NUCastle - Nintedanib treatment in Unicentric Castleman disease

Phase 2

Not yet recruiting

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

• Registration Number: 2023-510253-42-00
• Lead Sponsor: Assistance Publique Hopitaux De Paris

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-07-08
• Last Update Posted: 2025-02-05

Recruitment & Eligibility

• Status: Authorised, recruitment pending
• Sex: Not specified
• Target Recruitment: 13

Inclusion Criteria

Age equal to or greater than18 years

Written informed consent

Biopsy-proven diagnosis of hyaline-vascular Unicentric Castleman disease

Unresectable or partially resectable UCD lesion or surgery refusal

Available oral route

Affiliated to National French social security system (registered or being a beneficiary of such a scheme)

Exclusion Criteria

Synchronous Follicular Dendritic Cell sarcoma

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

Major injuries in the 10 days prior to start of the study / Recent surgery with wound healing in progress (<14 days)

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).

Contraindication to the experimental drug or auxiliary drugs listed in section 7.3

Enrolment in another interventional study(ongoing at the time of inclusion)

Known hypersensitivity to nintedanib, soy or peanut

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)

Inability to obtain informed consent

Patients under guardianship or curatorship and protected adults

Liver transaminases (AST and/or ALT) >5N

End-stage liver disease (Child B or C cirrhosis)

End-stage renal failure (CrCl<30 mL/min)

Severe hemorrhagic or thromboembolic events in the past 6 months

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
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		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 Outcome Measures

Name	Time	Method
Number of adverse events (AEs), number of serious AEs, nindetanib discontinuation up to Month 9 (M9)		Number of adverse events (AEs), number of serious AEs, nindetanib discontinuation up to Month 9 (M9)
Variation from baseline in size, SUV and TLG percentage of the lesion at M3 and M6		Variation from baseline in size, SUV and TLG percentage of the lesion at M3 and M6
Change in the status of non-resectability of the UCD lesion at M6		Change in the status of non-resectability of the UCD lesion at M6
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)		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)
Occurrence of paraneoplastic pemphigus and/or myasthenia gravis during follow-up, up to M9		Occurrence of paraneoplastic pemphigus and/or myasthenia gravis during follow-up, up to M9
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)		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)
Nintedanib residual plasma concentration at M1, M3, M6		Nintedanib residual plasma concentration at M1, M3, M6

Trial Locations

Locations (5)

Assistance Publique Hopitaux De Paris; 🇫🇷 Paris, France

Centre Hospitalier Universitaire De Dijon; 🇫🇷 Dijon, France

Centre Hospitalier Universitaire De Bordeaux; 🇫🇷 Pessac, France

Centre Hospitalier Regional De Marseille; 🇫🇷 Marseille, France

Centre Hospitalier Universitaire De Lille; 🇫🇷 Lille, France

Assistance Publique Hopitaux De Paris

🇫🇷Paris, France

David Boutboul

Site contact

0663214866

david.boutboul@aphp.fr

Bertrand DUNOGUE

Site contact

0158411436

bertrand.dunogue@aphp.fr