan 29, 8310, Brugge
Centre Hospitalier Universitaire De Liege
Gastro-enterology and digestive oncology, Avenue De L'hopital 1, 4000, Liege
AZ Turnhout
Gastro-enterology and digestive oncology, Steenweg Op Merksplas 44, 2300, Turnhout
Antwerp University Hospital
Oncology, Drie Eikenstraat 655, 2650, Edegem
Algemeen Ziekenhuis Delta
Maag-, Darm- en leverziekten, Deltalaan 1, 8800, Roeselare
Hopital Erasme
Gastro-enterology and digestive oncology, Lennikse Baan 808, 1070, Anderlecht

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 31 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D BALLAD protocol 1
Recruitment arrangements (for publication) K informedconsent_patientrecruitmentprocedure_en 1
Subject information and informed consent form (for publication) L Eng_ ICF PIS bio only 1
Subject information and informed consent form (for publication) L Eng_ ICF PIS Group1 1
Subject information and informed consent form (for publication) L Eng_ ICF PIS Group2 1
Subject information and informed consent form (for publication) L Eng_ ICF-PIS assoc bio study 1
Subject information and informed consent form (for publication) L FR_ ICF-PIS assoc bio study 1
Subject information and informed consent form (for publication) L FR_ ICF-PIS bio only 1
Subject information and informed consent form (for publication) L FR_ ICF-PIS Group 1 1
Subject information and informed consent form (for publication) L FR_ ICF-PIS Group 2 1
Subject information and informed consent form (for publication) L ICF-procedure 1.1
Subject information and informed consent form (for publication) L NL_ ICF-PIS assoc bio 1
Subject information and informed consent form (for publication) L NL_ ICF-PIS bio only 1
Subject information and informed consent form (for publication) L NL_ ICF-PIS Group 1 1
Subject information and informed consent form (for publication) L NL_ ICF-PIS Group 2 1
Subject information and informed consent form (for publication) L Patient Diary-FR 1
Subject information and informed consent form (for publication) L Patient Diary-NL 1
Subject information and informed consent form (for publication) L questionnaire_CR29-DU 1
Subject information and informed consent form (for publication) L questionnaire_CR29-FR 1
Subject information and informed consent form (for publication) L questionnaire_EQ5D3L-DU 1
Subject information and informed consent form (for publication) L questionnaire_EQ5D3L-FR 1
Subject information and informed consent form (for publication) L questionnaire_QLQC30-DU 1
Subject information and informed consent form (for publication) L questionnaire_QLQC30-FR 1
Summary of Product Characteristics (SmPC) (for publication) G Smcp_ELOXATIN_Dutch 1
Summary of Product Characteristics (SmPC) (for publication) G Smcp_ELOXATIN_French 1
Summary of Product Characteristics (SmPC) (for publication) G Smcp_ELVORINE_Dutch 1
Summary of Product Characteristics (SmPC) (for publication) G Smcp_ELVORINE_French 1
Summary of Product Characteristics (SmPC) (for publication) G Smcp_FLUOROURACIL_Dutch 1
Summary of Product Characteristics (SmPC) (for publication) G Smcp_FLUOROURACIL_French 1
Summary of Product Characteristics (SmPC) (for publication) G Smcp_XELODA_Dutch 1
Summary of Product Characteristics (SmPC) (for publication) G Smcp_XELODA_French 1

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-11-08 Belgium Acceptable
2024-11-19
 2024-11-20

Related clinical trials