scholarly journals The Herby Study: a Phase 2 Open-Label, Randomized, Multicenter Study of Bevacizumab-Based Therapy in Pediatric Patients with Newly Diagnosed High-Grade Glioma

2014 ◽  
Vol 25 ◽  
pp. iv145
Author(s):  
J. Grill ◽  
D. Hargrave ◽  
P. Varlet ◽  
T. Jaspan ◽  
C. Jones ◽  
...  
Keyword(s):  
Multicenter Study ◽  
Pediatric Patients ◽  
High Grade Glioma ◽  
High Grade ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Open Label

scholarly journals Phase II, Open-Label, Randomized, Multicenter Trial (HERBY) of Bevacizumab in Pediatric Patients With Newly Diagnosed High-Grade Glioma

2018 ◽  
Vol 36 (10) ◽  
pp. 951-958 ◽  
Author(s):  
Jacques Grill ◽  
Maura Massimino ◽  
Eric Bouffet ◽  
Amedeo A. Azizi ◽  
Geoffrey McCowage ◽  
...  
Keyword(s):  
Adverse Events ◽  
Pediatric Patients ◽  
Group Versus ◽  
High Grade Glioma ◽  
Hazard Ratio ◽  
High Grade ◽  
Newly Diagnosed ◽  
Review Committee ◽  
Open Label ◽  
Risk Of Death

Purpose Bevacizumab (BEV) is approved in more than 60 countries for use in adults with recurrent glioblastoma. We evaluated the addition of BEV to radiotherapy plus temozolomide (RT+TMZ) in pediatric patients with newly diagnosed high-grade glioma (HGG). Methods The randomized, parallel group, multicenter, open-label HERBY trial ( ClinicalTrials.gov identifier: NCT01390948) enrolled patients age ≥ 3 years to ≤ 18 years with localized, centrally neuropathology-confirmed, nonbrainstem HGG. Eligible patients were randomly assigned to receive RT + TMZ (RT: 1.8 Gy, 5 days per week, and TMZ: 75 mg/m2 per day for 6 weeks; 4-week treatment break; then up to 12 × 28-day cycles of TMZ [cycle 1: 150 mg/m2 per day, days 1 to 5; cycles 2 to 12: 200 mg/m2 per day, days 1 to 5]) with or without BEV (10 mg/kg every 2 weeks). The primary end point was event-free survival (EFS) as assessed by a central radiology review committee that was blinded to treatment. We report findings of EFS at 12 months after the enrollment of the last patient. Results One hundred twenty-one patients were enrolled (RT+TMZ [n = 59]; BEV plus RT+TMZ [n = 62]). Central radiology review committee–assessed median EFS did not differ significantly between treatment groups (RT+TMZ, 11.8 months; 95% CI, 7.9 to 16.4 months; BEV plus RT+TMZ, 8.2 months; 95% CI, 7.8 to 12.7 months; hazard ratio, 1.44; P = .13 [stratified log-rank test]). In the overall survival analysis, the addition of BEV did not reduce the risk of death (hazard ratio, 1.23; 95% CI, 0.72 to 2.09). More patients in the BEV plus RT+TMZ group versus the RT+TMZ group experienced one or more serious adverse events (n = 35 [58%] v n = 27 [48%]), and more patients who received BEV discontinued study treatment as a result of adverse events (n = 13 [22%] v n = 3 [5%]). Conclusion Adding BEV to RT+TMZ did not improve EFS in pediatric patients with newly diagnosed HGG. Our findings were not comparable to those of previous adult trials, which highlights the importance of performing pediatric-specific studies.

scholarly journals PDCT-06. PHASE 1 STUDY OF ONC201 IN PEDIATRIC PATIENTS WITH H3 K27M-MUTANT HIGH GRADE GLIOMA OR NEWLY DIAGNOSED DIPG

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi201-vi201
Author(s):  
Sharon Gardner ◽  
Fernando Suarez ◽  
James M Stafford ◽  
Rohinton S. Tarapore ◽  
Krystal Merdinger ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Phase 1 ◽  
High Grade Glioma ◽  
High Grade ◽  
Newly Diagnosed ◽  
Phase 1 Study

ONC201 in previously irradiated pediatric H3 K27M-mutant glioma or newly diagnosed DIPG.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3619-3619
Author(s):  
Sharon L. Gardner ◽  
Carl Johannes Koschmann ◽  
Rohinton Tarapore ◽  
Jeffrey C. Allen ◽  
Wafik Tharwat Zaky ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Body Weight ◽  
Single Agent ◽  
High Grade Glioma ◽  
Biologically Active ◽  
High Grade ◽  
Newly Diagnosed ◽  
Preclinical Models ◽  
Open Label ◽  
The Impact

3619 Background: ONC201 is a first-in-class DRD2 antagonist and ClpP agonist that has demonstrated promising activity in high-grade glioma preclinical models and radiographic regressions with single agent ONC201 in recurrent H3 K27M-mutant glioma patients . The recommended phase 2 dose (RP2D) of 625mg ONC201 orally once a week has been established in adult patients as well tolerated and biologically active. ONC201 efficacy has been shown in high-grade glioma preclinical models and radiographic regressions with single agent ONC201 have been reported in adult recurrent H3 K27M-mutant glioma patients. We report results from the first Phase I pediatric clinical trial of ONC201. Methods: This open-label, multi-center trial for pediatric H3 K27M-mutant glioma or non-biopsied DIPG employed a 3+3 dose-escalation and dose-expansion design with 6 arms. Arms A and E, which have completed accrual, determined the RP2D of ONC201 using oral capsule and liquid formulations in post-radiation pediatric H3 K27M-mutant glioma patients ONC201, respectively. Arm B aims to determine the RP2D for ONC201 in combination with radiotherapy in patients with newly diagnosed DIPG. Arms C and D aim to measure intratumoral ONC201 concentrations in midline glioma patients and the impact of ONC201 on H3 K27M DNA levels in CSF, respectively. Arm F was recently opened to study ONC201 as a single agent in patients with progressive H3 K27M-mutant tumors (excluding DIPG and spinal cord tumors) following radiotherapy. After determining the RP2D, a dose-expansion cohort will evaluate the safety, radiographic response, and activity of ONC201. Results: An RP2D of weekly 625mg ONC201 scaled by body weight as a capsule or in liquid formulation was established in the primary endpoints of arms A, B and E alone or in combination with radiation, without incidence of dose-limiting toxicity (DLT). Pharmacokinetic profiles were similar to those observed in adults (T1/2: 8.4h; Tmax: 2.1h; Cmax: 2.3ug/mL; AUC0-tlast: 16.4ug/mL), with similar exposure across body weights. Conclusions: ONC201 was well tolerated without DLTs at the same adult RP2D scaled by body weight as monotherapy or in combination with radiotherapy in pediatric H3 K27M-mutant glioma patients. Further investigation of ONC201 to treat H3 K27M-mutant glioma and DIPG is warranted. Clinical trial information: NCT03416530 .

scholarly journals A prospective multicenter study of venous thromboembolism in patients with newly-diagnosed high-grade glioma: hazard rate and risk factors

2015 ◽  
Vol 124 (2) ◽  
pp. 299-305 ◽  
Author(s):  
Michael B. Streiff ◽  
Xiaobu Ye ◽  
Thomas S. Kickler ◽  
Serena Desideri ◽  
Jayesh Jani ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Multicenter Study ◽  
Hazard Rate ◽  
High Grade Glioma ◽  
High Grade ◽  
Newly Diagnosed ◽  
Prospective Multicenter 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.

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