scholarly journals Intravital Microscopy (IVM) in Human Solid Tumors: Novel Protocol to Examine Tumor-Associated Vessels (Preprint)

2019 ◽  
Author(s):  
Denslow Allerton Trumbull ◽  
Riccardo Lemini ◽  
Sanjay P Bagaria ◽  
Enrique F Elli ◽  
Dorin T Colibaseanu ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Surgical Resection ◽  
Intravital Microscopy ◽  
Research Team ◽  
Patient Treatment ◽  
Direct Visualization ◽  
Open Label ◽  
Systemic Treatments ◽  
Human Solid Tumors ◽  
Improve Patient

BACKGROUND Intravital microscopy (IVM) allows the real-time, direct visualization of microscopic blood vessels. This pilot clinical trial will elucidate the physical and functional characteristics of vessels associated with solid tumors. OBJECTIVE The main objective of this study is to determine the feasibility of performing IVM in patients with solid tumors during the standard course of surgical resection. IVM will also be performed when vasopressors or fluid boluses are administered during the standard course of the operation. METHODS This is an open-label, nonrandomized, single-center, pilot study of IVM observation in subjects with solid tumors undergoing surgical resection. RESULTS This study was active on January 1, 2019 (NCT03823144) and funded by the Mayo Clinic Florida Cancer Focused Research Team Award. As of September 27, 2020, we had enrolled 20 patients. Accrual period is expected to end by December 31, 2021. CONCLUSIONS This trial will support the development of interventions to improve patient treatment by extending the application of IVM to the tumor microenvironment. IVM observations during volume and pressor management at the time of surgery may aid in the development of strategies to augment responses to systemic treatments. INTERNATIONAL REGISTERED REPORT PRR1-10.2196/15677

scholarly journals Intravital Microscopy (IVM) in Human Solid Tumors: Novel Protocol to Examine Tumor-Associated Vessels

10.2196/15677 ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. e15677
Author(s):  
Denslow Allerton Trumbull ◽  
Riccardo Lemini ◽  
Sanjay P Bagaria ◽  
Enrique F Elli ◽  
Dorin T Colibaseanu ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Surgical Resection ◽  
Intravital Microscopy ◽  
Research Team ◽  
Patient Treatment ◽  
Direct Visualization ◽  
Open Label ◽  
Systemic Treatments ◽  
Human Solid Tumors ◽  
Improve Patient

Background Intravital microscopy (IVM) allows the real-time, direct visualization of microscopic blood vessels. This pilot clinical trial will elucidate the physical and functional characteristics of vessels associated with solid tumors. Objective The main objective of this study is to determine the feasibility of performing IVM in patients with solid tumors during the standard course of surgical resection. IVM will also be performed when vasopressors or fluid boluses are administered during the standard course of the operation. Methods This is an open-label, nonrandomized, single-center, pilot study of IVM observation in subjects with solid tumors undergoing surgical resection. Results This study was active on January 1, 2019 (NCT03823144) and funded by the Mayo Clinic Florida Cancer Focused Research Team Award. As of September 27, 2020, we had enrolled 20 patients. Accrual period is expected to end by December 31, 2021. Conclusions This trial will support the development of interventions to improve patient treatment by extending the application of IVM to the tumor microenvironment. IVM observations during volume and pressor management at the time of surgery may aid in the development of strategies to augment responses to systemic treatments. International Registered Report Identifier (IRRID) PRR1-10.2196/15677

Genomic Medicine Frontier in Human Solid Tumors: Prospects and Challenges

2013 ◽  
Vol 31 (15) ◽  
pp. 1874-1884 ◽  
Author(s):  
Rodrigo Dienstmann ◽  
Jordi Rodon ◽  
Jordi Barretina ◽  
Josep Tabernero
Keyword(s):  
Solid Tumors ◽  
Cancer Progression ◽  
Cancer Genomics ◽  
Genomic Medicine ◽  
Genomic Data ◽  
Cost Effective ◽  
Assessment Model ◽  
Historical View ◽  
Systemic Treatments ◽  
Human Solid Tumors

Recent discoveries of genomic alterations that underlie and promote the malignant phenotype, together with an expanded repertoire of targeted agents, have provided many opportunities to conduct hypothesis-driven clinical trials. The ability to profile each unique cancer for actionable aberrations by using high-throughput technologies in a cost-effective way provides unprecedented opportunities for using matched therapies in a selected patient population. The major challenges are to integrate and make biologic sense of the substantial genomic data derived from multiple platforms. We define two different approaches for the analysis, interpretation, and clinical applicability of genomic data: (1) the genomically stratified model originates from the “one test-one drug” paradigm and is currently being expanded with an upfront multicategorical approach following recent advances in multiplexed genotyping platforms; and (2) the comprehensive assessment model is based on whole-genome, -exome, and -transcriptome data and allows identification of novel drivers and subsequent therapies in the experimental setting. Tumor heterogeneity and evolution of the diverse populations of cancer cells during cancer progression, influenced by the effects of systemic treatments, will need to be addressed in the new scenario of early drug development. Logistical issues related to prescreening strategies and trial allocation, in addition to concerns in the economic and ethical domains, must be taken into consideration. Here we present a historical view of how increased understanding of cancer genomics has been translated to the clinic and discuss the prospects and challenges for further implementation of a personalized treatment strategy for human solid tumors.

scholarly journals A first-in-human, phase 1 study of the NEDD8 activating enzyme E1 inhibitor TAS4464 in patients with advanced solid tumors

2021 ◽  
Author(s):  
Noboru Yamamoto ◽  
Toshio Shimizu ◽  
Kan Yonemori ◽  
Shigehisa Kitano ◽  
Shunsuke Kondo ◽  
...  
Keyword(s):  
Liver Function ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Enzyme Inhibitor ◽  
Phase 1 ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Open Label ◽  
Phase 1 Study ◽  
Open Label Phase

SummaryBackground This open-label, phase 1 study investigated TAS4464, a potent NEDD8-activating enzyme inhibitor, in patients with advanced/metastatic solid tumors (JapicCTI-173,488; registered 13/01/2017). The primary objective was dose-limiting toxicities (DLTs). Maximum-tolerated dose (MTD) was investigated using an accelerated titration design. Methods The starting 10-mg/m2 dose was followed by an initial accelerated stage (weekly dosing; n = 11). Based on liver function test (LFT) results, a 14-day, 20-mg/m2 dose lead-in period was implemented (weekly dosing with lead-in; n = 6). Results Abnormal LFT changes and gastrointestinal effects were the most common treatment-related adverse events (AEs). DLTs with 56-mg/m2 weekly dosing occurred in 1/5 patients; five patients had grade ≥ 2 abnormal LFT changes at 40- and 56-mg/m2 weekly doses. Further dose escalation ceased because of the possibility of severe abnormal LFT changes occurring. DLTs with weekly dosing with lead-in occurred in 1/5 patients at a 56-mg/m2 dose; MTD could not be determined because discontinuation criteria for additional enrollment at that particular dose level were met. As no further enrollment at lower doses occurred, dose escalation assessment was discontinued. Serious treatment-related AEs, AEs leading to treatment discontinuation, and DLTs were all related to abnormal LFT changes, suggesting that TAS4464 administration could affect liver function. This effect was dose-dependent but considered reversible. Complete or partial responses to TAS4464 were not observed; one patient achieved prolonged stable disease. Conclusions MTD could not be determined due to TAS4464 effects on liver function. Further evaluation of the mechanism of NEDD8-activating enzyme inhibitor-induced abnormal liver function is required. Trial registration number JapicCTI-173,488 (registered with Japan Pharmaceutical Information Center). Registration date 13 January 2017

scholarly journals A phase 1, open-label, drug–drug interaction study of rucaparib with rosuvastatin and oral contraceptives in patients with advanced solid tumors

2021 ◽  
Author(s):  
Mingxiang Liao ◽  
Krzysztof G. Jeziorski ◽  
Monika Tomaszewska-Kiecana ◽  
István Láng ◽  
Marek Jasiówka ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Solid Tumors ◽  
Oral Contraceptives ◽  
Interaction Analysis ◽  
Phase 1 ◽  
Geometric Mean ◽  
Pharmacokinetic Analysis ◽  
Advanced Solid Tumors ◽  
Open Label ◽  
Drug Drug Interaction

Abstract Purpose This study aimed at evaluating the effect of rucaparib on the pharmacokinetics of rosuvastatin and oral contraceptives in patients with advanced solid tumors and the safety of rucaparib with and without coadministration of rosuvastatin or oral contraceptives. Methods Patients received single doses of oral rosuvastatin 20 mg (Arm A) or oral contraceptives ethinylestradiol 30 µg + levonorgestrel 150 µg (Arm B) on days 1 and 19 and continuous doses of rucaparib 600 mg BID from day 5 to 23. Serial blood samples were collected with and without rucaparib for pharmacokinetic analysis. Results Thirty-six patients (n = 18 each arm) were enrolled and received at least 1 dose of study drug. In the drug–drug interaction analysis (n = 15 each arm), the geometric mean ratio (GMR) of maximum concentration (Cmax) with and without rucaparib was 1.29 for rosuvastatin, 1.09 for ethinylestradiol, and 1.19 for levonorgestrel. GMR of area under the concentration–time curve from time zero to last quantifiable measurement (AUC0–last) was 1.34 for rosuvastatin, 1.43 for ethinylestradiol, and 1.56 for levonorgestrel. There was no increase in frequency of treatment-emergent adverse events (TEAEs) when rucaparib was given with either of the probe drugs. In both arms, most TEAEs were mild in severity and considered unrelated to study treatment. Conclusion Rucaparib 600 mg BID weakly increased the plasma exposure to rosuvastatin or oral contraceptives. Rucaparib safety profile when coadministered with rosuvastatin or oral contraceptives was consistent with that of rucaparib monotherapy. Dose adjustments of rosuvastatin and oral contraceptives are not necessary when coadministered with rucaparib. ClinicalTrials.gov NCT03954366; Date of registration May 17, 2019.

scholarly journals Selinexor in combination with topotecan in patients with advanced or metastatic solid tumors: Results of an open-label, single-center, multi‐arm phase Ib study

2021 ◽  
Author(s):  
Kyaw Zin Thein ◽  
Sarina A. Piha-Paul ◽  
Apostolia Tsimberidou ◽  
Daniel D. Karp ◽  
Filip Janku ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Single Center ◽  
Open Label ◽  
Phase Ib

scholarly journals Large hypomethylated blocks as a universal defining epigenetic alteration in human solid tumors

2014 ◽  
Vol 6 (8) ◽  
Author(s):  
Winston Timp ◽  
Hector Corrada Bravo ◽  
Oliver G McDonald ◽  
Michael Goggins ◽  
Chris Umbricht ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Epigenetic Alteration ◽  
Human Solid Tumors
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