Read by QxMD icon Read

Phase I trials

Reshma Jagsi, Kent A Griffith, Jennifer R Bellon, Wendy A Woodward, Janet K Horton, Alice Ho, Felix Y Feng, Corey Speers, Beth Overmoyer, Michael Sabel, Anne F Schott, Lori Pierce
Purpose Locoregional control for inflammatory breast cancers and chest wall recurrences is suboptimal, which has motivated interest in radiosensitization to intensify therapy. Preclinical studies have suggested a favorable therapeutic index when poly (ADP-ribose) polymerase inhibitors are used as radiosensitizers; clinical investigation is necessary to establish appropriate dosing and confirm safety. Patients and Methods We conducted a multi-institutional phase I study of veliparib and concurrent radiotherapy (RT) to the chest wall and regional lymph nodes in 30 patients with inflammatory or locally recurrent breast cancer after complete surgical resection...
March 20, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Marlene Seegräber, Jerome Srour, Alexandra Walter, Macarena Knop, Andreas Wollenberg
Dupilumab is a new treatment option for patients with moderate-to-severe atopic dermatitis. It blocks IL-4/IL13-signaling and thereby inhibits receptor signaling downstream the JAK-STAT-pathway. Three of the main disease mechanisms of atopic dermatitis are affected by blocking this pathway; the decrease of skin barrier function, the class switch to IgE and the TH2-differentiation. Areas Covered: Dupilumab showed promising results in clinical trials of phase I-III. Clinical outcome parameters such as SCORAD, EASI, IGA and BSA improved with dupilumab...
March 20, 2018: Expert Review of Clinical Pharmacology
Tim L Wigal, Jeffrey H Newcorn, Nelson Handal, Sharon B Wigal, Ioulietta Mulligan, Virginia Schmith, Eric Konofal
BACKGROUND: Mazindol is under investigation for the treatment of attention-deficit/hyperactivity disorder (ADHD) because of its alertness-enhancing properties. A novel controlled-release (CR) formulation of mazindol was developed to allow once-daily dosing. OBJECTIVE: The aim of this study was to evaluate the efficacy of mazindol CR in adults with ADHD. DESIGN: We conducted a randomized, double-blind, placebo-controlled 6-week trial. METHODS: Subjects diagnosed with ADHD using the Mini-International Neuropsychiatric Structured Interview (MINI) and with an ADHD Rating Scale, Diagnostic and Statistical Manual of Mental Disorders 5th Edition (ADHD-RS-DSM5) score ≥ 28 were randomized to receive placebo or 1-3 mg/day of mazindol for 6 weeks...
March 19, 2018: CNS Drugs
Hironori Nakagami, Ryuichi Morishita
PURPOSE OF REVIEW: Vaccines are commonly used as preventive methods, primarily against infectious diseases. The goal of our study is to develop the therapeutic vaccine for hypertension. RECENT FINDINGS: We and others recently reported that an angiotensin II (AngII) vaccine for hypertension successfully attenuated elevated blood pressures in an animal model without any immunogenic side effects. In this system, an immunogenic molecule (i.e., KLH) with adjuvants provides an antigen that supports the activation of helper T cells...
March 19, 2018: Current Hypertension Reports
Hidehiro Tajima, Mitsuyoshi Okazaki, Takahisa Yamaguchi, Yoshinao Ohbatake, Koichi Okamoto, Shinichi Nakanuma, Shiro Terai, Seisho Sakai, Jun Kinoshita, Isamu Makino, Keishi Nakamura, Hironori Hayashi, Katsunobu Oyama, Masafumi Inokuchi, Tomoharu Miyashita, Hiroyuki Takamura, Itasu Ninomiya, Sachio Fushida, Tetsuo Ohta
The prognosis of patients with unresectable or recurrent pancreatic cancers is very poor. Prior to development of nab-paclitaxel (PTX) plus gemcitabine (GEM) therapy and FOLFIRINOX therapy, there was no recommended third-line chemotherapy after 5-fluorouracil (5-FU) and GEM-based regimens. The present study conducted a Phase I clinical trial of weekly low-dose PTX as a third-line palliative chemotherapy for patients with pancreatic cancer. PTX was administered on days 1, 8, 15, and 22 of each cycle, repeated twice as follows: Level 1, 40 mg/m2 (n=6); Level 2, 50 mg/m2 (n=4)...
April 2018: Molecular and Clinical Oncology
Nicolas Noël, Béatrice Jacquelin, Nicolas Huot, Cécile Goujard, Olivier Lambotte, Michaela Müller-Trutwin
Human immunodeficiency virus (HIV) induces a persistent and incurable infection. However, the combined antiretroviral treatment (cART) has markedly changed the evolution of the infection and transformed a deadly disease into a manageable chronic infection. Withdrawal of cART generally leads though to resumption of the viral replication. The eradication of the virus from its cellular and anatomical reservoirs remains a goal-to-achieve for a cure. In this context, developing novel therapies contributing to this aim are an important field of research...
March 9, 2018: Cytokine & Growth Factor Reviews
Paula Ortiz-Romero, Cristina Borralleras, Mònica Bosch-Morató, Biuse Guivernau, Guillermo Albericio, Francisco J Muñoz, Luis A Pérez-Jurado, Victoria Campuzano
Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a heterozygous deletion of 26-28 genes at chromosome band 7q11.23. The complete deletion (CD) mouse model mimics the most common deletion found in WBS patients and recapitulates most neurologic features of the disorder along with some cardiovascular manifestations leading to significant cardiac hypertrophy with increased cardiomyocytes' size. Epigallocatechin-3-gallate (EGCG), the most abundant catechin found in green tea, has been associated with potential health benefits, both on cognition and cardiovascular phenotypes, through several mechanisms...
2018: PloS One
V Damarla, D Dobrosotskaya, F Siddiqui, I Wollner, M Raoufi, J Li, D Kwon, G Khan
No abstract text is available yet for this article.
March 2018: European Journal of Cancer
Henrieta Fraser, Niloufar Safinia, Nathali Grageda, Sarah Thirkell, Katie Lowe, Laura J Fry, Cristiano Scottá, Andrew Hope, Christopher Fisher, Rachel Hilton, David Game, Paul Harden, Andrew Bushell, Kathryn Wood, Robert I Lechler, Giovanna Lombardi
The concept of regulatory T cell (Treg)-based immunotherapy has enormous potential for facilitating tolerance in autoimmunity and transplantation. Clinical translation of Treg cell therapy requires production processes that satisfy the rigors of Good Manufacturing Practice (GMP) standards. In this regard, we report our findings on the implementation of a robust GMP compliant process for the ex vivo expansion of clinical grade Tregs, demonstrating the feasibility of this developed process for the manufacture of a final product for clinical application...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
Jessica Da Gama Duarte, Sagun Parakh, Miles C Andrews, Katherine Woods, Anupama Pasam, Candani Tutuka, Simone Ostrouska, Jonathan M Blackburn, Andreas Behren, Jonathan Cebon
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma. The first ICI to demonstrate clinical benefit, ipilimumab, targets cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4); however, the long-term overall survival is just 22%. More than 40 years ago intralesional (IL) bacillus Calmette-Guérin (BCG), a living attenuated strain of Mycobacterium bovis , was found to induce tumor regression by stimulating cell-mediated immunity following a localized and self-limiting infection...
2018: Frontiers in Immunology
Michael L Maitland, Sarina Piha-Paul, Gerald Falchook, Razelle Kurzrock, Ly Nguyen, Linda Janisch, Sanja Karovic, Mark McKee, Elizabeth Hoening, Shekman Wong, Wijith Munasinghe, Joann Palma, Cherrie Donawho, Guinan K Lian, Peter Ansell, Mark J Ratain, David Hong
BACKGROUND: Ilorasertib (ABT-348) inhibits Aurora and VEGF receptor (VEGFR) kinases. Patients with advanced solid tumours participated in a phase 1 dose-escalation trial to profile the safety, tolerability, and pharmacokinetics of ilorasertib. METHODS: Ilorasertib monotherapy was administered at 10-180 mg orally once daily (Arm I, n = 23), 40-340 mg orally twice daily (Arm II, n = 28), or 8-32 mg intravenously once daily (Arm III, n = 7), on days 1, 8, and 15 of each 28-day cycle...
March 19, 2018: British Journal of Cancer
Massimo Puoti, Graham R Foster, Stanley Wang, David Mutimer, Edward Gane, Christophe Moreno, Ting Tsung Chang, Samuel S Lee, Rui Marinho, Jean-Francois DuFour, Stanislas Pol, Christophe Hezode, Stuart C Gordon, Simone I Strasser, Paul J Thuluvath, Zhenzhen Zhang, Sandra Lovell, Tami Pilot-Matias, Federico J Mensa
BACKGROUND AND AIMS: Glecaprevir plus pibrentasvir (G/P) is a pangenotypic, once-daily, ribavirin-free direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection. In nine phase 2 or 3 clinical trials, G/P achieved sustained virologic response 12 weeks post-treatment (SVR12) rates of 93-100% across all six major HCV genotypes (GTs). An integrated efficacy analysis of 8- and 12-week G/P in non-cirrhotic patients with HCV GT1-6 infection was performed. METHODS: Data were pooled from nine phase 2 and 3 trials and included patients with chronic HCV GT 1, 2, 3, 4, 5 or 6 infection without cirrhosis who received G/P (300mg/120mg) for either 8 or 12 weeks...
March 15, 2018: Journal of Hepatology
Jeeyun Lee, Seung Tae Kim, Sungju Park, Sujin Lee, Se Hoon Park, Joon Oh Park, Ho Yeong Lim, Hongmo Ahn, Haesook Bok, Kyoung-Mee Kim, Myung Ju Ahn, Won Ki Kang, Young Suk Park
BACKGROUND: Samsung Advance Institute of Technology-301 (SAIT301) is a human immunoglobulin G2 antibody that can specifically target mesenchymal epithelial transition factor (c-MET). This novel antibody has higher priority over hepatocyte growth factors when binding to the Sema domain of c-MET and accelerates the internalization and degradation of c-MET, proving its powerful antitumor activities in intra- as well as extracellular areas. MATERIALS AND METHODS: SAIT301 was administered intravenously once every 3 weeks in c-MET overexpressed solid tumor patients, focusing on metastatic colorectal cancer (CRC) according to common clinical phase I criteria...
January 31, 2018: Clinical Colorectal Cancer
Mitchell E Menezes, Praveen Bhoopathi, Anjan K Pradhan, Luni Emdad, Swadesh K Das, Chunqing Guo, Xiang-Yang Wang, Devanand Sarkar, Paul B Fisher
Subtraction hybridization identified genes displaying differential expression as metastatic human melanoma cells terminally differentiated and lost tumorigenic properties by treatment with recombinant fibroblast interferon and mezerein. This approach permitted cloning of multiple genes displaying enhanced expression when melanoma cells terminally differentiated, called melanoma differentiation associated (mda) genes. One mda gene, mda-7, has risen to the top of the list based on its relevance to cancer and now inflammation and other pathological states, which based on presence of a secretory sequence, chromosomal location, and an IL-10 signature motif has been named interleukin-24 (MDA-7/IL-24)...
2018: Advances in Cancer Research
N Touati, P Schöffski, S Litière, I Judson, S Sleijfer, W T van der Graaf, A Italiano, N Isambert, T Gil, J Y Blay, D Stark, T Brodowicz, S Marréaud, A Gronchi
AIMS: Epithelioid sarcoma is a soft tissue sarcoma associated with a high rate of local recurrence after wide resection and high incidence of distant metastasis. Little is known about the clinical course and response to systemic treatments in epithelioid sarcoma patients. We carried out a retrospective analysis of clinical data from epithelioid sarcoma patients to provide a reference for the design of future epithelioid sarcoma-specific studies. PATIENTS AND METHODS: Data from patients with epithelioid sarcoma entered in prospective multi-sarcoma phase II/III trials were pooled: EORTC trial 62012 (doxorubicin versus doxorubicin/ifosfamide), 62043 (pazopanib), 62072 (pazopanib versus placebo) and 62091 (doxorubicin versus trabectedin)...
March 15, 2018: Clinical Oncology: a Journal of the Royal College of Radiologists
Charu Aggarwal, Andrew R Haas, Susan Metzger, Laura K Aguilar, Estuardo Aguilar-Cordova, Andrea G Manzanera, Gregoria Gómez-Hernández, Sharyn I Katz, Evan W Alley, Tracey L Evans, Joshua M Bauml, Roger B Cohen, Corey J Langer, Steven M Albelda, Daniel H Sterman
Gene-mediated cytotoxic immunotherapy (GMCI) is an immune strategy implemented through local delivery of an adenovirus-based vector expressing the thymidine kinase gene (aglatimagene besadenovec, AdV-tk) followed by anti-herpetic prodrug valacyclovir. A phase I dose escalation trial of GMCI followed by chemotherapy was conducted in patients with malignant pleural effusion (MPE). AdV-tk was administered intrapleurally (IP) in three cohorts at a dose of 1 × 1012 to 1013 vector particles. Primary endpoint was safety; secondary endpoints included response rate, progression-free survival, and overall survival...
February 21, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Michail E Keramidas, Roger Kölegård, Ola Eiken
Cold and hypoxia constitute the main environmental stressors encountered on the Antarctic Plateau. Hence, we examined whether central and/or peripheral acclimatisation to the combined stressors of cold and hypoxia would be developed in four men following an 11-day man-hauling expedition on this polar region. Before and after the journey, participants performed a static whole-body immersion in 21 °C water, during which they were breathing a hypoxic gas (partial pressure of inspired O2 : ~97 mmHg). To evaluate their local responses to cold, participants also immersed the hand into 8 °C water for 30 min, while they were whole-body immersed and mildly hypothermic [i...
April 2018: Journal of Thermal Biology
Chuanpu Hu, Zhenling Yao, Yang Chen, Bruce Randazzo, Liping Zhang, Zhenhua Xu, Amarnath Sharma, Honghui Zhou
Guselkumab, a human IgG1 monoclonal antibody that blocks interleukin-23, has been evaluated in one Phase 2 and two Phase 3 trials in patients with moderate-to-severe psoriasis, in which disease severity was assessed using Psoriasis Area and Severity Index (PASI) and Investigator's Global Assessment (IGA) scores. Through the application of landmark and longitudinal exposure-response (E-R) modeling analyses, we sought to predict the guselkumab dose-response (D-R) relationship using data from 1459 patients who participated in these trials...
March 16, 2018: Journal of Pharmacokinetics and Pharmacodynamics
Myrna R Nahas, Robert J Soiffer, Haesook T Kim, Edwin Alyea, Jon Arnason, Robin Joyce, Joseph H Antin, Vincent Ho, Dina Stroopinsky, Shuli Li, James D Levine, Malgorzata McMasters, Salvia Jain, Ayad Hamdan, Dimitrios Tzachanis, Mary Paty Bryant, Emma Logan, Josie Bazemore, Jeremy Stewart, Amy Joyce, Susan Stephenson, Abigail Washington, Leandra Cole, Athalia Pyzer, Rebecca Karp Leaf, David Avigan, Jacalyn Rosenblatt
Steroid-refractory chronic graft-versus-host disease (SR-cGVHD) remains a major cause of morbidity and mortality following allogeneic transplantation. Innovative immunotherapeutic strategies are urgently needed for the treatment of SR-cGVHD. We conducted a phase I clinical trial to evaluate the safety, efficacy, and immune effects of abatacept, a novel immunomodulatory drug that acts as an inhibitor of T cell activation via co-stimulatory blockade, in the treatment of SR-cGVHD. The study followed a 3+3 design with two escalating abatacept doses: 3 mg/kg and 10 mg/kg, with an expansion cohort treated at 10 mg/kg...
March 16, 2018: Blood
Lech-Gustav Milroy, Bartjan Koning, Daphne S V Scheppingen, Nynke G L Jager, Jos H Beijnen, Jan Koek, Luc Brunsveld
Z-Endoxifen is widely regarded as the most active metabolite of tamoxifen, and has recently demonstrated a 26.3% clinical benefit in a phase I clinical trial to treat metastatic breast cancer after the failure of standard endocrine therapy. Future pharmacological and pre-clinical studies of Z-endoxifen would benefit from reliable and efficient synthetic access to the drug. Here, we describe a short and efficient, stereoselective synthesis of Z-endoxifen capable of delivering multi-gram (37 g) quantities of the drug in >97% purity with a Z/E ratio >99% after trituration...
March 13, 2018: Bioorganic & Medicinal Chemistry Letters
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"