A phase III study of radiation therapy plus carmustine with or without recombinant interferon-? in the treatment of patients with newly diagnosed high-grade glioma

Cancer ◽  
2001 ◽  
Vol 92 (2) ◽  
pp. 420-433 ◽  
Author(s):  
Jan C. Buckner ◽  
Paula J. Schomberg ◽  
William L. McGinnis ◽  
Terrence L. Cascino ◽  
Bernd W. Scheithauer ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
High Grade Glioma ◽  
Phase Iii ◽  
High Grade ◽  
Newly Diagnosed ◽  
Recombinant Interferon ◽  
Phase Iii Study

Vincristine (V), dactinomycin (A), and lower doses of cyclophosphamide (C) with or without radiation therapy for patients with newly diagnosed low-risk embryonal rhabdomyosarcoma (ERMS): A report from the Children’s Oncology Group (COG).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9509-9509 ◽  
Author(s):  
David Walterhouse ◽  
Alberto S. Pappo ◽  
Jane L Meza ◽  
John C. Breneman ◽  
Andrea Anita Hayes-Jordan ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Complete Response ◽  
Low Risk ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Group Iii ◽  
Group I ◽  
Phase Iii Study ◽  
Stage 1

9509 Background: Intergroup Rhabdomyosarcoma Study (IRS) trials showed improved survival with VAC compared with VA for patients with Stage 1 Group III (non-orbit) or Stage 3 Group I/II ERMS (see table). In COG ARST0331, we hypothesized that VA in combination with lower doses of C (total cumulative dose=4.8 g/m2) would produce the benefit of IRS-IV VAC with less toxicity for patients with Stage 1 Group III (non-orbit) or Stage 3 Group I/II low-risk ERMS. Methods: This single arm, non-inferiority, phase III study enrolled newly diagnosed patients with Stage 1 Group III (non-orbit) ERMS or Stage 3 Group I/II ERMS onto Subset 2. Therapy was 4 cycles of VAC followed by 12 cycles of VA over 46 weeks (total cumulative doses: V=54 mg/m2, A=21.6 mg/m2, C=4.8 g/m2). The radiation therapy dose was 36 Gy for Group IIA patients, 41.4 Gy for Group IIB/C patients, and 50.4 Gy for Group III patients. From 2004–2008 girls with Group III vaginal RMS did not receive radiotherapy if a complete response was achieved with chemotherapy with or without delayed resection. The primary endpoint was failure-free survival (FFS), and results were compared with a fixed expected outcome. Results: With a median follow-up of 3.0 yrs, we observed 16 failures vs. 7.8 expected failures. Estimated 3-yr FFS was 63% (95% CI: 46%, 75%) (n=60), and overall survival (OS) was 84% (95% CI: 68%, 93%). Estimated 3-yr FFS was 46% (95% CI: 23%, 67%) for girls with non-bladder genitourinary tract ERMS (n=21) and 75% (95% CI: 53%, 88%) for all other Subset 2 patients (n=39). Conclusions: We observed suboptimal FFS of patients with Subset 2 low-risk RMS using reduced total cyclophosphamide (4.8 g/m2). Results were complicated by the choice of no radiation therapy for girls with vaginal tumors. Future studies for low-risk RMS Subset 2 patients could investigate a dose of C between 4.8 and 26.4 g/m2 with VA and local radiotherapy. [Table: see text]

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

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS2577-TPS2577
Author(s):  
Katherine B. Peters ◽  
Adam Louis Cohen ◽  
Nicholas A. Butowski ◽  
John L. Villano ◽  
Pierre Giglio ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
White Matter ◽  
Cancer Therapy ◽  
Phase Ii ◽  
Functional Assessment ◽  
Phase Ii Study ◽  
High Grade Glioma ◽  
High Grade ◽  
Newly Diagnosed ◽  
Who Grade

TPS2577 Background: Patients diagnosed with malignant high-grade gliomas (WHO grade III-IV) experience significant morbidity and mortality associated with these cancers. While the mainstay of therapy for patients with newly diagnosed high-grade glioma is surgery followed by concurrent chemotherapy and radiation therapy (RT), the outcomes remain very poor. BMX-001 (MnTnBuOE-2-PyP5+) is a metalloporphyrin with differential action in response to radiation therapy and chemotherapy-induced oxidative stress. Early preclinical studies demonstrated BMX-001’s ability to act as a radioprotectant to healthy tissue such as a central nervous white matter and as a radiosensitizer to cancer cells, in particular, human glioblastoma xenografts. We evaluated the safety of BMX-001 in combination with concurrent RT and temozolomide (TMZ) in a phase I 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 II 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 include cognitive performance as assessed by standardized cognitive testing, bone marrow protection, safety and tolerability, progression-free survival, overall tumor response rate, and plasma pharmacokinetics. Exploratory endpoints are 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 II study has enrolled 64 of 160 high-grade glioma patients at six sites with future sites planned to be implemented. Clinical trial information: NCT02655601 .

Feasibility of Using Bevacizumab With Radiation Therapy and Temozolomide in Newly Diagnosed High-Grade Glioma

2008 ◽  
Vol 72 (2) ◽  
pp. 383-389 ◽  
Author(s):  
Ashwatha Narayana ◽  
John G. Golfinos ◽  
Ingeborg Fischer ◽  
Shahzad Raza ◽  
Patrick Kelly ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
High Grade Glioma ◽  
High Grade ◽  
Newly Diagnosed

Phase III comparative evaluation of PCNU and carmustine combined with radiation therapy for high-grade glioma.

1993 ◽  
Vol 11 (7) ◽  
pp. 1316-1321 ◽  
Author(s):  
R P Dinapoli ◽  
L D Brown ◽  
R M Arusell ◽  
J D Earle ◽  
J R O'Fallon ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
High Grade Glioma ◽  
Radical Resection ◽  
Phase Iii ◽  
Survival Duration ◽  
High Grade ◽  
Grade 3

PURPOSE We performed a randomized trial to compare survival distributions and toxicity of radiation therapy (RT) and PCNU with those of RT and carmustine (BCNU) in patients with malignant glioma. PATIENTS AND METHODS A total of 346 patients with histologically verified supratentorial grade 3 and grade 4 astrocytoma were studied. After surgery, patients were randomly assigned to receive RT 60 Gy in 30 fractions and either PCNU 100 mg/m2 or BCNU 200 mg/m2 every 7 weeks for 1 year and every 10 weeks for the second year. RT and chemotherapy were started within 72 hours of randomization and usually on the same day. Of 334 assessable patients, 72% had partial or radical resection and 71% had grade 4 tumors. Median age was 59 years, and 85% had performance scores of 0 to 2 (Eastern Cooperative Oncology Group [ECOG]). The follow-up duration of 51 living patients ranged from 10.3 to 63.2 months, with a median of 36.2 months. RESULTS The median survival duration in each group was 47 weeks, and median time to progression was 28 weeks. PCNU produced significantly more leukopenia and thrombocytopenia, whereas BCNU produced significantly more nausea, vomiting, and irritation. CONCLUSION PCNU has no therapeutic advantage at this dose and schedule and does not warrant further study as a single agent for patients with high-grade glioma.

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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