A phase 2 study of valproic acid and radiation, followed by maintenance valproic acid and bevacizumab in children with newly diagnosed diffuse intrinsic pontine glioma or high‐grade glioma

2020 ◽  
Vol 67 (6) ◽  
Author(s):  
Jack Meng‐Fen Su ◽  
Jeffrey C. Murray ◽  
Rene Y. McNall‐Knapp ◽  
Daniel C. Bowers ◽  
Shafqat Shah ◽  
...  
Keyword(s):  
Valproic Acid ◽  
High Grade Glioma ◽  
Diffuse Intrinsic Pontine Glioma ◽  
High Grade ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Pontine Glioma ◽  
Phase 2 Study

Phase 2 trial of newly diagnosed high-grade glioma treated with concurrent radiation therapy, temozolomide, and BMX-001.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS2069-TPS2069
Author(s):  
Katherine B. Peters ◽  
John L. Villano ◽  
Nicholas A. Butowski ◽  
Adam Louis Cohen ◽  
Joe Sammy Mendez ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Cancer Therapy ◽  
Functional Assessment ◽  
High Grade Glioma ◽  
High Grade ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Who Grade ◽  
Phase 2 Study ◽  
Patient Reported

TPS2069 Background: High-grade gliomas (WHO grade III-IV) patients experience marked morbidity and mortality. While the standard of care for newly diagnosed high-grade glioma patients is surgery followed by concurrent chemotherapy and radiation therapy (RT), the outcomes remain poor. BMX-001 (MnTnBuOE-2-PyP5+) is a metalloporphyrin with differential action in response to radiation therapy and chemotherapy-induced oxidative stress. As shown in preclinical evaluations, BMX-001, when used with radiation, can protect normal, healthy tissues and augment cell kill in malignant cancer cells, notably, human glioblastoma xenografts. We evaluated the safety of BMX-001 in combination with concurrent RT and temozolomide (TMZ) in a phase 1 study of newly diagnosed high-grade glioma patients and we found that BMX-001 is safe and well-tolerated in this population. The maximum tolerated dose of BMX-001 during concurrent RT and TMZ was determined to be 28 mg delivered subcutaneously (SC) followed by 16 biweekly SC doses at 14 mg (Peters et al., Neuro-Oncology 2018). Methods: For this multi-site, open-label, phase 2 study (NCT02655601), we will randomize approximately 160 patients 1:1 to concurrent RT and TMZ with BMX-001 versus concurrent RT and TMZ alone. Key eligibility criteria include newly diagnosed histologically confirmed high-grade glioma (WHO III-IV), 18 ≥ years, and Karnofsky performance status ≥ 70%. The primary endpoint is overall survival. Secondary endpoints are objective cognitive performance, bone marrow protection, safety and tolerability, progression-free survival, overall tumor response rate, and plasma pharmacokinetics. Exploratory endpoints are patient-reported outcomes of health-related quality of life (as assessed by Functional Assessment of Cancer Therapy–Brain, Functional Assessment of Cancer Therapy-Cognition, and Functional Assessment of Chronic Illness Therapy-Fatigue), qualitative hair loss, and white matter integrity (as measured by MRI diffusion tensor/susceptibility imaging). Since November 2018, this phase 2 study has enrolled 147 of 160 high-grade glioma patients at nine sites in US. Clinical trial information: NCT02655601.

scholarly journals HGG-15. PHASE 2 NESTED COHORT STUDY OF DEPATUXIZUMAB MAFODOTIN IN CHILDREN WITH HIGH GRADE GLIOMA AND DIFFUSE INTRINSIC PONTINE GLIOMA WITH EGFR AMPLIFICATION

2018 ◽  
Vol 20 (suppl_2) ◽  
pp. i91-i92
Author(s):  
Martin van den Bent ◽  
Winand Dinjens ◽  
Vassilis Golfinopoulos ◽  
Peter Ansell ◽  
Fiona Dungey ◽  
...  
Keyword(s):  
Cohort Study ◽  
High Grade Glioma ◽  
Diffuse Intrinsic Pontine Glioma ◽  
High Grade ◽  
Phase 2 ◽  
Pontine Glioma ◽  
Egfr Amplification

scholarly journals EPCT-16. A PHASE IB STUDY OF PTC596 IN CHILDREN WITH NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA AND HIGH GRADE GLIOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii306-iii307
Author(s):  
Natasha Pillay Smiley ◽  
Patricia Baxter ◽  
Shiva Kumar ◽  
Eugene Hwang ◽  
John Breneman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dose Level ◽  
Diffuse Intrinsic Pontine Glioma ◽  
High Grade ◽  
Newly Diagnosed ◽  
Post Translational Modification ◽  
Pontine Glioma ◽  
M Cell ◽  
Drug Induced ◽  
Level 1

Abstract 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.

scholarly journals HG-122EFFECTS OF THE XPO1 INHIBITOR SELINEXOR ON THE NF-κB PATHWAY IN HIGH-GRADE GLIOMA AND DIFFUSE INTRINSIC PONTINE GLIOMA

2016 ◽  
Vol 18 (suppl 3) ◽  
pp. iii76.2-iii76
Author(s):  
John DeSisto ◽  
Patrick Flannery ◽  
Trinayan Kashyap ◽  
Andrew Kung ◽  
Sujatha Venkataraman ◽  
...  
Keyword(s):  
High Grade Glioma ◽  
Diffuse Intrinsic Pontine Glioma ◽  
High Grade ◽  
Pontine Glioma
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