Testing of Tazemetostat in Combination With Topotecan and Pembrolizumab in Patients With Recurrent Small Cell Lung Cancer : Phase I Dose Escalation and Expansion Study of Tazemetostat in Combination With Topotecan and Pembrolizumab in Recurrent Small Cell Lung Cancer

PRIMARY OBJECTIVES:I. To determine the maximum tolerated dose (MTD) of tazemetostat hydrobromide (tazemetostat) in combination with topotecan hydrochloride (topotecan) and pembrolizumab in patients with recurrent extensive stage-small cell lung cancer (ES-SCLC), by reviewing dose-limiting toxicities (DLTs) in cycle 1 (21 days). (Dose-Escalation Cohort) II. To select the recommended phase II dose (RP2D) for a combination of tazemetostat, topotecan and pembrolizumab, based on pharmacodynamic (PD) parameters as well as overall efficacy and tolerability. (Dose-Escalation Cohort) III. To evaluate safety and tolerability of tazemetostat in combination with topotecan and pembrolizumab. (Expansion Cohort)SECONDARY OBJECTIVES:I. To observe and record anti-tumor activity. II. To determine in a very preliminary fashion, the efficacy of a combination of tazemetostat, topotecan and pembrolizumab in recurrent ES-SCLC by assessing overall response rate (ORR), progression-free survival (PFS), duration of response (DOR) and overall survival (OS).EXPLORATORY OBJECTIVES:I. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to ribonucleic acid (RNA) sequencing (RNA-Seq).II. To assess modulation of EZH2 targets including SLFN11 and MHC among others. III. To identify potential predictive biomarkers of response. IV. To identify mechanisms of drug sensitivity and resistance using deoxyribonucleic acid (DNA)- and RNA-based assessment platforms.V. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome.VI. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the National Cancer Institute (NCI) Early-Phase and Experimental Clinical Trials Biospecimen Bank (EET Biobank) at Nationwide Children's Hospital.VII. Characterize circulating cell-free DNA (cfDNA).OUTLINE: This is a dose-escalation study of tazemetostat followed by a dose-expansion study.Patients receive tazemetostat orally (PO) twice daily (BID) on days 1-21, pembrolizumab intravenously (IV) over 30 minutes on day 1, and topotecan IV over 30 minutes on days 1-5. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan throughout the study and may also undergo biopsy and collection of blood on study.After completion of study treatment, patients are followed every 3 months after removal from study treatment until study closure or death, whichever occurs first..

Medienart:	Klinische Studie

Erscheinungsjahr:	2024
Erschienen:	2024

Enthalten in:	ClinicalTrials.gov - (2024) vom: 26. März Zur Gesamtaufnahme - year:2024

Sprache:	Englisch

Links:	Volltext [kostenfrei]

Themen:	610 Carcinoma Carcinoma, Small Cell Phase: Phase 1 Recruitment Status: Recruiting Recurrence Small Cell Lung Carcinoma Study Type: Interventional

Anmerkungen:	Source: Link to the current ClinicalTrials.gov record., First posted: April 29, 2022, Last downloaded: ClinicalTrials.gov processed this data on April 03, 2024, Last updated: April 03, 2024

Study ID:	NCT05353439 NCI-2022-03215 22-C-0005 10445
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PPN (Katalog-ID):	CTG000042137