A Study to Evaluate the Safety of 2-OHOA Added to Standard of Care in Newly-diagnosed Glioblastoma Patients

2019 ◽  
Author(s):  
Keyword(s):  
Standard Of Care ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma

scholarly journals A Review of Newly Diagnosed Glioblastoma

2021 ◽  
Vol 10 ◽  
Author(s):  
Bryan Oronsky ◽  
Tony R. Reid ◽  
Arnold Oronsky ◽  
Navjot Sandhu ◽  
Susan J. Knox
Keyword(s):  
Brain Tumor ◽  
Surgical Resection ◽  
Standard Of Care ◽  
Newly Diagnosed ◽  
Current Standard ◽  
Genetic Characteristics ◽  
Dismal Prognosis ◽  
Newly Diagnosed Glioblastoma ◽  
Temozolomide Chemotherapy

Glioblastoma is an aggressive and inevitably recurrent primary intra-axial brain tumor with a dismal prognosis. The current mainstay of treatment involves maximally safe surgical resection followed by radiotherapy over a 6-week period with concomitant temozolomide chemotherapy followed by temozolomide maintenance. This review provides a summary of the epidemiological, clinical, histologic and genetic characteristics of newly diagnosed disease as well as the current standard of care and potential future therapeutic prospects.

CTNI-19. CONCURRENT CHEMORADIATION AND TUMOR TREATING FIELDS (TTFields, 200 kHz) FOR PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA MAY INCREASE THE RATE OF DISTANT RECURRENCE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi63-vi63
Author(s):  
Ayesha S Ali ◽  
Muneeb Niazi ◽  
Voichita Bar-Ad ◽  
Maria Werner-Wasik ◽  
David Andrews ◽  
...  
Keyword(s):  
Radiation Treatment ◽  
Synergistic Effects ◽  
Secondary Analysis ◽  
Standard Of Care ◽  
Distant Recurrence ◽  
Concurrent Chemoradiation ◽  
Newly Diagnosed ◽  
Current Standard ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma

Abstract INTRODUCTION: Current standard of care for glioblastoma (GBM) includes concurrent chemoradiation and maintenance temozolomide (TMZ) along with Tumor Treating Fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. Secondary analysis of EF14 trial demonstrated TTFields treatment may increase the rate of distant recurrence. We report our experience evaluating areas of progression in our pilot clinical trial of concurrent chemoradiation with TTFields. METHODS: This is a single arm pilot study (clinicaltrials.gov Identifier: NCT03477110). Adult patients (age ≥ 18 years) with KPS ≥ 60 with newly diagnosed GBM were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions), standard concurrent TMZ (75 mg/m2 daily), and TTFields. Maintenance therapy included standard TMZ and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. Incidence and location of progression was documented. Distant recurrence was defined as recurrence more than 2 cm from primary enhancing lesion. RESULTS: A total of 30 patients were enrolled on the trial. Twenty were male, and ten were female, with median age 58 years (19-77 years). Median KPS was 90 (70-100). Median follow-up was 11.6 months (1.7-22.1 months). Twenty (66.7%) patients had an unmethylated MGMT promotor status and ten (33.3%) patients had a methylated promoter status. Twenty patients (66.7%) had progression, with median PFS of 9.1 months (range 1.6 to 12.9 months). Five patients (26%) of patient presented with distant recurrence, with median distance from primary lesion of 5.1 cm (2.26-9.12 cm). One infratentorial progression was noted. Another patient transferred care and location of progression is unknown. CONCLUSIONS: Concurrent chemoradiation with TTFields for patients with newly diagnosed glioblastoma may have increased incidence of distant recurrence. This finding is suggestive of improved local control of primary site. Further data are needed to validate this finding.

Scalp-sparing radiation with concurrent temozolomide and tumor treating fields (SPARE) for patients with newly diagnosed glioblastoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2056-2056
Author(s):  
Ryan C Miller ◽  
Andrew Jehyun Song ◽  
Ayesha Ali ◽  
Voichita C Bar-Ad ◽  
Nina Leyson Martinez ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Radiation Treatment ◽  
Synergistic Effects ◽  
Standard Of Care ◽  
Treatment Interruption ◽  
Newly Diagnosed ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma ◽  
Dose Constraints ◽  
Topical Medications

2056 Background: Standard of care for patients with newly diagnosed glioblastoma includes concurrent chemoradiation and maintenance temozolomide with Tumor Treating Fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. We report our clinical trial evaluating safety and tolerability of scalp-sparing radiation with concurrent temozolomide and TTFields. Methods: This is a single arm pilot study. Adult patients (age ≥ 18 years) with newly diagnosed glioblastoma and a KPS of ≥ 60 were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions) with temozolomide (75 mg/m2 daily) and TTFields (200 kHz). Maintenance therapy included temozolomide and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. The primary endpoint was safety and toxicity of TTFields concurrent with chemoradiation in patients with newly diagnosed glioblastoma. Results: A total of 30 patients were enrolled in the trial. Twenty were male and ten were female, with a median age of 58 years (range 19 to 77 years). Median KPS was 90 (range 70 to 100). Median follow-up was 8.9 months (range 1.6 to 21.4 months). Twenty (66.7%) patients had unmethylated MGMT promotor status and ten (33.3%) patients had methylated promoter status. Median time from surgery to radiation was 34 days (26 to 49 days). Scalp dose constraints were achieved for all patients, with the mean dose having a median value of 8.3 Gy (range 4.3 to 14.8 Gy), the D20cc median was 26.1 Gy (range 17.7 to 42.8 Gy), and the D30cc median was 23.5 Gy (range 14.8 to 35.4 Gy). Skin adverse events (AEs; erythema, dermatitis, irritation, folliculitis) were noted in 83.3% of patients, however, these were limited to Grade 1 or 2 events, which resolved spontaneously or with topical medications. No patient had radiation treatment interruption due to skin AEs. Other Grade 1 events included pruritus (33.3%), fatigue (30%), nausea (13.3%), headache (10%), dizziness (6.7%), and cognitive impairment (3.3%). Other Grade 2 events included headache (3.3%). Nineteen patients (63.3%) had progression, with a median PFS of 7.6 months (range 1.6 to 12.7 months). Overall survival was not reached. Conclusions: Concurrent TTFields (200 kHz) with scalp-sparing chemoradiation is a safe and feasible treatment option with limited toxicity. Future randomized prospective trials are warranted to define therapeutic advantages of concurrent TTFields with chemoradiation. Clinical trial information: NCT03477110.

RTID-05. THE MULTI-ARM GLIOBLASTOMA AUSTRALASIA (MAGMA) TRIAL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi193-vi194
Author(s):  
Benjamin Kong ◽  
Hao-Wen Sim ◽  
Eng-Siew Koh ◽  
Hui Gan ◽  
Elizabeth H Barnes ◽  
...  
Keyword(s):  
Data Collection ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Current Standard ◽  
Future Design ◽  
Multiple Treatment ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND Survival outcomes for patients with newly diagnosed glioblastoma have not changed significantly since the introduction of concurrent temozolomide with post-surgical radiation followed by adjuvant temozolomide. METHODS Multi-Arm Glioblastoma Australasia (MAGMA) is a recently initiated phase III multi-arm, multi-centre randomized trial for patients with newly diagnosed glioblastoma, led by the Australian Cooperative Trials Group for Neuro-Oncology (COGNO), that will concurrently test multiple treatment questions. Initially, a partial factorial design will be implemented to compare the current standard of care with either or both of (1) neoadjuvant temozolomide and (2) aduvant temozolomide continued beyond six months until progression. MAGMA will transition to a multi-arm multi-stage (MAMS) design as additional tratment question are introduced. Treatment allocation to each question will be balanced (1:1) using minimisation over several stratification factors, including study site, age, IDH-mutation status, surgical extent and randomization to the prior treatment question(s). The primary outcome is overall survival. Secondary outcomes include progression-free survival (measured by mRANO), time to first non-temozolomide systemic treatment, clinically significant toxicity as measured by Grade 2/4 adverse events, and health-related quality of life measures. Parsimonious data collection and a streamlined assessment schedule have been incorporated to mitigate the burden of data collection (such as low grade toxicity from temozolomide), and to encourage participation in regional and rural settings. A consortium model has been adopted to foster neuro-oncology expertise and infrastructure and share academic credit and future design opportunities. PROGRESS Recruitment commenced in September 2020. To date, 60 patients have been recruited from an initial sample size target of 250 patients for each of these initial two treatment questions. Of these 60 patients, 45 have been randomized in Question 1 (neoadjuvant chemotherapy) whilst 50 randomized in Question 2 (prolonged adjuvant chemotherapy). To date, 14 of the 27 intended sites are open to recruitment.

CTNI-35. UPDATE ON THE FEASIBILITY STUDY OF OKN-007 IN COMBINATION WITH TEMOZOLOMIDE AND RADIATION IN NEWLY DIAGNOSED GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi67-vi67
Author(s):  
James Battiste ◽  
Deborah Wright ◽  
Chad Glenn ◽  
Ian Dunn ◽  
Ozer Algan ◽  
...  
Keyword(s):  
Treatment Plan ◽  
Maintenance Phase ◽  
Standard Of Care ◽  
The Novel ◽  
Newly Diagnosed ◽  
Anti Cancer ◽  
Safety Parameters ◽  
Newly Diagnosed Glioblastoma ◽  
Cancer Agent ◽  
Dose Limiting Toxicity

Abstract BACKGROUND Temozolomide (TMZ) with concurrent radiation is the traditional standard of care for newly diagnosed glioblastoma. Unfortunately, this combination has limited efficacy and resistance can render TMZ ineffective. The novel anti-cancer agent OKN-007 plus TMZ increased survival in preclinical studies. Therefore, we initiated a phase Ib/feasibility clinical trial (NCT03587038) of OKN-007 in combination with TMZ and radiation therapy (RT). We report the safety and tolerability findings of this trial in-progress. METHODS Adults with newly-diagnosed GBM were eligible. OKN-007 was administered by IV at 60 mg/kg. There were three treatment phases: Concomitant, Pre-Maintenance, and Maintenance. In the Concomitant Phase, patients received OKN-007 three times per week (Cohort A) or five times per week (Cohort B); all patients receive TMZ at 75 mg/m2 daily and RT at 60 Gy over 30 fractions. In the 28-day Pre-Maintenance Phase, all patients receive OKN-007 thrice weekly. In the Maintenance Phase (MP), comprising up to eighteen 28-day cycles, TMZ was dosed at 150-200 mg/m2 on days 1-5 of each cycle for six cycles. OKN-007 was administered thrice weekly for six cycles, then twice weekly for three cycles, then once weekly for nine cycles. Each cohort was evaluated for safety with 3-6 patients followed by an expansion of cohorts if safety parameters were met. RESULTS Three patients completed Cohort A without dose-limiting toxicity (DLT). In Cohort B, two DLT’s (hematologic toxicities deemed to be related to TMZ) occurred, and this cohort was stopped. Currently, median PFS and OS have not been reached due to lack of events, but preliminary data indicate improved median PFS and OS compared to standard of care. CONCLUSIONS The treatment plan appears safe and well-tolerated at the Cohort A combination dosing level and may increase favorable treatment outcomes suggesting that the OKN-007 warrants further study.

CTIM-04. BIOMARKER IMMUNE CORRELATES IN NEWLY DIAGNOSED GLIOBLASTOMA (GBM) TREATED WITH ATEZOLIZUMAB IN COMBINATION WITH TEMOZOLOMIDE (TMZ) AND RADIATION

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi49-vi49
Author(s):  
Shiao-Pei Weathers ◽  
Mark Knafl ◽  
Edwin Parra ◽  
Sharia Hernandez ◽  
Luisa Solis ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Standard Of Care ◽  
Predictive Biomarker ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Newly Diagnosed ◽  
Immune Correlates ◽  
Newly Diagnosed Glioblastoma ◽  
Checkpoint Inhibitor Therapy ◽  
Pre Treatment

Abstract BACKGROUND Checkpoint inhibitor therapy has demonstrated overall limited efficacy in the treatment of GBM. Mechanisms of resistance to checkpoint blockade need to be better elucidated. Analysis of the tumor microenvironment is critical to identify correlates of response to immune checkpoint blockade. 60 newly diagnosed GBM patients unselected for MGMT status underwent treatment with concurrent atezolizumab with radiation therapy and TMZ followed by adjuvant atezolizumab and TMZ (NCT03174197). Clinical data has been reported previously. METHODS Tissue image immunoprofiling was conducted using 2 multiplex immunofluorescence (mIF) panels against; CD3, CD8, PD-1, PD-L1, Granzyme B, FOXP3, CD45RO, CD68, and GFAP antibodies. PDL-1 (Clone SP263) malignant cells expression was assessed by immunohistochemistry. Correlations between mIF biomarkers co-expressions, IHC PD-L1, and clinical outcome including OS, radiographic response, and PFS were evaluated. RESULTS Of 60 patients enrolled, image immunoprofiling was performed successfully on pre-treatment tissue in 48 patients. 20 of 60 patients underwent re-resection for suspected recurrent disease of which 10 patients had immunoprofiling performed successfully on pre and post treatment samples. An analysis of CD3CD8+ cytotoxic T lymphocytes was consistent with prior work, showing no or relatively low levels at baseline, and no association with clinical outcome. PDL-1 expression by IHC, at thresholds of >1% or >5%, was not associated with clinical outcome. Tumors with a higher number of GFAP-expressing cancer cells had a significantly lower tumor response (p< 0.05) and median OS (430 vs. 799 days, p< 0.01). CONCLUSIONS For newly diagnosed GBM patients treated with standard of care radiation and temozolomide in combination with atezolizumab, T-cell levels and PDL-1 expression were not predictive of outcome. GFAP may represent a novel predictive biomarker of overall survival. Ongoing studies to evaluate the gut microbiome and tumor genomic (WES, CNA) and transcriptomic (RNAseq) features of these and matched tumors are underway.

Health-Related Quality of Life in a Randomized Phase III Study of Bevacizumab, Temozolomide, and Radiotherapy in Newly Diagnosed Glioblastoma

2015 ◽  
Vol 33 (19) ◽  
pp. 2166-2175 ◽  
Author(s):  
Martin J.B. Taphoorn ◽  
Roger Henriksson ◽  
Andrew Bottomley ◽  
Timothy Cloughesy ◽  
Wolfgang Wick ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Standard Of Care ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Point Change ◽  
Free Survival ◽  
Related Quality ◽  
Health Related ◽  
Newly Diagnosed Glioblastoma

Purpose As glioblastoma progresses, patients experience a decline in health-related quality of life (HRQoL). Delaying this decline is an important treatment goal. In newly diagnosed glioblastoma, progression-free survival was prolonged when bevacizumab was added to radiotherapy plus temozolomide (RT/TMZ) versus placebo plus RT/TMZ (phase III AVAglio study; hazard ratio, 0.64; 95% CI, 0.55 to 0.74; P < .001). To ensure that addition of bevacizumab to standard-of-care therapy was not associated with HRQoL detriment, HRQoL assessment was a secondary objective. Patients and Methods Patients completed European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and BN20 at each tumor assessment (Appendix Table A1 , online only). Raw scores were converted to a 100-point scale and mean changes from baseline scores were evaluated (stable: < 10-point change; clinically relevant deterioration/improvement: ≥ 10-point change). Deterioration-free survival was the time to deterioration/progression/death; time to deterioration was the time to deterioration/death. Results Most evaluable patients who had not progressed (> 74%) completed all HRQoL assessments for at least 1 year of treatment, and almost all completed at least one HRQoL assessment at baseline (98.3% and 97.6%, bevacizumab and placebo arms, respectively). Mean changes from baseline did not reach a clinically relevant difference between arms for most items. HRQoL declined at progression in both arms. The addition of bevacizumab to RT/TMZ resulted in statistically longer (P < .001) deterioration-free survival across all items. Time to deterioration was not statistically longer in the placebo plus RT/TMZ arm (v bevacizumab) for any HRQoL item. Conclusion The addition of bevacizumab to standard-of-care treatment for newly diagnosed glioblastoma had no impact on HRQoL during the progression-free period.

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