A Trial to Evaluate the Potential Benefit of Adjuvant Chemotherapy for Small Bowel Adenocarcinoma

NCT04257461 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: BALLAD BELGIUM
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 9

Brief 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 framework of the International Rare Cancer Initiative. This protocol is for BALLAD BELGIUM, which is the component of GLOBAL BALLAD.

Conditions

Small Bowel Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• 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

  3 years from randomisation

Secondary Outcomes (6)

• efficacy assessed by the overall survival

  5 years from randomisation

• safety assessed by the toxicity of chemotherapy

  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

  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

  until end of study, up to 5 years from randomisation

• quality of life as assessed using the EuroQol 5 dimension scale (EQ-5D)

  until end of study, up to 5 years from randomisation

Study Arms (4)

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)

Drug: Fluoropyrimidine; Drug: Oxaliplatin

Group 2 Arm C

OTHER

Monochemotherapy: fluoropyrimidine

Drug: Fluoropyrimidine

Group 2 ARM D

OTHER

Bichemotherapy: fluoropyrimidine with oxaliplatin

Drug: Fluoropyrimidine; Drug: Oxaliplatin

Interventions

Fluoropyrimidine DRUG

Monotherapy: 12 cycles of 5FU or 8 cycles of Capecitabine. The choice of fluoropyrimidine must be specified prior to randomisation.

Also known as: Capecitabine, LV5FU2

Group 1 Arm B; Group 2 ARM D; Group 2 Arm C

Oxaliplatin DRUG

Bichemotherapy: Oxaliplatine combined with Fluoropyrimidine.

Also known as: Xeloda

Group 1 Arm B; Group 2 ARM D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Belgian Group of Digestive Oncology: lead
• Kom Op Tegen Kanker: collaborator
• Cancer Research UK: collaborator

Study Sites (9)

AZ Turnhout

Turnhout, Antwerpen, 2300, Belgium

Location

UZ Antwerpen

Antwerp, Antwerp, 2650, Belgium

Location

ULB Erasme

Brussels, Brussels Capital, 1070, Belgium

Location

Cliniques Universitaires Saint-Luc UCL

Brussels, Brussels Capital, 1200, Belgium

Location

CHC MontLégia

Liège, Liège, 4000, Belgium

Location

CHU Liège

Liège, Liège, 4000, Belgium

Location

Onze-Lieve-Vrouw Ziekenhuis Aalst

Aalst, Oost-Vlaanderen, 9300, Belgium

Location

AZ St-Lucas

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

AZ Delta

Roeselare, West-Vlaanderen, 8800, Belgium

Location

MeSH Terms

Interventions

Capecitabine; Oxaliplatin

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Officials

• Timon Vandamme, Prof

  Coordinating Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2020
• First Posted: February 6, 2020
• Study Start: February 20, 2020
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: February 6, 2025

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (9)