Nintedanib Treatment in Unicentric Castleman Disease

NCT06643091 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: APHP230820
• Study Type: interventional
• Target: 13
• Locations: 0 countries
• Sites: N/A

Brief Summary

Unicentric Castleman Disease (UCD) is a rare non-malignant localised disease involving one or more lymph nodes, associating germinal centre atrophy, mantle zone thickening and intense vascular proliferation penetrating the germinal centres. Patients usually seek medical attention because of a localised, sometimes compressive, lymph node or the development of life-threatening autoimmune complications (paraneoplastic pemphigus or PNP or myasthenia gravis or MG). The best treatment option is complete surgical excision, but it has been recently demonstrated that up to half of the patients cannot undergo surgery. In these patients, an efficient medical approach needs be defined, as no current medical treatment has demonstrated to lower morbidity and mortality. The cause of UCD is currently unknown and current data favour a scenario of stromal impairment leading to the loss of lymph node architecture rather than one of a primary hematopoietic disease. UCD lesions are often associated with synchronous follicular dendritic cell (FDC) proliferation and can sometimes evolve towards a true FDC sarcoma (FDCS), indicating a possible role for FDC, a germinal centre stromal cell component, in UCD pathogenesis. A recurrent somatic activating mutation in PDGFRB (p.N666S) has been recently described in the CD45 negative (non-hematopoietic) compartment of up to 17% UCD specimens. Moreover, activation of the VEGFR pathway is thought to play a role in the development of the disease, especially in the increased vascularity characteristic of the UCD lesion. Nintedanib is a commercially available tyrosine-kinase inhibitor targeting PDGF, VEGF and FGF receptors. The drug has obtained European Market Authorization in 2015 for the treatment of Non-Small Cell Lung Cancer and Idiopathic Pulmonary Fibrosis with a satisfactory safety profile. The hypothesis is that nintedanib could benefit patients with unresectable or partially resectable UCD.

Conditions

Castleman Disease

Keywords

Castleman disease

Outcome Measures

Primary Outcomes (1)

• Best response

  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

  Up to 6 months

Secondary Outcomes (40)

• Number of adverse events

  Up to 9 months

• Number of serious adverse events

  Up to 9 months

• Nindetanib discontinuation

  Up to 9 months

• Size of the lesion

  At 3 months

• Ssize of the lesion

  At 6 months

Study Arms (1)

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

EXPERIMENTAL

Drug: Nintedanib

Interventions

Nintedanib DRUG

Nintedanib150 mg twice a day for 6 months Or Nintedanib 100mg twice a day in case of dose adjustment Oral route (during meals)

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ (equal to or greater than) 18 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)
• Women of childbearing potential should be advised and agree to avoid becoming pregnant while receiving treatment and to use highly effective contraceptive methods at initiation of, during and at least 3 months after the last dose of treatment; pregnancy testing must be conducted prior to treatment and during treatment as appropriate; breast-feeding should be discontinued during treatment
• In male patients, with WOCBP partner(s), willingness to use adequate contraceptive measures to prevent his partner from becoming pregnant during the study, prior to administration of the first dose of study treatment until 3 months after the last dose of study treatment

You may not qualify if:

• Synchronous Follicular Dendritic Cell sarcoma
• Known hypersensitivity to nintedanib, soy or peanut or to any of the excipients of the experimental drug, or known hypersensitivity to the auxiliary drugs listed or to any of their excipients.
• Inability to obtain informed consent
• Patients under legal protection
• Liver transaminases (AST and/or ALT) \>3N
• 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
• Uncontrolled systemic illness such as chronic heart failure, unstable angina, hypertension; history of myocardial infarction or stroke or aneurysm
• Major injuries in the 10 days prior to start of the study, or Recent surgery with inadequate wound healing, or Abdominal surgery in the past 4 weeks.
• Severe pulmonary hypertension
• Bleeding risk, any of the following:
• Known genetic predisposition to bleeding.
• Patients who require

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Castleman Disease

Interventions

nintedanib

Condition Hierarchy (Ancestors)

Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

David Boutboul, MD

CONTACT

+33142499140; david.boutboul@aphp.fr

Jérôme Lambert, MD PhD

CONTACT

+33142499742; jerome.lambert@u-paris.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter open label and single-arm phase II trial

Study Record Dates

• First Submitted: September 13, 2024
• First Posted: October 15, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: October 15, 2024

Record last verified: 2024-09