EPCT-16. A PHASE IB STUDY OF PTC596 IN CHILDREN WITH NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA AND HIGH GRADE GLIOMA
| Autor: | Natasha Pillay Smiley, John C. Breneman, Charles B. Stevenson, Eugene Hwang, Shiva Senthil Kumar, Patricia Baxter, Adam Lane, Xiao-Nan Li, Renee Doughman, Pius Maliakal, Maryam Fouladi, Clinton F. Stewart, Michelle Deutsch, Jim Leach, Sonia Romero, Rachid Drissi, Lan Gao |
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| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty business.industry medicine.medical_treatment Objective (goal) Phases of clinical research Newly diagnosed medicine.disease Early Phase Clinical Trials Radiation therapy Oncology Maximum tolerated dose Glioma AcademicSubjects/MED00300 Medicine AcademicSubjects/MED00310 Neurology (clinical) business High-Grade Glioma |
| Zdroj: | Neuro-Oncology |
| ISSN: | 1523-5866 1522-8517 |
| DOI: | 10.1093/neuonc/noaa222.138 |
| Popis: | BACKGROUND BMI-1 is highly expressed in DIPG. Downregulation leads to inhibition of cell proliferation, cell cycle signaling, self-renewal, telomerase expression, activity, and suppression of DIPG cell migration. Targeted inhibition of BMI-1 sensitizes DIPG cells to radiation and drug-induced DNA damage. PTC596 (formulated by PTC Therapeutics, Inc.) is a novel, orally available drug that inhibits microtubule polymerization, resulting in G2/M cell cycle arrest and post-translational modification of BMI-1 protein and reduced BMI-1 protein levels. OBJECTIVES: To estimate the maximum tolerated dose and describe dose limiting toxicities, pharmacokinetics and pharmacodynamics of PTC596 in children 3–21 years of age with newly diagnosed diffuse intrinsic pontine glioma and high-grade gliomas. METHODS PTC596 is administered twice per week orally during radiotherapy and as maintenance for up to two years. The starting dose of PTC596 was 200 mg/m2, with a subsequent dose level of 260mg/m2/dose. Pharmacokinetics are performed in Cycles 1 and 2. RESULTS This study is currently ongoing. Nine patients (7 with DIPG, 2 with HGG), 8 evaluable, have been enrolled. At dose level 1, 200 mg/m2, three evaluable patients were enrolled and experienced no DLTs. At dose level 2, among 5 evaluable patients, 2 experienced dose-limiting grade 4 neutropenia. PTC596 has been otherwise well tolerated. Five patients remain in Cycles 2–11. CONCLUSION This phase I trial is ongoing. PTC596 is tolerable at dose level 1. We are amending the protocol to introduce tablets that can be dissolved in liquid to allow enrollment of younger patients and those unable to swallow whole tablets. |
| Databáze: | OpenAIRE |
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