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Phase III trials

Natasha A Lannin, Louise Ada, Coralie English, Julie Ratcliffe, Maria Crotty
Rationale Although clinical practice guidelines recommend that management of moderate to severe spasticity include the use of botulinum toxin-A in conjunction with therapy, there is currently no evidence to support the addition of therapy. Aims To determine the effect and cost-benefit of adding evidence-based movement training to botulinum toxin-A. Sample size estimate A total of 136 participants will be recruited in order to be able to detect a between-group difference of seven points on the Goal Attainment Scale T-score with 80% power at a two-tailed significance level of 0...
January 1, 2018: International Journal of Stroke: Official Journal of the International Stroke Society
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
Asher Haug-Baltzell, Tushar R Bhangale, Diana Chang, Amy Dressen, Brian L Yaspan, Ward Ortmann, Matthew J Brauer, Julie Hunkapiller, Jens Reeder, Kiran Mukhyala, Karen T Cuenco, Jennifer A Tom, Amy Cowgill, Jan Vogel, William F Forrest, Timothy W Behrens, Robert R Graham, Arthur Wuster
In clinical trials, a placebo response refers to improvement in disease symptoms arising from the psychological effect of receiving a treatment rather than the actual treatment under investigation. Previous research has reported genomic variation associated with the likelihood of observing a placebo response, but these studies have been limited in scope and have not been validated. Here, we analyzed whole-genome sequencing data from 784 patients undergoing placebo treatment in Phase III Asthma or Rheumatoid Arthritis trials to assess the impact of previously reported variation on patient outcomes in the placebo arms and to identify novel variants associated with the placebo response...
March 18, 2018: Genes and Immunity
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
Leo F Buckley, Antonio Abbate
Interleukin-1 (IL-1) is the prototypical pro-inflammatory cytokine that occupies an apical place in the inflammatory cascade and also modulates cardiac function, functioning as a soluble cardiodepressant factor. Preclinical research over the past 4 decades has shown that blocking IL-1 processing or activity favorably affects cardiomyocyte survival and cardiac function in experimental animal models, paving the way for clinical studies in patients with heart disease. The promising results of phase II clinical trials of IL-1 blockade in patients with acute myocardial infarction and heart failure have been followed by a successful phase III trial in patients with prior acute myocardial infarction...
March 16, 2018: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
Deborah A Hall, Alberto R Ramos, Jeffrey Marc Gelfand, Aleksander Videnovic, Michael Benatar, Carolyn Cahill, Benzi M Kluger, Myla Goldman
OBJECTIVE: To study and provide an update on the state of clinical research in neurology in the United States. METHODS: US American Academy of Neurology members and chairs of departments of neurology were surveyed regarding clinical research in 2016. NIH data on the neuroscience pipeline and extramural grant funding were also collected. RESULTS: The response rate was 32% (n = 254) for nonchair researchers and 58% (n = 67) for department chairs...
March 16, 2018: Neurology
Young-A Heo, Emma D Deeks
A fixed-dose combination of the hepatitis C virus (HCV) NS5B polymerase inhibitor sofosbuvir, the HCV NS5A inhibitor velpatasvir and the HCV NS3/4A protease inhibitor voxilaprevir (sofosbuvir/velpatasvir/voxilaprevir; Vosevi® ) is approved in the EU for the treatment of chronic HCV genotype 1, 2, 3, 4, 5 or 6 infection in adults. In the phase III POLARIS trials, in patients who had HCV genotype 1-6 infection with or without compensated cirrhosis, overall rates of sustained virological response at 12 weeks post-treatment (SVR12 ) with sofosbuvir/velpatasvir/voxilaprevir were high after 8 weeks of treatment in direct-acting antiviral (DAA)-naïve patients and 12 weeks of treatment in DAA-experienced patients...
March 15, 2018: Drugs
Hao Hu, Qian Zhu, Xian Shi Luo, Xiong Wen Yang, Hai Dong Wang, Chang Ying Guo
Background: Programmed cell death 1 (PD-1) and programmed cell death-ligand 1(PD-L1) inhibitors have captured our attention as new therapeutic options for several tumor types. Nonetheless, the differences in efficacy between PD-1/PD-L1 inhibitors and conventional treatments (chemotherapy or targeted therapy) in pretreated advanced cancer patients remain unclear. Materials and Methods: A systematic literature search was conducted to identify phase III randomized controlled trials (RCTs)-based investigations of PD-1(nivolumab, pembrolizumab)/PD-L1 inhibitors (atezolizumab) against pretreated advanced cancer...
February 20, 2018: Oncotarget
Barry H Smith, Lawrence S Gazda, Thomas J Fahey, Angelica Nazarian, Melissa A Laramore, Prithy Martis, Zoe P Andrada, Joanne Thomas, Tapan Parikh, Sudipta Sureshbabu, Nathaniel Berman, Allyson J Ocean, Richard D Hall, David J Wolf
Objective: The complexity, heterogeneity and capacity of malignant neoplastic cells and tumors for rapid change and evolution suggest that living-cell-based biological-systems approaches to cancer treatment are merited. Testing this hypothesis, the tumor marker, metabolic activity, and overall survival (OS) responses, to the use of one such system, implantable macrobeads [RENCA macrobeads (RMBs)], in phase I and IIa clinical trials in advanced, treatment-resistant metastatic colorectal cancer (mCRC) are described here...
February 2018: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
Darren M Brenner, Ronald Fogel, Spencer D Dorn, Richard Krause, Paul Eng, Robert Kirshoff, Anhthu Nguyen, Robert A Crozier, Leslie Magnus, Patrick H Griffin
OBJECTIVES: Two identical, phase 3, randomized, double-blind, placebo-controlled trials evaluated the efficacy and safety of plecanatide in patients with irritable bowel syndrome with constipation (IBS-C). METHODS: Adults meeting Rome III criteria for IBS-C were randomized (1:1:1) to placebo or plecanatide (3 or 6 mg) for 12 weeks. The primary efficacy end point was the percentage of overall responders (patients reporting ≥30% reduction from baseline in worst abdominal pain plus an increase of ≥1 complete spontaneous bowel movement (CSBM)/week from baseline in the same week for ≥6 of 12 treatment weeks)...
March 15, 2018: American Journal of Gastroenterology
Bryce Chiang, Jaehwan Jung, Mark Prausnitz
The suprachoroidal space (SCS) is a potential space between the sclera and choroid that traverses the circumference of the posterior segment of the eye. The SCS is an attractive site for drug delivery because it targets the choroid, retinal pigment epithelium and retina with high bioavailability, while maintaining low levels elsewhere in the eye. Indeed, phase III clinical trials are investigating the safety and efficacy of SCS drug delivery. Here, we review the anatomy and physiology of the SCS; methods to access the SCS; kinetics of SCS drug delivery; strategies to target within the SCS; current and potential clinical indications; and the safety and efficacy of this approach in preclinical animal studies and clinical trials...
March 12, 2018: Advanced Drug Delivery Reviews
C Wilson, R Bell, S Hinsley, H Marshall, J Brown, D Cameron, D Dodwell, R Coleman
The fracture impact of adjuvant bisphosphonates in breast cancer is not defined with most trials reporting changes in bone mineral density as a surrogate. The AZURE trial (ISRCTN79831382) evaluated the impact of adjuvant zoledronic acid (ZOL) on fractures. The AZURE trial is an academic, multi-centre, randomised phase III study evaluating the addition of ZOL 4 mg to standard therapy (neo/adjuvant chemotherapy and/or endocrine therapy) for 5 years (administered by intravenous (iv) infusion every 3-4 weeks for 6 doses, then 3 monthly × 8 and 6 monthly × 5) in patients with stage II/III early breast cancer...
March 12, 2018: European Journal of Cancer
Michael Untch, Gunter von Minckwitz, Bernd Gerber, Christian Schem, Mahdi Rezai, Peter A Fasching, Hans Tesch, Holm Eggemann, Claus Hanusch, Jens Huober, Christine Solbach, Christian Jackisch, Georg Kunz, Jens-Uwe Blohmer, Maik Hauschild, Tanja Fehm, Valentina Nekljudova, Sibylle Loibl
Purpose The GeparQuinto phase III trial demonstrated a lower pathologic complete response (pCR; pT0 ypN0) rate when lapatinib was added to standard anthracycline-taxane chemotherapy compared with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer. Here, we report the long-term outcomes. Methods Patients with HER2-positive tumors (n = 615) received neoadjuvant treatment with epirubicin (E) plus cyclophosphamide (C), followed by docetaxel (T) in combination with either lapatinib (L) or trastuzumab (H; ECH-TH arm: n = 307; ECL-TL arm: n = 308)...
March 15, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Raches Ella, Radhika Bobba, Sanjay Muralidhar, Sudhir Babji, Krishna Mohan Vadrevu, Maharaj Kishan Bhan
BACKGROUND: The World Health Organization recommends that rotavirus vaccines should be included in all national immunization programs. Some currently licensed oral rotavirus vaccines contain a buffering agent (either as part of a ready-to-use liquid formulation or added during reconstitution) to reduce possible degradation of the vaccine virus in the infant gut, which poses several programmatic challenges (the large dose volume or the reconstitution requirement) during vaccine administration...
March 15, 2018: Human Vaccines & Immunotherapeutics
Yuling Wu, Ahmad Akhgar, Jia J Li, Binbing Yu, Cecil Chen, Nancy Lee, Wendy I White, Lorin K Roskos
Assessment of anti-drug antibodies (ADAs) for neutralizing activity is important for the clinical development of biopharmaceuticals. Two types of neutralizing antibody (NAb) assays (competitive ligand-binding assay [CLBA] and cell-based assay [CBA]) are commonly used to characterize neutralizing activities. To support the clinical development of benralizumab, a humanized, anti-interleukin-5 receptor α, anti-eosinophil monoclonal antibody, we developed and validated a CLBA and a CBA. The CLBA and CBA were compared for sensitivity, drug tolerance, and precision to detect NAbs in serum samples from clinical trials...
March 14, 2018: AAPS Journal
Junichiro Kawamura, Fumiaki Sugiura, Yasushi Sukegawa, Yasumasa Yoshioka, Jin-Ichi Hida, Shoichi Hazama, Kiyotaka Okuno
The safety and immunological responsiveness of a peptide vaccine of ring finger protein 43 and 34-kDa translocase of the outer mitochondrial membrane combined with uracil-tegafur/leucovorin (UFT/LV) was previously demonstrated in metastatic colorectal cancer (CRC) in a phase I clinical trial. To clarify the survival benefit of a peptide vaccine combined with UFT/LV as adjuvant treatment, a phase II clinical trial was conducted involving patients with stage III CRC. All enrolled patients, whose human leukocyte antigen (HLA)-A status was double-blinded, were administered the same regime of a peptide vaccine and UFT/LV chemotherapy...
April 2018: Oncology Letters
Yan Xue, Xianghong Qin, Liya Zhou, Sanren Lin, Ling Wang, Haitang Hu, Jielai Xia
AIM AND BACKGROUND: Proton pump inhibitors (PPIs) are the main drugs for the treatment of reflux esophagitis. Phase II clinical trials showed that, compared with Esomeprazole, the new PPI Ilaparazole is great in terms of efficacy for reflux symptoms relief and curling for esophagitis. The aim of this study was to confirm suitable dose of Ilaparazole in the treatment of reflux esophagitis. METHODS: This study used a randomized, double-blind, parallel positive drug control, multi-center design...
March 11, 2018: Contemporary Clinical Trials
Kevin Zarrabi, Shenhong Wu
BACKGROUND: Nivolumab is approved for the treatment of many cancers. This meta-analysis was conducted to determine the risk of hepatotoxicity with nivolumab therapy. METHODS: An analysis from all phase I-III clinical trials up to December 2016 examining nivolumab was conducted. Data on elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were extracted from the safety profiles of each trial. Incidence and relative risk (RR) were calculated using random- or fixed-effects models with 95% confidence intervals (CIs)...
March 14, 2018: Oncology
Sandro Virgilio Porceddu, Mathias Bressel, Michael Geoffrey Poulsen, Adam Stoneley, Michael John Veness, Lizbeth Moira Kenny, Chris Wratten, June Corry, Stephen Cooper, Gerald Blaise Fogarty, Marnie Collins, Michael Kevin Collins, Andrew Martin John Macann, Christopher Gerard Milross, Michael Gordon Penniment, Howard Yu-Hao Liu, Madeleine Trudy King, Benedict James Panizza, Danny Rischin
Purpose To report the results of the Trans Tasman Radiation Oncology Group randomized phase III trial designed to determine whether the addition of concurrent chemotherapy to postoperative radiotherapy (CRT) improved locoregional control in patients with high-risk cutaneous squamous cell carcinoma of the head and neck. Patients and Methods The primary objective was to determine whether there was a difference in freedom from locoregional relapse (FFLRR) between 60 or 66 Gy (6 to 6.5 weeks) with or without weekly carboplatin (area under the curve 2) after resection of gross disease...
March 14, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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