NUCastle - Nintedanib treatment in Unicentric Castleman disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

28 Jan 2026 → ongoing

Decision date (initial)

2024-07-08

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

DGOS

External identifiers

EU CT number

2023-510253-42-00

ClinicalTrials.gov

NCT06643091

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Evaluate the efficacy of nintedanib in decreasing Total Lesion Glycolysis (TLG) of the UCD lesion over a 6-month treatment.

Secondary objectives 6

1. Evaluation of the safety profile of nintedanib
2. Evaluation of size and metabolism of the UCD lesion under treatment
3. Evaluation of the resectability of the lesion after a 6-month nintedanib treatment
4. Evaluation of the evolution and occurrence of autoimmune-related complications under treatment
5. Evaluation of the mutational status of PDGFRB of the lesion (NGS technology, laboratoire dePharmacogénomique des tumeurs, Pr S. Mourah, Dr F. Jouenne)
6. Evaluation of nintedanib residual plasma concentration and correlation with response to treatment

Conditions and MedDRA coding

Adult patients aged 18 and over with unicentric hyalino-vascular Castleman's disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age equal to or greater than18 years
2. Written informed consent
3. Biopsy-proven diagnosis of hyaline-vascular Unicentric Castleman disease
4. Unresectable or partially resectable UCD lesion or surgery refusal
5. Available oral route
6. Affiliated to National French social security system (registered or being a beneficiary of such a scheme)

Exclusion criteria 14

1. Synchronous Follicular Dendritic Cell sarcoma
2. Known hypersensitivity to nintedanib, soy or peanut
3. For women of childbearing age: positive serum or urine pregnancy test at inclusion and during the study period, up to 3 months after the last dose (plasmatic at inclusion)
4. Inability to obtain informed consent
5. Patients under guardianship or curatorship and protected adults
6. Liver transaminases (AST and/or ALT) >5N
7. End-stage liver disease (Child B or C cirrhosis)
8. End-stage renal failure (CrCl<30 mL/min)
9. Severe hemorrhagic or thromboembolic events in the past 6 months
10. Uncontrolled systemic illness such as, chronic heart failure, unstable angina, hypertension, history or myocardial infarction in the 12 months prior to the start of the treatment
11. Major injuries in the 10 days prior to start of the study / Recent surgery with wound healing in progress (<14 days)
12. Bleeding risk, any of the following : a. Known genetic predisposition to bleeding. b. Patients who require 1. Fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin) 2. High dose antiplatelet therapy corresponding to a combination of two anti-platelet aggregation treatment (aspirin + an Inhibitor of P2Y12 receptor).
13. Contraindication to the experimental drug or auxiliary drugs listed in section 7.3
14. Enrolment in another interventional study(ongoing at the time of inclusion)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Best response over 6 months defined as >30% decrease from baseline in Total Lesion Glycolysis (TLG) measured by 18F FDG PET/CT performed at M3 and M6

Secondary endpoints 7

1. Number of adverse events (AEs), number of serious AEs, nindetanib discontinuation up to Month 9 (M9)
2. Variation from baseline in size, SUV and TLG percentage of the lesion at M3 and M6
3. Change in the status of non-resectability of the UCD lesion at M6
4. Evolution of autoimmune-related complications: *Paraneoplastic pemphigus/Bronchiolitis Obliterans: Improvement/Worsening/ Stable disease based on: - pemphigus disease area index (for PNP) at M1, M3, M6 and M9 - bronchiolitis obliterans: change from baseline of the percent of predicted forced expiratory volume in 1 second (FEV1), in forced vital capacity, total lung capacity and DLCO at M3, M6 and M9 - serum antibody titers (anti desmoglein 1/3,anti desmoplakin,anti envoplakin, anti periplakin)
5. Occurrence of paraneoplastic pemphigus and/or myasthenia gravis during follow-up, up to M9
6. Evaluation of the mutational status of PDGFRB of the lesion (NGS technology) and correlation with treatment response (variation in size, SUV, TLG at M3 and M6)
7. Nintedanib residual plasma concentration at M1, M3, M6

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

1 Avenue Claude Vellefaux

City

Paris

Postcode

75010

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Investigateur coordinateur

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Investigateur coordinateur

Locations

1 EU/EEA country · 6 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

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