PRODIGE 76-IMMUNOBILADJ: Capecitabine plus durvalumab or capecitabine alone as adjuvant therapy in patients with resected biliary tract carcinoma. A non-comparative randomized phase II study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondation Franc.Cancerologie Digestive

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12], Diseases [C] - Digestive System Diseases [C06]

Trial duration

completed 29 Aug 2023

Decision date (initial)

2023-07-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Fédération Francophone de Cancérologie Digestive

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To assess the disease-free survival rate at 18 months of durvalumab plus capecitabine in patients with resected Biliary Tract Carcinoma (The disease relapse will be defined by the appearance of local/ distant recurrence or 2nd primary biliary tract cancer by investigator’s evaluation).

Secondary objectives 5

1. To assess the safety profile in the two arms
2. To assess the DFS in the two arms (investigator’s evaluation)
3. To assess overall survival (OS) in the two arms
4. To assess health-related Quality of life (HRQoL) in the two arms
5. To assess prognostic and predictive biomarkers in terms of survival (blood, tumour, and imaging)

Conditions and MedDRA coding

Biliary tract carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
2. Willing and able to comply with the protocol for the duration of the study including undergoing treatment (able to take medicinal products by mouth) and scheduled visits and examinations including follow up and for biological study.
3. BTC (perihilar CCA, distal CCA, intrahepatic CCA, or gallbladder carcinoma) with complete macroscopic resection (R0/R1)
4. No evidence of metastatic or recurrent disease on post-operative CT-scan (< 4 weeks before randomization)
5. Surgery for primary tumour > 4 weeks and < 12 weeks prior to the first dose of investigational product
6. Absence of dihydropyrimidine dehydrogenase (DPD) deficiency (defined by uracilemia < 16 ng/mL)
7. Age ≥ 18 years
8. Eastern Cooperative Oncology Group – Performance Status (ECOG – PS) 0-1
9. Have archival tissue sample that has been identified and confirmed as available for study
10. Adequate organs functions
11. Body weight > 30 kg
12. Life expectancy ≥ 3 months
13. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female of childbearing potential and pre-menopausal patients.
14. Patient affiliated to a social security scheme

Exclusion criteria 23

1. Previous neoadjuvant systemic chemotherapy or intra-arterial therapy (TACE, TAE, SIRT…) before surgery.
2. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) or supportive care clinical study or during the follow-up period of an interventional study
3. Mixed histology (hepatocholangiocarcinoma)
4. Ampullary carcinoma
5. History of allogenic organ transplantation
6. Unresolved post-operative complications that may be at risk for adjuvant therapy
7. Any systemic steroid therapy (> 10 mg daily dose of prednisone or equivalent) whatever the duration of this corticotherapy
8. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), and Hepatitis B Virus (HBV)-Hepatitis C Virus (HCV) co-infection or HBV-HepD co-infection , or human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies)
9. Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri
10. Prior treatment with capecitabine or any immune ICI, including durvalumab or any other anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody
11. Uncontrolled massive pleural effusion or massive ascites
12. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Immune hyperthyroitidis disease, rheumatoid arthritis, hypophysitis, uveitis, etc]), that has required systemic treatment (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
13. History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT-scan
14. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
15. Live vaccine administration within 30 days prior to the first dose of study treatment
16. Known or suspected allergy or hypersensitivity to any of the study drugs or any of the study drug excipients (capecitabine or durvalumab)
17. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 ms
18. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the participant, in the opinion of the treating investigator
19. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational product
20. Pregnancy/lactation
21. Tutelage or guardianship
22. Participation in another clinical study with an investigational product during the last 4 weeks
23. Child B or C cirrhosis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease-Free Survival rate at 18 months

Secondary endpoints 5

1. Safety profile in two arms
2. DFS in two arms
3. overall survival in two arms
4. health-related Quality of life in the two arms
5. Prognostic and predictive biomarkers in terms of survival

Investigational products

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

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondation Franc.Cancerologie Digestive

Sponsor organisation

Fondation Franc.Cancerologie Digestive

Address

7 Boulevard Jeanne D Arc

City

Dijon Cedex

Postcode

21079

Country

France

Scientific contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

coordinator

Public contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

coordinator

Locations

1 EU/EEA country · 27 investigational sites

By country

Investigational sites

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 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