scholarly journals A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas

2016 ◽  
Vol 124 (5) ◽  
pp. 1300-1309 ◽  
Author(s):  
Darryl Lau ◽  
Shawn L. Hervey-Jumper ◽  
Susan Chang ◽  
Annette M. Molinaro ◽  
Michael W. McDermott ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Fluorescence Intensity ◽  
Aminolevulinic Acid ◽  
Correlation Coefficients ◽  
Phase Ii Clinical Trial ◽  
High Grade ◽  
Predictive Values ◽  
High Grade Gliomas ◽  
Grade 3

OBJECT There is evidence that 5-aminolevulinic acid (ALA) facilitates greater extent of resection and improves 6-month progression-free survival in patients with high-grade gliomas. But there remains a paucity of studies that have examined whether the intensity of ALA fluorescence correlates with tumor cellularity. Therefore, a Phase II clinical trial was undertaken to examine the correlation of intensity of ALA fluorescence with the degree of tumor cellularity. METHODS A single-center, prospective, single-arm, open-label Phase II clinical trial of ALA fluorescence-guided resection of high-grade gliomas (Grade III and IV) was held over a 43-month period (August 2010 to February 2014). ALA was administered at a dose of 20 mg/kg body weight. Intraoperative biopsies from resection cavities were collected. The biopsies were graded on a 4-point scale (0 to 3) based on ALA fluorescence intensity by the surgeon and independently based on tumor cellularity by a neuropathologist. The primary outcome of interest was the correlation of ALA fluorescence intensity to tumor cellularity. The secondary outcome of interest was ALA adverse events. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and Spearman correlation coefficients were calculated. RESULTS A total of 211 biopsies from 59 patients were included. Mean age was 53.3 years and 59.5% were male. The majority of biopsies were glioblastoma (GBM) (79.7%). Slightly more than half (52.5%) of all tumors were recurrent. ALA intensity of 3 correlated with presence of tumor 97.4% (PPV) of the time. However, absence of ALA fluorescence (intensity 0) correlated with the absence of tumor only 37.7% (NPV) of the time. For all tumor types, GBM, Grade III gliomas, and recurrent tumors, ALA intensity 3 correlated strongly with cellularity Grade 3; Spearman correlation coefficients (r) were 0.65, 0.66, 0.65, and 0.62, respectively. The specificity and PPV of ALA intensity 3 correlating with cellularity Grade 3 ranged from 95% to 100% and 86% to 100%, respectively. In biopsies without tumor (cellularity Grade 0), 35.4% still demonstrated ALA fluorescence. Of those biopsies, 90.9% contained abnormal brain tissue, characterized by reactive astrocytes, scattered atypical cells, or inflammation, and 8.1% had normal brain. In nonfluorescent (ALA intensity 0) biopsies, 62.3% had tumor cells present. The ALA-associated complication rate among the study cohort was 3.4%. CONCLUSIONS The PPV of utilizing the most robust ALA fluorescence intensity (lava-like orange) as a predictor of tumor presence is high. However, the NPV of utilizing the absence of fluorescence as an indicator of no tumor is poor. ALA intensity is a strong predictor for degree of tumor cellularity for the most fluorescent areas but less so for lower ALA intensities. Even in the absence of tumor cells, reactive changes may lead to ALA fluorescence.

scholarly journals ATCT-21A PROSPECTIVE PHASE II CLINICAL TRIAL OF 5-AMINOLEVULINIC ACID TO CORRELATE INTRAOPERATIVE FLUORESCENCE INTENSITY WITH HISTOLOGIC CELLULARITY

2015 ◽  
Vol 17 (suppl 5) ◽  
pp. v6.1-v6
Author(s):  
Darryl Lau ◽  
Shawn Hervey-Jumper ◽  
Susan Chang ◽  
Annette Molinaro ◽  
Michael McDermott ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Fluorescence Intensity ◽  
Aminolevulinic Acid ◽  
Phase Ii Clinical Trial ◽  
Prospective Phase ◽  
Intraoperative Fluorescence

scholarly journals AT-46 * VORINOSTAT AND BEVACIZUMAB FOR RECURRENT HIGH-GRADE GLIOMA: INTERIM ANALYSIS OF A PHASE II CLINICAL TRIAL

2014 ◽  
Vol 16 (suppl 5) ◽  
pp. v18-v18
Author(s):  
K. Peters ◽  
D. Reardon ◽  
D. Randazzo ◽  
S. Dutton ◽  
A. Edwards ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Interim Analysis ◽  
High Grade Glioma ◽  
Phase Ii Clinical Trial ◽  
High Grade

Use of serum and tissue biomarker analysis embedded in a phase II clinical trial of cytarabine in castration-refractory prostate cancer to investigate prostate cancer biology.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 59-59
Author(s):  
S. Niraula ◽  
U. Emmeneger ◽  
L. Adams ◽  
I. Tannock ◽  
S. S. Sridhar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Cancer Biology ◽  
Target Therapy ◽  
Phase Ii Clinical Trial ◽  
Mrna Levels ◽  
Cancer Genes ◽  
Biomarker Analysis ◽  
Grade 3

59 Background: Other than the androgen receptor, the TMPRSS2-ERG genomic aberrations in prostate cancer provide the first recent opportunity to target therapy in castration refractory prostate cancer (CRPC). We initiated a phase II clinical trial of cytarabine in docetaxel refractory CRPC on the basis of microarray, in vitro and case report evidence that cytarabine may be particularly effective in men harbouring abnormalities of the ERG oncogenes. Embedded in this clinical trial was the first use of blood mRNA levels of prostate cancer related genes as biomarkers of response and prognosis. Methods: Patients with docetaxel refractory progressive CRPC received intravenous cytarabine at doses between 1g/m2-0.25 g/m2 q3 weekly. Responses were defined according to PCWG2C. 10 patients were enrolled between June 2007 and January 2010. TMPRSS2:ERG, PSA and PCA3 mRNA copies in whole blood collected with PAXgene tubes at the beginning of each cycle and at trial termination were quantified using transcription-mediated amplification assays. The prototype TMPRSS2:ERG assay detects the gene fusion isoform TMPRSS2 exon1 to ERG exon4. Results: No patients demonstrated a serum PSA response (PCWG2C). The average number of cycles administered was 2.6. Significant toxicities including grade 3-4 thrombocytopenia (2) and grade 3-4 neutropenia (3). These toxicities necessitated several dose reductions in the protocol, however most patients were removed from trial for serum PSA progression alone. PCA3 and PSA mRNAs were detectable in 8/10 and 9/10 cases, respectively; there was no correlation between serum PSA and PCA3 or PSA mRNA copy levels in blood. Testing for TMPRSS2:ERG in blood was able to predict the presence or absence of the TMPRSS2-ERG rearrangement in 9/10 cases when compared to 3 colour FISH carried out on baseline biopsies/ prostatectomies (2/10 positive for Exon 4:Exon 1 deletion). Conclusions: Cytarabine administation is ineffective in docetaxel refractory CRPC. Blood mRNA levels of prostate cancer genes reveal novel aspects of prostate cancer biology and have implications for the understanding of circulating tumour cells. [Table: see text]

Clinical outcomes of the combination of bevacizumab and ttfields in patients with recurrent glioblastoma: Results of a phase II clinical trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2537-2537
Author(s):  
Jaleh Fallah ◽  
Rekha T. Chaudhary ◽  
Lisa R. Rogers ◽  
Wei Wei ◽  
Cathy J. Brewer ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Disease Progression ◽  
Muscle Weakness ◽  
Phase Ii ◽  
Day Treatment ◽  
Recurrent Glioblastoma ◽  
Phase Ii Clinical Trial ◽  
Rank Test ◽  
Grade 3 ◽  
Recurrent Gbm

2537 Background: Clinical trials of bevacizumab monotherapy and TTFields monotherapy have shown activity but limited clinical benefit in patients (pts) with recurrent glioblastoma (GBM), with median progression-free survival (PFS) of 2-4 months and median overall survival (OS) of 6-9 months with either treatment modality. In a single-arm phase II clinical trial, the efficacy of the combination of bevacizumab and TTFields in pts with recurrent GBM was investigated. Methods: Pts with histologically confirmed GBM or other grade IV gliomas, who had disease progression after chemoradiation were enrolled in a phase II trial of the combination of bevacizumab and TTFields. Bevacizumab was given at a dose of 10 mg/Kg intravenously every 2 weeks and TTFields was worn by the pts continuously for more than 18 hours per day. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoints were PFS at 6 months and OS at 12 months. Survival outcomes were assessed using the Kaplan-Meier method and compared by log rank test. Treatment-related adverse events were reported according to CTCAE, v4.0 criteria. Results: From April 2013 to December 2017, 25 pts were enrolled and 23 were evaluable: 18 (78%) men and 5 (22%) women, median age 60 years (range 17–78). 21 pts were Caucasian, 1 was African American and 1 of unknown race. After a median follow up of 31.6 months (range: 4.1-59.0 months), 21 out of 23 pts died (4 women and 17 men). The median PFS was 4.1 months (95%CI, 3.6-9.5) and the median OS was 10.5 months (95% CI, 8.2-14.9). The PFS rate at 6 and 12 months were 33% and 19%, respectively. The OS rate at 6 and 12 months were 82% and 46%, respectively. Women had better OS and PFS compared to men, however, the difference was not statistically significant which can be due to the small study population (table). Grade 3 and 4 toxicities considered definitely or probably related to the treatment included hypertension (n = 1) and cerebral infarction (n = 1). Other reported grade 3-4 toxicities (n = 7) included cough, dysphagia, muscle weakness, hyperglycemia, psychosis, seizure, lymphopenia, transaminitis, and muscle weakness considered unlikely to be treatment-related. Conclusions: The combination of bevacizumab and TTFields in is safe and feasible and has clinical efficacy in pts with recurrent GBM. Clinical trial information: NCT01894061 . [Table: see text]

RTID-07. AN INVESTIGATOR-LEAD PHASE II CLINICAL TRIAL OF ACCELERATOR-BASED BNCT FOR REFRACTORY AND RECURRENT HIGH-GRADE MENINGIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi194-vi194
Author(s):  
Shin-Ichi Miyatake ◽  
Shinji Kawabata ◽  
Satoshi Takai ◽  
Masahiko Wanibuchi
Keyword(s):  
Clinical Trial ◽  
Treatment Group ◽  
Supportive Care ◽  
Phase Ii ◽  
Best Supportive Care ◽  
Phase Ii Clinical Trial ◽  
Care Group ◽  
High Grade ◽  
Neutron Sources ◽  
Control Subjects

Abstract BACKGROUD Boron neutron capture therapy (BNCT) is tumor-selective particle radiation. We applied this unique technique and achieved excellent clinical results for recurrent and refractory high-grade meningiomas (HGM) using reactor neutron sources (Neuro-Oncology, in press, doi:10.1093/neuonc/noab108). Recently accelerator-based neutron sources (ABNS) was approved for medical device in Japan for refractory H&N cancers. PURPOSES Based on these situations, we proposed “A phase II clinical trial using accelerator-based BNCT system for refractory recurrent HGM” for AMED in Japan which is similar to NIH in USA. This proposal was successfully accepted. DESIGN We prepared 2 study groups, BNCT test treatment group and control best supportive care group, for RCT. PFS and OS were set-up as primary and secondary endpoints, respectively. Rescue BNCT is allowed for control group patients, if they showed PD during observation. The trial started in August 2019. METHODS Twelve BNCT and 6 control subjects will be included. Patients’ eligibility criteria is recurrent HGM after some radiotherapy. Cyclotron-based ABNS system is used for neutron source. Neutron-irradiation time is determined not to exceed to 7.5 Gy-Eq for scalp dose which was referencing preceding phase I trial for malignant gliomas. PROGRESS As of March 2021, 13 subjects were included, 9 for BNCT treatment group, 4 for control best supportive care group. All 4 control subjects showed PD during 2 months while 8 out of 9 subjects showed SD or PR during observation period and there is a statistical significance in both groups, by Log-rank and Wilcoxon analyses with p=0.0012 and 0.0020, respectively. CONCLUSION We started this RCT and will introduce the interim report of this clinical trial in the meeting. At the SNO meeting we will present further detail of this trial.

scholarly journals SAT-175 Trial in Progress Interim Report: A Phase II Clinical Trial Using Single Agent Cabozantinib in Advanced Adrenocortical Carcinoma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sara Shokry Daniel Bedrose ◽  
Lina Altameemi ◽  
Marilyne Daher ◽  
Gina Tamsen De Rosa ◽  
Jeena Mary Varghese ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Phase Ii ◽  
Adrenocortical Carcinoma ◽  
Hypertensive Crisis ◽  
Response To Therapy ◽  
Phase Ii Clinical Trial ◽  
Study Endpoint ◽  
Close Monitoring ◽  
Grade 3

Abstract BACKGROUND: Adrenocortical carcinoma (ACC) in an aggressive malignancy with suboptimal response to frontline chemotherapy and without established second line treatment. cMET activation is associated with ACC resistance to chemotherapy. Cabozantinib is a multi-kinase inhibitor that targets the VEGFR, c-MET, AXL, and RET receptors. We report interim data about using cabozantinib in ACC through a prospective phase II clinical trial. Methods: This is an investigator-initiated, open label clinical trial to evaluate the efficacy and safety of cabozantinib in patients with unresectable/metastatic ACC (ClinicalTrials.gov Identifier: NCT03370718). The primary objective is 4-month progression-free survival rate (PFS4). Participants are ≥ 18 years old with histologically confirmed ACC. Subjects who used mitotane within 6 months of consent must have mitotane serum level of < 2 mg/L. Cabozantinib starting dose is 60 mg daily with possible dose reductions. Subjects stopped treatment at time of disease progression, death, or occurrence of severe adverse events. Objective tumor responses were assessed per RECIST v.1.1 criteria. Adverse effects were graded per CTCAE v.4.03 Results: At time of data cut off (Oct 28, 2019), we screened 16 patients for enrollment. Ten patients (3 females) received cabozantinib out of whom 5 had history of mitotane use. Nine patients were eligible for response evaluation, defined as having at least one follow up imaging. One patient was taken off study after one week due to hypertensive crisis. Median age at time of diagnosis was 45 years (range 32 - 72). Five patients had hormonally active ACC. Median number of prior lines of systemic therapy was 2 (range 0 -5). Median duration of cabozantinib therapy was 6.6 months (range 0.7 -11.3). Eight patients (80%) were without evidence of progression at 4 months (achieved study endpoint). At time of data cut off, 1 patient had partial response (53% reduction over 8.8 months and ongoing), 3 patients had stable disease, and 5 patients had progressive disease. Nine patients were alive with disease and one patient died (not drug related). Grade 3/4 clinical adverse events included thromboembolic events (3 patients), severe hypertension (1 patient), intracranial hemorrhage secondary to hypertensive crisis (1 patient), weight loss (1 patient), and abdominal pain (1 patient). Grade 3/4 laboratory adverse events included increased AST (2 patient), increased ALT (1 patient), increased GGT, increased amylase (1 patient), increased lipase (1 patient) and hyponatremia (1 patient). Conclusions: In this interim analysis of phase II study, majority of subjects reached the study primary endpoint (PFS4). These data are in favor of continuing study accrual to assess magnitude of response to therapy and safety profile in ACC. Aggressive blood pressure management and close monitoring of liver enzymes are crucial to ensure the safety of study subjects.

Alpha-type-1 Polarized Dendritic Cell-based Vaccination in Newly Diagnosed High-grade Glioma: A Phase II Clinical Trial

2020 ◽  
Vol 40 (11) ◽  
pp. 6473-6484
Author(s):  
KOICHI MITSUYA ◽  
YASUTO AKIYAMA ◽  
AKIRA IIZUKA ◽  
HARUO MIYATA ◽  
SHOICHI DEGUCHI ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Dendritic Cell ◽  
Phase Ii ◽  
High Grade Glioma ◽  
Phase Ii Clinical Trial ◽  
High Grade ◽  
Newly Diagnosed ◽  
Alpha Type

Priming immunotherapy with radiotherapy (RT) in advanced non-small cell lung cancer (NSCLC) and head and neck squamous cell cancer (HNSCC): Interim analysis of phase II clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2628-2628
Author(s):  
Aasems Jacob ◽  
Alexander Kreimer ◽  
Jing Wei ◽  
Jianrong Wu ◽  
Lauren Corum ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Phase Ii ◽  
Interim Analysis ◽  
Cell Cancer ◽  
Phase Ii Clinical Trial ◽  
Cell Phenotype ◽  
Second Line ◽  
Combination Methods ◽  
Grade 3

2628 Background: Preclinical models demonstrate that combined RT with immune checkpoint inhibitor (ICI) results in specific CD8+ T-cell phenotype associated with a tumor-reactive population resulting in significant tumor response. Sequential treatment could allow radiation to release tumor antigens from immune inaccessible areas and provide robust anti-tumor immune response with ICI. We report an interim analysis of the phase II clinical trial evaluating the efficacy and safety of the combination. Methods: Advanced NSCLC and HNSCC patients who had initiated on FDA approved single-agent ICI were eligible. Patients were given SBRT (BED>100Gy) or 30 Gy fractionated RT delivered as a 3-dimensional dose to a single metastatic site within 14 days of the first ICI dose. Primary objective was 6-month PFS and secondary objectives were safety and tolerability, 1Y PFS and OS. This interim analysis was done after enrollment of 43 patients. Results: Between 10/2017 to 1/2021, 43 patients were enrolled, and 38 included in this analysis. Median age was 62 years; 26 patients were male. 9 patients received ICI for NSCLC as first-line, 7 for NSCLC second-line and 22 for HNSCC second-line. 24 patients received pembrolizumab and 14 nivolumab; 21 had SBRT and 17 fractionated RT. Median follow up duration was 11.8m (range: 2.7 - 31.4m) for patients without progressive disease (PD). 10 patients were off-study, 7 continuing treatment. 15 died and 26 had PD. 14 patients died of malignancy and cause of death for one patient was unknown. 6-month PFS was 49.19% with median PFS of 5.5 months. (table) Fifty-two grade-3-5 adverse events (AEs) were reported among 21 subjects. Most common were transaminitis (n=15), lymphopenia (n=8), and GI side effects (n=4). Treatment related AEs included 19 grade-3 events, and none were grade 4/5. Two grade-5 AEs were from PD (oral bleeding and unspecified). There were 20 grade-1/2 and 3 grade-3 immune related adverse events (IRAEs). No grade-4/5 IRAEs were reported. Two patients discontinued treatment due to grade 3 transaminitis. Conclusions: Interim analysis shows that 6m PFS was acceptable with majority of patients being second-line metastatic HNSCC who historically had mPFS of 2.1-2.3 months and mOS 7.7-8.4 months in Checkmate-141/KEYNOTE-040 trials. Hence, the combination is of further interest and accrual will continue to reach the goal. The combination therapy was tolerable without unexpected AEs. Majority of deaths were from disease progression. No treatment related grade 4/5 adverse events were reported. Two patients discontinued treatment due to grade-3 IRAE. Clinical trial information: NCT03313804. [Table: see text]

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