Nintedanib for Unicentric Castleman disease|Hyaline-vascular unicentric Castleman disease

Inclusion criteria

• {"criterion_text":"- Age equal to or greater than18 years\n- Written informed consent\n- Biopsy-proven diagnosis of hyaline-vascular Unicentric Castleman disease\n- Unresectable or partially resectable UCD lesion or surgery refusal\n- Available oral route\n- Affiliated to National French social security system (registered or being a beneficiary of such a scheme)"}

Exclusion criteria

• {"criterion_text":"- Synchronous Follicular Dendritic Cell sarcoma\n- 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\n- Major injuries in the 10 days prior to start of the study / Recent surgery with wound healing in progress (<14 days)\n- 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).\n- Contraindication to the experimental drug or auxiliary drugs listed in section 7.3\n- Enrolment in another interventional study(ongoing at the time of inclusion)\n- Known hypersensitivity to nintedanib, soy or peanut\n- 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)\n- Inability to obtain informed consent\n- Patients under guardianship or curatorship and protected adults\n- Liver transaminases (AST and/or ALT) >5N\n- End-stage liver disease (Child B or C cirrhosis)\n- End-stage renal failure (CrCl<30 mL/min)\n- Severe hemorrhagic or thromboembolic events in the past 6 months"}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Decrease >30% from baseline in Total Lesion Glycolysis (TLG) measured by 18F‑FDG PET/CT performed at Month 3 (M3) and Month 6 (M6)."}

Secondary endpoints

• {"endpoint_text":"- Number of adverse events (AEs), number of serious AEs, nindetanib discontinuation up to Month 9 (M9)","definition_or_measurement_approach":"Count and classification of adverse events and serious adverse events; nintedanib discontinuation tracked up to Month 9 (M9)."}
• {"endpoint_text":"- Variation from baseline in size, SUV and TLG percentage of the lesion at M3 and M6","definition_or_measurement_approach":"Change from baseline in lesion size, standardized uptake value (SUV) and Total Lesion Glycolysis (TLG) measured at Month 3 and Month 6 by imaging (PET/CT)."}
• {"endpoint_text":"- Change in the status of non-resectability of the UCD lesion at M6","definition_or_measurement_approach":"Assessment of resectability status at Month 6 compared with baseline (categorical change in resectability)."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"PNP assessed with Pemphigus Disease Area Index at M1, M3, M6, M9; bronchiolitis obliterans assessed by change from baseline in % predicted FEV1, FVC, TLC and DLCO at M3, M6, M9; serum autoantibody titers measured for listed antibodies."}
• {"endpoint_text":"- Occurrence of paraneoplastic pemphigus and/or myasthenia gravis during follow-up, up to M9","definition_or_measurement_approach":"Recording of new diagnoses/events of paraneoplastic pemphigus and/or myasthenia gravis during follow-up through Month 9."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"PDGFRB mutation status assessed by NGS; correlation analyses vs changes in lesion size, SUV and TLG at M3 and M6."}
• {"endpoint_text":"- Nintedanib residual plasma concentration at M1, M3, M6","definition_or_measurement_approach":"Measurement of plasma concentration of nintedanib at Month 1, Month 3 and Month 6; used to evaluate residual levels and correlation with response."}

France

Earliest CTIS Part Ii Submission Date

25-06-2024

Latest Decision Or Authorization Date

05-02-2025

Processing Time Days

225

Number Of Sites

6

Number Of Participants

13

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France