MRI changes in patients with newly diagnosed glioblastoma treated as part of a phase II trial with bavituximab, radiation, and temozolomide.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2546-2546
Author(s):  
Ina Ly ◽  
Jonathan Cardona ◽  
Kevin Lou ◽  
Andrew Beers ◽  
Ken Chang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Synergistic Effects ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Newly Diagnosed Glioblastoma ◽  
Tumor Region ◽  
Pre Treatment ◽  
Mri Changes

2546 Background: Glioblastoma and tumor endothelial cells express phosphatidylserine (PS), a highly immunosuppressive membrane phospholipid. Bavituximab – a chimeric monoclonal antibody – binds to β2-glycoprotein 1 (β2-GP1) to form a complex of β2-GP1 with PS, resulting in immune activation against tumor cells and anti-angiogenic effects. Phase I/II trials in other solid cancers demonstrated response rates up to 75% when bavituximab was given with cytotoxic chemotherapy. Pre-clinical data in glioblastoma models suggested synergistic effects of PS blockade, radiation, and temozolomide. Methods: 33 adult patients with IDH-wild-type, MGMT-methylated or -unmethylated newly diagnosed glioblastoma were enrolled in this phase II trial (NCT03139916) and received 6 weeks of chemoradiation, followed by 6 cycles of adjuvant temozolomide (C1-C6 aTMZ). Bavituximab (3 mg/kg) was given weekly, starting week 1 of chemoradiation, for 18 weeks with the option to continue if tolerated. Physiologic MRIs were performed pre-treatment, pre-C1, pre-C3, and pre-C5 aTMZ. Within the enhancing tumor region, median tumor Ktrans (reflecting vascular permeability) and relative cerebral blood flow (rCBF) were measured. Median percent changes during treatment were compared to pre-treatment values. Results: Median progression-free survival (mPFS) was 8 months. Based on a median overall survival (mOS) of 17.1 months, patients were categorized into above-median survivors (AMS) and below-median survivors (BMS). All patients had pre-treatment scans. 31 had evaluable pre-C1, 25 had pre-C3, and 7 had pre-C5 scans. Compared to BMS, AMS had a greater reuction in enhancing tumor volume and rCBF, and a greater increase in Ktrans during treatment (table). One patient remains on study; 23 patients have died. Bavituximab was well tolerated. Conclusions: mPFS and mOS in patients treated with bavituximab, radiation and temozolomide were comparable to standard chemoradiation and aTMZ. Lower rCBF in AMS may reflect decreased tumor perfusion while higher Ktrans could imply enhanced drug delivery to the tumor. Bavituximab induces changes in tumor vasculature that may improve survival in a subset of patients. Clinical trial information: NCT03139916 . [Table: see text]

scholarly journals NIMG-68. MRI CHANGES IN NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS TREATED AS PART OF A PHASE II TRIAL WITH BAVITUXIMAB, RADIATION, AND TEMOZOLOMIDE

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi191-vi191
Author(s):  
Ina Ly ◽  
Jonathan Cardona ◽  
Andrew Beers ◽  
Ken Chang ◽  
James Brown ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma ◽  
Mri Changes

scholarly journals Audencel Immunotherapy Based on Dendritic Cells Has No Effect on Overall and Progression-Free Survival in Newly Diagnosed Glioblastoma: A Phase II Randomized Trial

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 372 ◽  
Author(s):  
Johanna Buchroithner ◽  
Friedrich Erhart ◽  
Josef Pichler ◽  
Georg Widhalm ◽  
Matthias Preusser ◽  
...  
Keyword(s):  
Overall Survival ◽  
Dendritic Cells ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Severe Toxicity ◽  
Newly Diagnosed ◽  
Skin Reactions ◽  
Local Skin ◽  
Free Survival ◽  
Newly Diagnosed Glioblastoma

Dendritic cells (DCs) are antigen-presenting cells that are capable of priming anti-tumor immune responses, thus serving as attractive tools to generate tumor vaccines. In this multicentric randomized open-label phase II study, we investigated the efficacy of vaccination with tumor lysate-charged autologous DCs (Audencel) in newly diagnosed glioblastoma multiforme (GBM). Patients aged 18 to 70 years with histologically proven primary GBM and resection of at least 70% were randomized 1:1 to standard of care (SOC) or SOC plus vaccination (weekly intranodal application in weeks seven to 10, followed by monthly intervals). The primary endpoint was progression-free survival at 12 months. Secondary endpoints were overall survival, safety, and toxicity. Seventy-six adult patients were analyzed in this study. Vaccinations were given for seven (3–20) months on average. No severe toxicity was attributable to vaccination. Seven patients showed flu-like symptoms, and six patients developed local skin reactions. Progression-free survival at 12 months did not differ significantly between the control and vaccine groups (28.4% versus 24.5%, p = 0.9975). Median overall survival was similar with 18.3 months (vaccine: 564 days, 95% CI: 436–671 versus control: 568 days, 95% CI: 349–680; p = 0.89, harzard ratio (HR) 0.99). Hence, in this trial, the clinical outcomes of patients with primary GBM could not be improved by the addition of Audencel to SOC.

Phase II trial of sorafenib (S) and erlotinib (E) in unresectable pancreas cancer (UPC): Final results and correlative findings.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 191-191 ◽  
Author(s):  
Dana Backlund Cardin ◽  
Laura Williams Goff ◽  
Emily Chan ◽  
Melanie Holloway ◽  
Pamela McClanahan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Proportional Hazards ◽  
Phase Ii Trial ◽  
Synergistic Effects ◽  
Progression Free Survival ◽  
Outcome Data ◽  
Cox Proportional Hazards ◽  
Serum Samples ◽  
Pre Treatment

191 Background: The MAP kinase pathway plays a central role in PC pathogenesis. Blockade of this pathway at multiple levels using S and E is attractive mechanistically. S also targets VEGF receptors. Evidence suggests that dual blockade of both EGFR and VEGF pathways has potential for additive, if not synergistic, effects. This phase II trial was designed to evaluate the efficacy of the combination of S and E in patients (pts) with UPC. An exploratory correlative study analyzing pre-treatment serum samples using a proteomic mass-spectrometry test (VeriStrat), previously shown to correlate with outcomes in lung cancer pts treated with E or the combination of E and S, was performed to evaluate the possible clinical utility of the test in pts with UPC. Methods: Pts with UPC received S 400mg daily along with E 150mg daily as primarily second-line therapy (first-line was allowed). Primary endpoint was 8-week progression free survival (PFS) rate. Pre-treatment serum sample analysis by proteomic test was done blinded to clinical and outcome data; the endpoints were PFS and overall survival (OS). Difference between groups was assessed using log-rank p values; hazard ratios (HR) were obtained from Cox proportional hazards models. Results: Thirty-seven pts received study drugs and were included in the survival analysis. Eight-week PFS rate 0.47 (95% CI 0.32-0.67) did not meet the primary endpoint of a rate of ≥ 0.70. Thirty two pts were included in the correlative analysis. VeriStrat “Good” pts had superior PFS and OS compared to VeriStrat “Poor” pts (Table). Conclusions: This study did not meet the primary endpoint and this drug combination will not be further pursued. In this small retrospective analysis the proteomic classification was significantly associated with clinical outcomes (PFS and OS), meriting further evaluation. This will include a companion study to an ongoing phase I study evaluating gemcitabine, erlotinib and dasatinib in UPC (NCT01660971). Clinical trial information: NCT00837876. [Table: see text]

scholarly journals ATIM-41. PHASE II TRIAL OF A SURVIVIN VACCINE (SurVaxM) For Newly Diagnosed Glioblastoma

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi10-vi11 ◽  
Author(s):  
Manmeet Ahluwalia ◽  
David Reardon ◽  
Ajay Abad ◽  
William Curry ◽  
Eric Wong ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma

scholarly journals Safety and tolerability of asunercept plus standard radiotherapy/temozolomide in Asian patients with newly-diagnosed glioblastoma: a phase I study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kuo-Chen Wei ◽  
Peng-Wei Hsu ◽  
Hong-Chieh Tsai ◽  
Ya-Jui Lin ◽  
Ko-Ting Chen ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Progression Free Survival ◽  
Multicenter Trial ◽  
Newly Diagnosed ◽  
Open Label ◽  
Free Survival ◽  
Asian Patients ◽  
Newly Diagnosed Glioblastoma ◽  
Secondary Endpoints

AbstractAsunercept (company code APG101 [Apogenix AG]; company code CAN008 [CANbridge Pharmaceuticals]) is a novel glycosylated fusion protein that has shown promising effectiveness in glioblastoma. This Phase I study was initiated to evaluate the tolerability and safety of asunercept in combination with standard radiotherapy and temozolomide (RT/TMZ) in Asian patients with newly diagnosed glioblastoma. This was the Phase I portion of a Phase I/II open label, multicenter trial of asunercept plus standard RT/TMZ. Adults with newly-diagnosed glioblastoma received surgical resection followed by standard RT/TMZ plus asunercept 200 mg/week (Cohort 1) or 400 mg/week (Cohort 2) by 30-min IV infusion. The primary endpoint was the safety and tolerability of asunercept during concurrent asunercept and RT/TMZ; dose-limiting toxicities were observed for each dose. Secondary endpoints included pharmacokinetics (PK) and 6-month progression-free survival (PFS6). All patients (Cohort 1, n = 3; Cohort 2, n = 7) completed ≥ 7 weeks of asunercept treatment. No DLTs were experienced. Only one possibly treatment-related treatment emergent adverse event (TEAE), Grade 1 gingival swelling, was observed. No Grade > 3 TEAEs were reported and no TEAE led to treatment discontinuation. Systemic asunercept exposure increased proportionally with dose and showed low inter-patient variability. The PFS6 rate was 33.3% and 57.1% for patients in Cohort 1 and 2, respectively. Patients in Cohort 2 maintained a PFS rate of 57.1% at Month 12. Adding asunercept to standard RT/TMZ was safe and well tolerated in patients with newly-diagnosed glioblastoma and 400 mg/week resulted in encouraging efficacy.Trial registration NCT02853565, August 3, 2016.

Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. Digestive Group of French Federation of Cancer Centers.

1998 ◽  
Vol 16 (8) ◽  
pp. 2739-2744 ◽  
Author(s):  
Y Bécouarn ◽  
M Ychou ◽  
M Ducreux ◽  
C Borel ◽  
F Bertheault-Cvitkovic ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Free Survival ◽  
Duration Of Response ◽  
Grade 3 ◽  
Colorectal Cancer Patients ◽  
Peripheral Sensory

PURPOSE To evaluate the objective tumor response rate and safety profile of oxaliplatin when administered to patients with previously untreated metastatic colorectal adenocarcinoma. PATIENTS AND METHODS A total of 39 patients were entered onto this phase II trial. One patient was excluded for having had a second cancer, so the study was based on 38 patients. Patients were treated with oxaliplatin 130 mg/m2 as a 2-hour infusion on day 1, every 21 days. Patients were assessed for response every three courses. All clinical and radiologic data were reviewed by an external panel of experts, with their assessment being considered definitive. RESULTS Nine partial responses (PRs) were observed (response rate, 24.3%; 95% confidence interval, 11.8% to 41.2%). The median duration of response was 216+ days. Fifteen patients (40.5%) had stable disease and 13 (35.2%) had progressive disease. The median progression-free survival time for all patients was 126+ days (range, 21 to 447+). The main toxicity was peripheral sensory neuropathy. Grade 3 neurotoxicity (National Cancer Institute common toxicity criteria [NCI-CTC]) was reported in 13%. Hematologic and gastrointestinal toxicities were mild. The incidence of grade 3 neutropenia was 5.2%, while that of grade 3 or 4 thrombopenia was 7.9%. Vomiting (grade 3 or 4) occurred in 7.9% of patients and grade 3 diarrhea in 2.6%. CONCLUSION This phase II study provides clear evidence of the safety and efficacy of oxaliplatin monotherapy at this dose and schedule in patients with previously untreated metastatic colorectal carcinoma.

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