PRODIGE 33 - BALLAD - Phase III study to evaluate the benefit of adjuvant chemotherapy in small bowel adenocarcinoma.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Dijon

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Oct 2024 → ongoing

Decision date (initial)

2024-10-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

PHRC

External identifiers

EU CT number

2024-515299-11-00

EudraCT number

2015-000729-35

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

- To evaluate the efficacy of 12 cycles (or 8 cycles if capecitabine) of adjuvant chemotherapy versus observation alone after resection of stage I-III small bowel adenocarcinoma (SBI).
- To evaluate the efficacy of 12 cycles (or 8 cycles if capecitabine) of adjuvant treatment with 5-FU or capecitabine monotherapy versus 5-FU or capecitabine plus oxaliplatin after resection of stage I-III small bowel adenocarcinoma (SBA).

Secondary objectives 6

1. Overall survival
2. Chemotherapy toxicity (NCI-CTC version 4.0)
3. Cost-effectiveness of therapeutic alternatives
4. Quality of life
5. Biological collection for patients with this rare cancer
6. Medico-economic study

Conditions and MedDRA coding

SMALL BOWEL ADENOCARCINOMA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. R0 resected stage I, II, III small bowel adenocarcinoma (SBA)
2. No residual or metastatic disease visible on CT/MRI TAP
3. Patient to be registered and randomised within 12 weeks of surgery, and able to start chemotherapy within 14 weeks of surgery
4. ECOG ≤ 1
5. Age ≥ 18 years
6. Biological tests: neutrophils ≥ 2000/mm3; platelets ≥ 100000/mm3; haemoglobin ≥ 9 g/dL (prior transfusion possible) and bilirubin ≤ 1.5 x ULN.
7. ASAT et ALAT ≤ 2,5 x LSN
8. Creatinine clearance > 50 mL/min (calculated using the Cockcroft Gault formula)
9. Women of childbearing potential (post-menopausal women must have been amenorrhoeic for at least 12 months to be considered not of childbearing potential) must use contraception during treatment and for at least 4 months after stopping treatment; for male patients, contraception must be used during treatment and for at least 6 months after stopping treatment.
10. Dated and signed informed consent prior to inclusion

Exclusion criteria 14

1. Small bowel tumour with non-adenocarcinoma histology, including but not limited to lymphoma, GIST, carcinoid or other neuroendocrine tumours, squamous cell carcinoma, melanoma and sarcoma.
2. Neoadjuvant chemo(radio)therapy for SBA
3. Clinically significant cardiovascular disease: active or < 12 months since stroke, myocardial infarction, unstable angina, congestive heart failure NYHA grade II or higher, severe cardiac arrhythmia requiring treatment, or uncontrolled hypertension.
4. History of cancer, except treated carcinoma in situ of the uterine cervix or basal or squamous cell carcinoma of the skin, unless treated with curative intent and considered cured for at least 3 years.
5. Partial or complete dihydropyrimidine dehydrogenase (DPD) deficiency, defined by uracilemia ≥ 16ng/ml
6. Known untreated celiac disease (inclusion possible if controlled by diet), untreated chronic inflammatory bowel disease, or other causes of malabsorption or intestinal obstruction.
7. Peripheral neuropathy grade ≥ 2
8. Pregnant and breast-feeding women
9. Administration of any other investigational drug within 28 days prior to the first cycle of study treatment
10. Known hypersensitivity to platinum salts
11. Patients with an active, clinically significant infection or any other serious medical condition for which chemotherapy is contraindicated
12. Patients with untreated vitamin B12 deficiency should not receive chemotherapy containing folinic acid. However, this patient may be eligible for capecitabine-based chemotherapy.
13. Patients with clinically significant neurosensorial hearing impairment should not receive oxaliplatin. However, this patient may be randomised in group 1 to either observation alone or fluoropyrimidine monotherapy.
14. Inability to comply with scheduled visits, therapeutic regimens, biological examinations and any other study procedures.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease-free survival (DFS) is the primary endpoint of the study. It is defined as the time from randomisation to the first occurrence of the following events: - Recurrence of disease (confirmed by imaging) - Development of a new primary tumour (confirmed by imaging and histology/cytology) - Death Patients who do not present any of these events will be censored at the date of last news.

Secondary endpoints 4

1. Overall survival: the survival status of patients will be determined at each follow-up visit.
2. Chemotherapy toxicity: toxicity will be assessed using the CTCAE version 4.0 classification. Only toxicities of at least grade 2 will be recorded in the CRF.
3. Quality of life: this will be assessed using the EORTC QLQ-C30, EORTC QLQ-CR29 and EQ-5D questionnaires.
4. Health economics: to assess the cost-effectiveness of 24 weeks of adjuvant chemotherapy compared with observation alone, and of 24 weeks of adjuvant 5-FU/capecitabine monotherapy compared with 5-FU/capecitabine plus oxaliplatin. The results will be reported in terms of incremental cost per DFS and incremental cost per QALY.

Investigational products

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

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Dijon

Sponsor organisation

Centre Hospitalier Universitaire De Dijon

Address

1 Boulevard Jeanne D Arc, Bp 77908 Bp 77908

City

Dijon

Postcode

21000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Dijon

Contact name

Thomas APARICIO

Public contact point

Organisation

Centre Hospitalier Universitaire De Dijon

Contact name

Thomas APARICIO

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 14 files

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

Application history

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