Clinical Research Directory

International PPB/DICER1 Registry

PPB has strong genetic implications, with a unique set of conditions in an individual or their family, occurring mostly in childhood and adolescence. The International PPB/DICER1 Registry first reported DICER1 germline loss-of-function variations in individuals with PPB and their family members. Conditions associated with DICER1 include Sertoli-Leydig cell tumor (SLCT), gynandroblastoma, ovarian sarcoma, peritoneal PPB, lung cysts, renal cysts, cystic nephroma (CN), anaplastic sarcoma of the kidney (ASK), Wilms tumor, primary DICER1-associated central nervous system (CNS) sarcoma, pineoblastoma, pituitary blastoma, multinodular goiter, thyroid carcinoma, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma (CBME), juvenile hamartomatous intestinal polyps, embryonal rhabdomyosarcoma (ERMS) and undifferentiated sarcoma. DICER1 variations may also be associated with macrocephaly and overgrowth syndrome. The International PPB/DICER1 Registry estimates that 30-50 cases of Type I and Ir PPB and 40-60 cases of Types II and III PPB are diagnosed annually worldwide. In 2009, the International Pleuropulmonary Blastoma Registry began a prospective study to collect treatment data on individuals for whom therapy decisions were made by their treating institution.

Sequential CD146 and GPC3 CAR-T Cell Therapy in Advanced Ovarian Cancer

This is a multicenter, open-label Phase 1/2 clinical trial evaluating the safety and preliminary efficacy of sequentially administered CD146-targeted and GPC3-targeted CAR-T cell therapy in patients with advanced relapsed or refractory ovarian cancer. Eligible patients will undergo lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by an infusion of autologous CD146-directed CAR-T cells (Arm A) and a subsequent infusion of autologous GPC3-directed CAR-T cells (Arm B). The Phase 1 portion will assess safety, tolerability, and dose-limiting toxicities (DLTs) to determine a recommended Phase 2 dose, while the Phase 2 portion will evaluate efficacy endpoints including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Patients will be followed for up to 36 months after CAR-T infusion to monitor long-term outcomes and adverse events.