Recurrent Langerhans Cell Histiocytosis Clinical Trial
Official title:
Phase 2 Study of DAY101 in Relapsed and Refractory Langerhans Cell Histiocytosis
This phase II trial tests the safety, side effects and best dose of DAY101 in treating patients with Langerhans cell histiocytosis that are growing, spreading, or getting worse (progressive), has come back (relapsed), or does respond to treatment (refractory). DAY101 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and blocks over-active growth pathways in cancer cells. Giving DAY101 may cause the tumor to stop growing or to shrink for a period of time.
PRIMARY OBJECTIVE: I. To determine overall response rate (ORR) for children and young adults with relapsed or refractory Langerhans cell histiocytosis (LCH) treated with tovorafenib (DAY101) after 2 cycles. SECONDARY OBJECTIVES: I. To determine nature and severity of adverse events in patients treated with DAY101 for relapsed or refractory LCH. II. To determine event-free survival (EFS) at 1 year (after 12 cycles at end of therapy) in children and young adults with relapsed and refractory LCH treated with DAY 101. III. To determine durability of response in children and young adults with relapsed or refractory LCH treated with DAY101 following cessation of therapy in patients with complete response (CR) at 1 year. IV. To determine progression-free (and relapse-free) survival (PFS) and overall survival (OS) in children and young adults with relapsed or refractory LCH treated with DAY101 for up to 1 year. EXPLORATORY OBJECTIVES: I. To determine potential role of pathogenic tumor mutation in response to DAY101, and to evaluate changes in bone marrow and peripheral blood cell populations carrying pathogenic mutations in response to DAY101 therapy. Ia. Define somatic mutations in LCH lesion biopsies. Ib. Determine impact of DAY101 on bone marrow and blood BRAFV600E+ mononuclear cells. Ic. Determine impact of DAY101 on cerebral spinal fluid and disease response. Id. To determine the performance of standardized immunohistochemical analysis of LCH lesion biopsies. OUTLINE: This is a dose escalation study of tovorafenib. Patients receive tovorafenib orally (PO) once weekly on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy and fludeoxyglucose F-18 (FDG)-positron emission tomography (PET). After completion of study treatment, patients are followed up at 28 days and then every 3, 6, 9, and 12 months. ;
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