ARDVARC- Advancing Rare Disorders: Vascular mAlformations Research Network with CaNVAS: Pilot Core

Children'S Hosp Of Philadelphia, Philadelphia PA

Investigators

Abstract

ARDVARC Pilot/Feasibility Governance Core: Project Summary Rapid exploration of the molecular alterations underpinning of complex vascular malformations (cVM) has identified potential therapeutic targets for these patients. However, the current portfolio of genotype-driven clinical trials harnessing these advancements has lagged behind scientific discovery and remains extremely limited. Furthermore, there is unclear prioritization of treatment modalities, therapeutic agents, quantitative imaging methods, and response criteria. In particular, PIK3CA-related overgrowth spectrum (PROS) with VMs, complex lymphatic anomalies (CLA), and extra-cranial arteriovenous malformations (eAVM) remain specific diseases with significant unmet needs. The overall aim of this Rare Disease Clinical Research Consortium (RDCRC), ARDVARC, is to construct an interdisciplinary research team (patient advocacy groups, clinical, translational, basic, and health services scientists) with the RDCRN to enhance clinical trial readiness for patients with cVM. This Pilot/Feasibility Governance Core will serve two essential functions to advance clinical research and clinical trial readiness for cVM. First, this core will establish a standard blueprint for evaluation and prioritization of novel Treatments and Assessments that focus on cVM. Second, this core will provide pilot funding to support and encourage preclinical, clinical, and logistical studies that address limitations or roadblocks preventing the clinical implementation of novel Treatments and Assessments. With the separate Steering and Grants Committees we will develop processes for each of these functions that are rigorous, transparent, and fair with evaluation of the efficiency and efficacy of these functions for continual process improvement. The ARDVARC mission will be further supported by incorporating clinical trial-embedded correlative studies, prioritizing access to precious biologic patient samples with annotated clinical correlates, providing access/exposure to RDCRC/RDCRN and advocacy group resources, integrating junior investigators into Core activities, and fostering collaboration both within the RDCRC and beyond. Our team has rich expertise in vascular malformations, clinical and translational research, and team management uniquely suiting them to lead this Pilot/Feasibility Core. Together the Pilot/Feasibility Core aims will not only accelerate research in rare cVM but also unify efforts to advance treatments and assessment methods for the unmet needs of this severely impacted rare disease population.