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Phase I trials

I Schütz-Fuhrmann, J Castañeda, Y Reznik, R Aronson, I Conget, S Liabat, S Runzis, S de Portu, O Cohen
The recent OpT2mise randomized trial compared the efficacy of insulin pump therapy and multiple daily injections (MDI) in people with Type 2 diabetes and HbA1c levels that remained ≥64 mmol/mol (8.0%) despite insulin dose optimization [1,2]. During the initial 6-month randomized phase of the study, pump therapy was shown to produce a significant improvement in glycaemic control and a 20% reduction in total daily insulin dose, compared with MDI therapy [1], and these benefits were sustained during the subsequent 6-month extension phase during which all participants received pump therapy [2]...
October 22, 2016: Diabetic Medicine: a Journal of the British Diabetic Association
Britton Trabert, Ronald C Eldridge, Ruth M Pfeiffer, Meredith S Shiels, Troy J Kemp, Chantal Guillemette, Patricia Hartge, Mark E Sherman, Louise A Brinton, Amanda Black, Anil K Chaturvedi, Allan Hildesheim, Sonja I Berndt, Mahboobeh Safaeian, Ligia Pinto, Nicolas Wentzensen
Inflammation is proposed to increase risk of developing endometrial cancer, but few prospective epidemiologic studies have investigated the relationship between circulating inflammation markers and endometrial cancer risk. In a nested case-control study within the PLCO Screening Trial we measured serum levels of 64 inflammation-related biomarkers in 284 incident endometrial cancer cases and 284 matched controls. Using multivariable logistic regression inflammation markers were evaluated individually and combined into a cross-validated inflammation score...
October 22, 2016: International Journal of Cancer. Journal International du Cancer
F Casas, I Henríquez, A Bejar, X Maldonado, A Alvarez, C González-Sansegundo, A Boladeras, F Ferrer, A Hervás, I Herruzo, M Caro, I Rodriguez, C Ferrer
PURPOSE: We compared biochemical control and quality of life with intermittent (6 months) versus continuous (36 months) androgen deprivation therapy (ADT) in a non-inferiority randomized phase 3 trial in patients with biochemical failure (BF) after external beam radical radiotherapy (EBRT). MATERIALS AND METHODS: Patients were stratified according to the Gleason score (GS) and were classified as low risk with a GS < 6 and 7 (3 + 4) and high risk with a GS of 7 (4 + 3) and >7...
October 21, 2016: Clinical & Translational Oncology
Ana M Denis-Bacelar, Sarah J Chittenden, David P Dearnaley, Antigoni Divoli, Joe M O'Sullivan, V Ralph McCready, Bernadette Johnson, Yong Du, Glenn D Flux
PURPOSE: To investigate the role of patient-specific dosimetry as a predictive marker of survival and as a potential tool for individualised molecular radiotherapy treatment planning of bone metastases from castration-resistant prostate cancer, and to assess whether higher administered levels of activity are associated with a survival benefit. METHODS: Clinical data from 57 patients who received 2.5-5.1 GBq of (186)Re-HEDP as part of NIH-funded phase I/II clinical trials were analysed...
October 21, 2016: European Journal of Nuclear Medicine and Molecular Imaging
Matthew D Hale, Matthew Nankivell, Gordon G Hutchins, Sally P Stenning, Ruth E Langley, Wolfram Mueller, Nicholas P West, Alexander I Wright, Darren Treanor, Lindsay C Hewitt, William H Allum, David Cunningham, Jeremy D Hayden, Heike I Grabsch
BACKGROUND: Neoadjuvant chemotherapy followed by surgery is the standard of care for UK patients with locally advanced resectable oesophageal carcinoma (OeC). However, not all patients benefit from multimodal treatment and there is a clinical need for biomarkers which can identify chemotherapy responders. This study investigated whether the proportion of tumour cells per tumour area (PoT) measured in the pre-treatment biopsy predicts chemotherapy benefit for OeC patients. PATIENTS AND METHODS: PoT was quantified using digitized haematoxylin/eosin stained pre-treatment biopsy slides from 281 OeC patients from the UK MRC OE02 trial (141 treated by surgery alone (S); 140 treated by 5-fluorouracil/cisplatin followed by surgery (CS))...
October 18, 2016: Oncotarget
Klaus Kratochwill, Michael Boehm, Rebecca Herzog, Katharina Gruber, Anton Michael Lichtenauer, Lilian Kuster, Dagmar Csaicsich, Andreas Gleiss, Seth L Alper, Christoph Aufricht, Andreas Vychytil
BACKGROUND: Peritonitis and ultrafiltration failure remain serious complications of chronic peritoneal dialysis (PD). Dysfunctional cellular stress responses aggravate peritoneal injury associated with PD fluid exposure, potentially due to peritoneal glutamine depletion. In this randomized cross-over phase I/II trial we investigated cytoprotective effects of alanyl-glutamine (AlaGln) addition to glucose-based PDF. METHODS: In a prospective randomized cross-over design, 20 stable PD outpatients underwent paired peritoneal equilibration tests 4 weeks apart, using conventional acidic, single chamber 3...
2016: PloS One
K Reich, M Gooderham, L Green, A Bewley, Z Zhang, I Khanskaya, R M Day, J Goncalves, K Shah, V Piguet, J Soung
BACKGROUND: Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, has demonstrated efficacy in patients with moderate to severe psoriasis. OBJECTIVE: Evaluate efficacy and safety of apremilast vs. placebo in biologic-naive patients with moderate to severe plaque psoriasis and safety of switching from etanercept to apremilast in a phase IIIb, randomized, double-blind, placebo-controlled study (NCT01690299). METHODS: 250 patients were randomized to placebo (n=84), apremilast 30 mg BID (n=83) or etanercept 50 mg QW (n=83) through Week 16; thereafter, all patients continued or switched to apremilast through Week 104...
October 21, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Gianluigi Franci, Federica Sarno, Angela Nebbioso, Lucia Altucci
Epigenetic modifications are functionally involved in gene expression regulation. In particular, histone posttranslational modifications play a crucial role in functional chromatin organization. Several drugs able to inhibit or stimulate some families of proteins involved in epigenetic histone regulation have been found, a number of which are FDA-approved for the treatment of cutaneous T-cell lymphoma or are in phase I/II/III clinical trials for solid tumors. Although some protein families, such as histone deacetylases and their inhibitors, are well characterized, our understanding of histone lysine demethylases is still incomplete...
October 21, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Andrew Kl Goey, Tristan M Sissung, Cody J Peer, William D Figg
The histone deacetylase inhibitor valproic acid (VPA) has been used for many decades in neurology and psychiatry. The more recent introduction of the histone deacetylase inhibitors (HDIs) belinostat, romidepsin and vorinostat for treatment of hematological malignancies indicates the increasing popularity of these agents. Belinostat, romidepsin and vorinostat are metabolized or transported by polymorphic enzymes or drug transporters. Thus, genotype-directed dosing could improve pharmacotherapy by reducing the risk of toxicities or preventing suboptimal treatment...
October 21, 2016: Pharmacogenomics
H H Yoon, J C Bendell, F S Braiteh, I Firdaus, P A Philip, A L Cohn, N Lewis, D M Anderson, E Arrowsmith, J D Schwartz, L Gao, Y Hsu, Y Xu, D Ferry, S R Alberts, Z A Wainberg
BACKGROUND: We report the first randomized, Phase II trial of ramucirumab, an anti-vascular endothelial growth factor receptor-2 monoclonal antibody, as front-line therapy in patients with advanced adenocarcinoma of the esophagus or gastric/gastroesophageal junction (GEJ). PATIENTS AND METHODS: Patients from the USA with advanced esophageal, gastric, or GEJ adenocarcinoma randomly received (1:1) mFOLFOX6 plus ramucirumab (8 mg/kg) or mFOLFOX6 plus placebo every 2 weeks...
October 20, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Paul Monsarrat, Philippe Kemoun, Jean-Noel Vergnes, Luc Sensebe, Louis Casteilla, Valerie Planat-Benard
BACKGROUND AIMS: Using innovative tools derived from social network analysis, the aims of this study were (i) to decipher the spatial and temporal structure of the research centers network dedicated to the therapeutic uses of mesenchymal stromal cells (MSCs) and (ii) to measure the influence of fields of applications, cellular sources and industry funding on network topography. METHODS: From each trial using MSCs reported on, all research centers were extracted...
October 17, 2016: Cytotherapy
Paul J Karanicolas, Yulia Lin, Jordan Tarshis, Calvin H L Law, Natalie G Coburn, Julie Hallet, Barto Nascimento, Janusz Pawliszyn, Stuart A McCluskey
BACKGROUND: Hyperfibrinolysis may occur due to systemic inflammation or hepatic injury that occurs during liver resection. Tranexamic acid (TXA) is an antifibrinolytic agent that decreases bleeding in various settings, but has not been well studied in patients undergoing liver resection. METHODS: In this prospective, phase II trial, 18 patients undergoing major liver resection were sequentially assigned to one of three cohorts: (i) Control (no TXA); (ii) TXA Dose I - 1 g bolus followed by 1 g infusion over 8 h; (iii) TXA Dose II - 1 g bolus followed by 10 mg/kg/hr until the end of surgery...
October 17, 2016: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
Matthew I Milowsky, Matthew D Galsky, Michael J Morris, Daniel J Crona, Daniel J George, Robert Dreicer, Kin Tse, Jesika Petruck, Iain J Webb, Neil H Bander, David M Nanus, Howard I Scher
BACKGROUND: This phase 1/2 study evaluated the dose-limiting toxicity and maximum tolerated dose of MLN2704, a humanized monoclonal antibody MLN591 targeting prostate-specific membrane antigen, linked to the maytansinoid DM1 in patients with progressive metastatic castration-resistant prostate cancer. PATIENTS AND METHODS: A total of 62 patients received MLN2704 at ascending doses on 4 schedules: weekly (60, 84, 118, and 165mg/m(2); 12 patients); every 2 weeks (120, 168, 236, and 330mg/m(2); 15 patients); every 3 weeks (330 and 426mg/m(2); 18 patients); and on days 1 and 15 of a 6-week schedule (6-week cycle, 330mg/m(2); 17 patients)...
October 17, 2016: Urologic Oncology
Si Yeol Song, Kyu-Pyo Kim, Seong-Yun Jeong, Jin Park, Jaesook Park, Joohee Jung, Hye Kyung Chung, Sa-Won Lee, Min Hyo Seo, Jung-Shin Lee, Kyung Hae Jung, Eun Kyung Choi
We assessed the efficacy of the polymeric nanoparticle containing docetaxel (PNP-DTX) in preclinical mouse models and determined the maximum tolerated dose (MTD) through clinical study. Subcutaneous and orthotopic mouse models were dedicated. Tumor growth delay in orthotopic model and quantification of in vivo imaging in orthotopic model were evaluated. Phase I clinical study was a single-center, prospective, open-label trial in advanced solid tumors. PNP-DTX was injected intravenously and the starting dose was 20 mg/m2 escalated to 35 mg/m2, 45 mg/m2, 60 mg/m2 and 75 mg/m2...
October 14, 2016: Oncotarget
Carsten-O Sahlmann, Kia Homayounfar, Martin Niessner, Jerzy Dyczkowski, Lena-Christin Conradi, Friederike Braulke, Birgit Meller, Tim Beißbarth, B Michael Ghadimi, Johannes Meller, David M Goldenberg, Torsten Liersch
BACKGROUND: In previous work, a single administration of anticarcinoembryonic antigen (anti-CEA) (131) I-labetuzumab radioimmunotherapy (RIT) after complete resection of colorectal liver metastases was well tolerated and significantly improved survival compared with controls. In the current phase 2 trial, the authors studied repeated RIT in the same setting, examining safety, feasibility, and efficacy. METHODS: Sixty-three patients (median age, 64.5 years) received RIT at 40 to 50 millicuries/m(2) per dose...
October 20, 2016: Cancer
Vincent Ronfard, Alain Vertes, Michael May, Anne Dupraz, Mark van Dyke, Yves Bayon
"Evaluating the Past & Present of Regenerative Medicine (RM)" was the first part of an Industry Symposium dedicated to the subject during the 2015 World TERMIS Congress in Boston. This working session presented a critical review of the current RM landscape in Europe and North America with possible projections for the future. Interestingly, the RM development cycle seems to obey the Gartner hype cycle, now at the enlightenment phase, after past exaggerated expectations and discouragements, as suggested by increasing numbers of clinical trials and recent market approvals of RM solutions in both Europe (Glybera & Holoclar® from Chiesi Pharma and Strimvelis® from GSK) and Japan (Remestemcel-L from Mesoblast® )...
October 20, 2016: Tissue Engineering. Part B, Reviews
F Creamer, A Balfour, S Nimmo, I Foo, J D Norrie, L J Williams, K C Fearon, H M Paterson
BACKGROUND: Combined oral modified-release oxycodone-naloxone may reduce opioid-induced postoperative gut dysfunction. This study examined the feasibility of a randomized trial of oxycodone-naloxone within the context of enhanced recovery for laparoscopic colorectal resection. METHODS: In a single-centre open-label phase II feasibility study, patients received analgesia based on either oxycodone-naloxone or oxycodone. Primary endpoints were recruitment, retention and protocol compliance...
October 20, 2016: British Journal of Surgery
Wataru Obara, Takashi Karashima, Kazuyoshi Takeda, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata, Keiji Inoue, Toyomasa Katagiri, Taro Shuin, Yusuke Nakamura, Tomoaki Fujioka
PURPOSE: Through genome-wide expression profile analysis, hypoxia-inducible protein 2 (HIG2) has previously been identified as an oncoprotein involved in development/progression of renal cell carcinoma (RCC). We subsequently identified a highly immunogenic HLA-A*0201/0206-restricted epitope peptide (HIG2-9-4) corresponding to a part of HIG2 and applied it as a therapeutic vaccine. We conducted a phase I clinical trial using the HIG2-9-4 peptide for patients with advanced RCC. MATERIALS AND METHODS: Nine patients having HLA-A*0201 or HLA-A*0206 with metastatic or unresectable RCC after failure of the cytokine and/or tyrosine kinase inhibitor therapies were enrolled in this study...
October 18, 2016: Cancer Immunology, Immunotherapy: CII
Andrej M Kielbassa, Georg Glockner, Michael Wolgin, Karl Glockner
BACKGROUND: With the Minamata Convention the use of mercury will be phased down, and this undoubtedly will have an effect on dental treatment regimens and economic resources. Composite resin restorations are considered viable alternatives to amalgam fillings; however, these will not be covered completely by health insurance systems in many countries. Recently, a high-viscosity glass-ionomer cement (hvGIC) processed with a resinous coating (RC) has been introduced, and has been marketed as a restorative material in load-bearing Class I cavities (and in Class II cavities with limited size), thus serving as a possible alternative to amalgam fillings...
2016: Quintessence International
Troels Holz Borch, Lotte Engell-Noerregaard, Trine Zeeberg Iversen, Eva Ellebaek, Özcan Met, Morten Hansen, Mads Hald Andersen, Per Thor Straten, Inge Marie Svane
INTRODUCTION: Vaccination with dendritic cells (DCs) has generally not fulfilled its promise in cancer immunotherapy due to ineffective translation of immune responses into clinical responses. A proposed reason for this is intrinsic immune regulatory mechanisms, such as regulatory T cells (Tregs). A metronomic regimen of cyclophosphamide (mCy) has been shown to selectively deplete Tregs. To test this in a clinical setting, we conducted a phase I trial to evaluate the feasibility and safety of vaccination with DCs transfected with mRNA in combination with mCy in patients with metastatic malignant melanoma (MM)...
2016: Oncoimmunology
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