bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTIM-41. ONCOLYTIC IMMUNOTHERAPY LINKS IMMUNOACTIVATION TO SUBJECT SURVIVAL IN PHASE I TRIAL OF RECURRENT GLIOBLASTOMA
Authors: Ling Alexander , Solomon Isaac , Nakashima Hiroshi , Santos Andres , Barone Francesca , Reardon David , Chiocca E Antonio 
Published: November 2023

Abstract
A “first-in-human” phase 1 trial of intralesional injection of CAN-3110, an immunotherapeutic oncolytic based on herpes simplex virus 1 (HSV1), was conducted in 41 subjects with recurrent high-grade glioma (rHGG). The impact of CAN-3110 on the tumor immune microenvironment was assessed using immunohistochemistry, multiplexed immunofluorescence, TCR-beta DNA sequencing, and bulk RNA sequencing of paired pre- and post-treatment samples. These analyses were combined with patient features to identify potential biomarkers of therapy response in rHGG. In IDH wild type recurrent glioblastoma (IDHwt rGBM) patients, post-treatment survival times were positively associated with positive pre-treatment HSV1 serology after controlling for additional covariates such as tumor volume, age, gender, CAN-3110 dose, etc. (HR = 0.16, p &lt; 0.001, n = 32, CoxPH). Positive HSV1 serology was also significantly associated with clearance of CAN-3110 from injected tumors. Interestingly, increased intratumoral CD8 and CD4 T cell numbers following treatment were positively associated with prolonged survival in HSV1 seropositive patients (p = 0.017 and 0.026, respectively), but not when analyses were conducted including HSV1 seronegative patients. Likewise, post-treatment immune expression signatures (such as for antitumor cytokines, T cell traffic, etc.) were more strongly associated with prolonged survival for HSV1 seropositive patients than for seronegative patients, and most assessed immune signatures only became associated with survival after CAN-3110 treatment. Extended survival was also associated with increased TCR-beta diversity following therapy in both the tumor and in PBMCs. Combined with a lack of observed dose-limiting toxicities and a median post-treatment survival of 14.2 months (95% CI: 9.5-15.7) in IDHwt rGBM patients with positive HSV1 serology, these data provide evidence that intralesional CAN-3110 treatment can instigate immune activation in a traditionally immunologically cold tumor and that this immune activation may influence survival time—particularly when patients have had prior exposure to HSV1. (clinicaltrials.gov NCT03152318).
CTNI-01. LONG-TERM RESULTS FROM A PHASE 1 TRIAL OF SPINE SBRT IN INOPERABLE PATIENTS WITH CORD COMPRESSION
Authors: Ghia Amol , Guha-Thakurta Nandita , Li Jing , McAleer Mary Frances , Briere Tina , Tatsui Claudio , Brown Paul , Beckham Thomas , Wang Chenyang , Yeboa D Nana , Chang Eric , Rhines Laurence 
Published: November 2023

Abstract

PURPOSE/OBJECTIVE
We seek to establish the feasibility of using spine stereotactic radiosurgery (SSRS) allowing for spinal cord dose constraint relaxation as the primary management of metastatic epidural spinal cord compression (MESCC) in inoperable patients monitoring for radiation myelopathy (RM) and radiographic local control (LC).

MATERIAL/METHODS
Patients with radiation naïve MESCC were enrolled on this prospective Phase 1 trial. Single fraction SSRS was delivered to a dose of 18 or 24 Gy. Spinal cord constraint relaxation was performed in sequential cohorts from an initial allowable Dmax cohort of 10 Gy up to 16 Gy only if tumor progression occurred without RM.

RESULTS
Thirty two patients enrolled on the trial of which 4, 12, 8 and 8 were in the 10 Gy, 12 Gy, 14 Gy and 16 Gy cord Dmax cohorts, respectively. At baseline, there were 10 sites with MESCC Grade 1B, 10 sites with Grade 1C, 9 sites with Grade 2, 2 sites with Grade 1A, and 1 site with Grade 3 disease. Of the 28 evaluable patients, the median overall survival was 32.3 months (range 5.8-122.6 mo). The 1-year and 5-year LC was 84.5% and 79.5%. The 2-year LC did not statistically differ between the 14-16 Gy cord Dmax combined cohorts and the 10-12 Gy cord Dmax combined cohorts (92.9% vs. 62.9%, p = 0.15). With a median clinical follow-up of 22.7 months (range 3-122.3 mo), there were no cases of RM including in the 13 patients who survived at least 3 years. In the cohort receiving a cord Dmax of 16 Gy, there were no cases of RM with a median follow-up of 18.6 mo (range 9.0-97.1 mo).

CONCLUSION
With long-term follow-up, these data demonstrate that SSRS is a safe and effective tool in patients with MESCC. Cord constraint relaxation may be considered in inoperable patients with MESCC.
CTNI-02. A LONGITUDINAL THERAPY RESPONSE MONITORING STUDY IN SUBJECTS WITH LEPTOMENINGEAL METASTASES USING CNSIDE COMPARED TO STANDARD OF CARE (CSF CYTOLOGY, CLINICAL EVALUATION, IMAGING)
Authors: Nagpal Seema , Youssef Michael , Beruti Sue , Gillis Laura , Gordon Kelly , Blouw Barbara , Kumthekar Priya 
Published: November 2023

Abstract
LM is diagnosed via clinical evaluation, neuroaxis neuroimaging (MRI brain and spine), and CSF cytology. These methods have limited sensitivity and specificity, and lack the ability to quantitatively measure the LM’s response to treatment. These hindrances create challenges in LM diagnosis and management for physicians. CNSide is a commercially available Laboratory Developed Test (LDT) that is analytically validated for the detection and characterization of tumor cells in the CSF, and run commercially in Biocept’s CLIA-certified, CAP-accredited laboratory. Physicians order CNSide testing at their discretion for patients that have a suspicion of LM. To evaluate the performance of CNSide for LM disease management in a controlled setting, Biocept is conducting a prospective, multi-center clinical study (FORESEE, NCT05414123) involving patients previously diagnosed with NSCLC or Breast Cancer and a suspicion or diagnosis of LM per standard of care (SOC) management, including clinical assessment, radiographic evaluation, and CSF cytology. At baseline and at designated time points throughout treatment, matched CSF samples will be analyzed in parallel with standard of care CSF cytology and CNSide at Biocept along with time matched neuroimaging and clinical evaluation. The primary end point of the trial is the proportion of decision points during LM treatment in which physicians indicated that CNSide aided in their decision making. Physicians will also indicate which component of the test aided in management, modeling other similar studies that measure the effect of serum biomarker results on clinical management of cancer. Secondary end points include diagnostic comparison to clinical evaluation, cytology, and radiographic results, and determining the sensitivity, specificity, PPV and NPV of CNSide in the detection of CSF tumor cells (cytology being the reference standard).
CTNI-04. PHASE I STUDY OF RADIATION THERAPY (RT) FOLLOWED BY INTRATHECAL (IT) TRASTUZUMAB/PERTUZUMAB IN THE MANAGEMENT OF HER2+ BREAST LEPTOMENINGEAL DISEASE (LMD)
Authors: Ahmed Kamran , Kumthekar Priya , Pina Yolanda , Kim Youngchul , DeJesus Michelle , Evernden Brittany , Oliver Daniel , Vogelbaum Michael A , Tran Nam , Liu James , Etame Arnold , Armaghani Avan , Costa Ricardo , Soyano Aixa , Lee Kimberley , Arrington John , Rosa Marilin , Soliman Hatem , Yu Hsiang-Hsuan Michael , Han Hyo , Forsyth Peter 
Published: November 2023

Abstract

BACKGROUND
IT trastuzumab is used in the management of HER2+ breast LMD. The monoclonal antibody pertuzumab is used with trastuzumab in the management of metastatic and localized HER2+ breast cancer.

METHODS
The study is a multi-institutional, phase I/II trial of RT followed by IT trastuzumab/pertuzumab. HER2+ LMD patients with a life expectancy &gt;8 weeks were eligible. Treatment was initiated with RT, whole brain and/or focal brain/spine RT followed by IT trastuzumab/pertuzumab. The dose of IT trastuzumab was fixed at 80 mg with a dose escalation of IT pertuzumab. An mTPI-2 design was used to determine the recommended phase II dose (RP2D). Each cycle was 4 weeks with 2x/week treatment in cycle 1, weekly in cycle 2, and every two weeks thereafter. Clinical trial information: NCT04588545.

RESULTS
A total of 9 patients were enrolled. Median age was 51 (range: 34-63). Seven patients (78%) were hormone receptor (HR)-/HER2+ and two were HR+/HER2+. Four dose cohorts were treated 10, 20, 40, each with one patient and 80 mg pertuzumab with six patients. Study therapy was well tolerated with no dose limiting toxicities identified. Toxicities at least partially attributable to study therapy included fatigue [grade 1 (n = 2); grade 2 (n = 1)], grade 1 extremity pain (n = 1), and grade 1 headaches (n = 1). Two patients were noted to have infected Ommaya reservoirs after which one patient resumed treatment while one patient stopped therapy after noting stable LMD for approximately 24 months. Median survival has not been reached with a 12 month OS of 86%. Best leptomeningeal response has been a partial response in 4 patients (44%) and stable disease in 5 patients (56%). Six patients continue study therapy currently.

CONCLUSIONS
Study therapy was well tolerated with a pertuzumab RP2D of 80 mg. Preliminary efficacy appears encouraging and continues to be assessed in the phase II portion.
CTNI-07. PHASE I STUDY OF PAXALISIB AND RADIOTHERAPY FOR CNS DISEASE HARBORING PI3K PATHWAY MUTATIONS: PILOT ANALYSIS OF CIRCULATING TUMOR DNA FOR PATIENT ELIGIBILITY CONFIRMATION AND POST-TREATMENT RESPONSE
Authors: Imber Brandon , Ravichandran Vignesh , Rao Pavitra , Casanova Hilary , Friend John , Simpson Jeremy , Pike Luke , Zinovoy Melissa , Mitchell Ryan , Chacko Christina , Kotecha Rupesh , Somai Somica , Boire Adrienne , Gavrilovic Igor , Piotrowski Anna , Wilcox Jessica , Malani Rachna , Young Robert , Offin Michael , Diamond Eli , Yang Jonathan 
Published: November 2023

Abstract

INTRODUCTION
Radiotherapy (RT) is effective for brain metastases (BM) or leptomeningeal disease (LMD), but disease control is poor for tumors harboring PI3K pathway alterations (PI3Kalt). We hypothesized that combining RT with paxalisib, a CNS-penetrant PI3K/mTOR inhibitor, offers therapeutic synergy. The role of plasma circulating tumor DNA (ctDNA) to confirm study eligibility and response monitoring is unclear.

METHODS
This is a multi-institutional, phase I trial of concurrent paxalisib and whole brain RT (30 Gy in 10 fractions, NCT04192981) for CNS disease. To establish eligibility, patients had documented PI3Kalt performed using institutional tumor targeted sequencing (MSK-IMPACT) of primary or metastatic tumors (eligibility sequencing). Plasma ctDNA was collected at baseline and 3-, 6- and 9-months post-treatment and sequenced using institutional plasma ctDNA targeted sequencing platform (MSK-ACCESS). Our objectives were to a) determine PI3Kalt concordance between eligibility sequencing and baseline ctDNA and b) analyze quantitative post-treatment plasma ctDNA dynamics.

RESULTS
Between 3/2020-5/2023, 15 patients were enrolled to receive daily paxalisib (45mg, n = 11 or 60mg, n = 4) and WBRT. Twelve were treated for BM and 3 for LMD. Eligibility sequencing was determined a median of 8.1months (range: 2.4-38.6) pre-study enrollment and the most common PI3Kalt were PIK3CA (n = 7), INPP4B (n = 2), INPPL1 (n = 1) and PIK3CG (n = 1), and PTEN copy number alterations (homdel n = 2). Baseline ctDNA was sequenced from 13/15 patients (18 samples: baseline = 13, 3-months = 4 and 6-months = 1). We confirmed 100% of PIK3CA mutations using baseline ctDNA. One breast cancer BM patient demonstrated significant variant allele frequency reduction from 50% (baseline) to 0.1% (3-months post-treatment) for two tracked PIK3CA mutations (p.E545K and p.A1066V), which correlated with a partial response per RANO-BM.

CONCLUSIONS
For patients on genomically-driven targeted therapy and RT combination trials, alterations detected using plasma ctDNA, especially PIK3CA, may be used to rapidly assess eligibility. Serial ctDNA collection may serve as a potential response biomarker with further validation.
CTNI-09. DOSE ESCALATION FOR NEOADJUVANT STEREOTACTIC RADIOSURGERY FOR LARGE BRAIN METASTASES: PHASE I RESULTS
Authors: Murphy Erin , Yang Kailin , Suh John , Yu Jennifer , Stevens Glen , Angelov Lilyana , Vogelbaum Michael A , Barnett Gene , Ahluwalia Manmeet , Neyman Gennady , Mohammadi Alireza , Chao Samuel 
Published: November 2023

Abstract

BACKGROUND
Surgical resection may be required for large and symptomatic brain metastases. Adjuvant radiotherapy or stereotactic radiosurgery (SRS) is needed to reduce local recurrence. Adjuvant radiosurgery has been associated with higher rates of leptomeningeal failure and radionecrosis. We conducted a phase I trial for brain metastases greater than 2 cm in size to determine the safety of preoperative SRS at escalating doses.

METHODS
Radiosurgery dose was escalated at 3 Gy increments starting with RTOG 90-05 dosing for 3 cohorts based on maximum tumor diameter: 18 Gy for &gt;2-3 cm, 15 Gy for &gt;3-4 cm, and 12 Gy &gt;4-6 cm. Dose limiting toxicity (DLT) was defined as grade III or greater acute toxicity. Patients underwent surgical resection within 2 weeks and were followed with imaging and physical evaluations every 3 months.

RESULTS
For tumor size &gt;2-3 cm, patients were enrolled up to the second dose level (21 Gy); for &gt;3-4 cm and &gt;4-6 cm cohorts the third dose level (21 Gy and 18 Gy, respectively) was reached. 35 patients were enrolled with 36 brain metastases treated with preoperative radiosurgery. There were 2 DLT (wound issues) in the &gt;3-4 cm arm at the third dose level and 1 DLT (hemorrhage) in the &gt;4-6 cm arm at the third dose level. The maximal tolerated SRS dose (MTD) for &gt;-2-3 cm arm was not reached, for &gt;3-4 cm arm was 18 Gy and for &gt;4-6 cm arm was 18 Gy. With a median follow-up of 64 months, the 6- and 12-month local control rates were 88.8% and 79.1%, respectively. The 2-year rate of LMD was 0%.

CONCLUSION
This Phase I preoperative SRS dose escalation trial found a MTD for brain metastases greater than 3 and up to 6 cm in size. The phase II trial will be conducted at the maximum tolerated SRS doses.
CTNI-17. APPLICATION OF THE GBM-X DATA PLATFORM TO ESTIMATE TREATMENT EFFECTS OF THE EXPERIMENTAL THERAPIES OF THE RANDOMIZED PHASE 2 INDIVIDUALIZED SCREENING TRIAL OF INNOVATIVE GLIOBLASTOMA THERAPIES
Authors: Rahman Rifaquat , Trippa Lorenzo , Fell Geoffrey , Lee Eudocia , Arrillaga-Romany Isabel , Touat Mehdi , Drappatz Jan , Welch Mary , Galanis Evanthia , Ahluwalia Manmeet , Colman Howard , Nabors Burt , Hepel Jaroslaw , Elinzano Heinrich , Schiff David , Chukwueke Ugonma , Beroukhim Rameen , Nayak Lakshmi , McFaline-Figueroa Jose Ricardo , Batchelor Tracy , Rinne Mikael , Kaley Thomas , Lu-Emerson Christine , Mellinghoff Ingo , Bi Wenya Linda , Arnaout Omar , Peruzzi Pier Paolo , Haas-Kogan Daphne , Tanguturi Shyam , Cagney Daniel , Aizer Ayal , Doherty Lisa , Santagata Sandro , Meredith David , Antonio Chiocca E , Reardon David , Alexander Brian , Ligon Keith , Wen Patrick 
Published: November 2023

Abstract

BACKGROUND
Leveraging external data has the potential to increase efficiency and precision of drug development in glioblastoma by complementing or replacing data from in-trial controls. We used an external control arm (ECA) to re-analyze data of the abemaciclib, neratinib and CC-115 arms of the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) trial.

METHODS
INSIGhT (NCT02977780) is an ongoing phase 2 adaptive platform trial in newly diagnosed MGMT unmethylated glioblastoma with a shared control arm of patients receiving radiation therapy with concurrent and maintenance temozolomide. The initial experimental arms (abemaciclib, neratinib, CC-115) have not shown a survival benefit relative to the shared control arm. We re-analyzed the experimental arm data and replaced the shared control arm with an ECA. The ECA was developed from a collection of trial datasets and real-world data available through the Glioblastoma External (GBM-X) Data Platform (). Propensity score matching was used to adjust for possible differences between pretreatment covariates (age, sex, resection, KPS) in the ECA and shared control arm. Cox proportional hazards models were used to estimate treatment effects.

RESULTS
On INSIGhT, patients were randomized to abemaciclib (n = 74), neratinib (n = 80), and CC-115 (n = 12). There were 687 unmethylated MGMT patients in the GBM-X ECA. After propensity score matching, there was no significant treatment effect associated with abemaciclib (HR 1.091, 95%CI:0.834-1.433, p = 0.536), neratinib (HR = 1.043, 95%CI:0.787-1.383, p = 0.770), or CC-115 (HR 1.088, 95%CI:0.834-1.433, p = 0.794) compared to the ECA.

CONCLUSION
In comparison to an ECA, there was no significant survival benefit with abemaciclib, neratinib and CC-115. Treatment effects estimates were similar to the primary analyses based on the original shared control arm of INSIGhT. The use of external control arms in early phase testing of new therapies is supported by our findings and could significantly reduce costs and time to conduct trials in newly diagnosed glioblastoma.
CTNI-21. PHASE I STUDY OF BTK INHIBITOR IBRUTINIB WITH TEMOZOLOMIDE AND RADIATION IN NEWLY-DIAGNOSED GLIOBLASTOMA (EQUILIBRIUM): FINAL TRIAL REPORT
Authors: Ahluwalia Manmeet , Ozair Ahmad , Khosla Atulya , Patel Neha , Elson Paul , Murphy Erin , Chao Samuel , Suh John , Stevens Glen , Peereboom David 
Published: November 2023

Abstract

BACKGROUND
Glioblastoma carries dismal prognosis for which novel therapeutics are urgently needed. Ibrutinib, an oral small molecule inhibitor of BTK, has been shown in preclinical models to inhibit cancer stem cells in glioblastoma. We sought to investigate safety and tolerability of ibrutinib for newly-diagnosed glioblastoma (nGBM).

METHODS
EQUILIBRIUM was a prospective, phase I trial conducted in nGBM patients with KPS ≥ 70% and normal organ function. Patients received standard of care chemoradiation plus ibrutinib in a 3 + 3 dose-escalation design (level 1: 420 mg daily, level 2: 560 mg daily, level -1: 280 mg daily). Primary study objective was to determine maximum tolerated dose (MTD) of ibrutinib in combination with radiotherapy (RT) of 60Gy over 6 weeks with/without 75 mg/m2 of temozolomide (TMZ) in MGMT methylated and unmethylated cohorts respectively. Secondary objective was to determine safety, overall survival (OS), and progression-free survival.

RESULTS
26 patients were enrolled, with 12 (46%) females. Median age was 61.5 years (range 76-22). 15 (58%) patients were MGMT methylated and 11 (42%) were unmethylated. Dose-limiting toxicities (DLTs) were observed at all dose levels of ibrutinib+RT arm. MTD of ibrutinib was noted to be 420 mg daily with RT+TMZ in methylated arm. In Ibrutinib+RT+TMZ arm, median cycles of TMZ were 4 (range 0-6) and of ibrutinib were 3 (range 0-26). Median OS for MGMT methylated arm was 26.0 (22.0-NA) months and for MGMT unmethylated cohort was 14.0 (8.54-NA) months. Median OS for EGFR-amplified was 29.5 (21.9-NA) months and for EGFR-non-amplified was 21.8 (16.6-NA) months. 2-year OS for MGMT methylated arm was 56% (34-95%) and for MGMT unmethylated arm was 2% (6-70%).

CONCLUSIONS
420 mg of Ibrutinib daily is safe and feasible with TMZ and RT for nGBM. Ibrutinib appears promising compared to historical outcomes in MGMT methylated patients. EGFR-amplified patients potentially derive significant benefit. Trial information: NCT03535350.
CTNI-26. EFFICACY AND SAFETY OF METFORMIN PLUS LOW-DOSE TEMOZOLOMIDE IN PATIENTS WITH RECURRENT OR REFRACTORY GLIOBLASTOMA: A RANDOMIZED, PROSPECTIVE, MULTICENTER, DOUBLE-BLIND, CONTROLLED, PHASE 2 TRIAL
Authors: Yoon Wan Soo , Chang Jong Hee , Kim Jeong Hoon , Kim Yu Jung , Jung Tae Young , Yoo Heon , Kim Se-Hyuk , Nam Do-Hyun , Kim Tae Min , Kim Se Hoon , Park Sung Hye , Lee Youn Soo , Kim Hyeon Woo , Hong Yong-Kil , Yang Seung Ho 
Published: November 2023

Abstract
Glioblastoma(GBM) has a poor prognosis after standard treatment. Recently, metformin has been shown to have an antitumor effect on glioma cells. We performed the first randomized prospective phase II clinical trial to investigate the clinical efficacy and safety of meformin in patients with recurrent or refractory GBM treated with low-dose temozolomide (TMZ). Included patients were randomly assigned to a control group [placebo plus low-dose TMZ (50mg/m2, daily) or and experimental group [metformin (1,000mg, 1,500mg, and 2,000mg per day during the 1st, 2nd, and 3rd week until disease progression, respectively) plus low-dose TMZ]. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), disease control rate, overall response rate, health-related quality of life, and safety. Among the 92 patients screened, 81 were randomly assigned to the control group (43 patients) or the experimental group (38 patients). Although the control group showed a longer median PFS, the difference between the two groups was not statistically significant (2.66 versus 2.3 months, p = 0.679). The median OS was 17.22 months (95% CI:12.19-21.68 months) in the experimental group and 7.69 months (95% CI: 5.16-22.67 months) in the control group, showing no significant difference by the log-rank test (HR:0.78; 95% CI:0.39-1.58; p = 0.473). The overall response rate and disease control rate were 9.3% and 46.5% in the control group and 5.3% and 47.3% in the experimental group, respectively. Although the metformin plus TMZ regimen was well tolerated, it did not confer a clinical benefit in patients with recurrent or refractory GBM.
CTNI-27. TRIAL IN PROGRESS A PHASE 2 STUDY OF BPM 31510 (AN OXIDIZED COQ10-LIPID CONJUGATE NANODISPERSION) WITH VITAMIN K AND STANDARD CHEMORADIATION IN NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Stocksdale Brian , Bertrand Sophie , Villanueva Eleanor , Naya Lewis , Molaie Donna , Lyng Arianne , Berman Brian , Vishnudas Vivek , Kiebish Michael , Gesta Stephane , Narain Niven , Recht Lawrence , Nagpal Seema 
Published: November 2023

Abstract
INTRODUCTION: BPM 31510 is a novel drug-lipid conjugate nanodispersion that significantly increases the bioavailability of ubidecarenone (oxidized CoQ10). Supraphysiological concentrations of CoQ10 have been shown to have a paradoxical pro-oxidant effect on a variety of malignant cells while not altering the metabolic phenotype in normal cells. Glioblastoma multiforme (GBM) is a metabolically active cancer that is reliant on mechanisms of redox homeostasis to avert reactive oxygen species (ROS)-triggered apoptosis. This trial investigates whether this susceptibility of GBM metabolism may be effectively targeted by the potentially synergistic combination of BPM 31510 and standard-of-care radiotherapy, a known producer of ROS. Early-phase trials of BPM 31510 have shown a favorable safety profile with primarily hepatotoxicity and coagulopathy, the latter of which is mitigated by co-administration of Vitamin K. TRIAL DESIGN: BPM 31510IV-11 (NCT04752813) is a single-arm multicenter phase 2 study of BPM 31510 + Vitamin K1 in combination with standard chemoradiation for newly diagnosed GBM. Eligible patients have GBM with no prior therapy, and those with recent hemorrhage, coagulopathy, or who require anticoagulation are excluded. BPM 31510 starts 2-4 weeks after biopsy or resection initially as monotherapy for 2 weeks followed by an additional 6 weeks in combination with temozolomide-based chemoradiation. To assess safety of BPM 31510 with concomitant chemoradiotherapy, this study begins with a dose confirmation phase and allows for one dose reduction in the event of a DLT. The starting dose of BPM 31510 is 110 mg/kg administered as a continuous infusion over 96-hours weekly. The primary endpoint is 6-month progression-free survival (PFS6) by RANO criteria. Secondary endpoints include overall survival and safety. Approximately 50 patients will be enrolled for 90% power in rejecting the null hypothesis of PFS6 ≤ 30%. The study is enrolling at two US sites with a third opening soon.