Phase III clinical trial

BACKGROUND: The standard postsurgical options for low-grade gliomas include watchful waiting or radiotherapy depending on the risk factors for recurrence. The use of chemotherapy for the treatment of this disease is generally controversial, although the recently published results of the first of two large randomized phase III clinical trials (RTOG 9802 a EORTC 22033-26033), focusing on the evaluation of chemotherapy for the upfront treatment of newly diagnosed low-grade gliomas, are reassuring in this respect...

BACKGROUND: The optimal treatment for low-grade gliomas remains controversial. Neurosurgery, radiotherapy, and chemotherapy are the main treatment options. Despite advances in oncology, there are still a lot of uncertainties, and the optimal sequences, combinations, and timings of these procedures have not yet been optimized. It is still unclear whether temozolomide can replace effective, but toxic PCV chemotherapy (procarbazine, lomustine, vincristine) and whether temozolomide can be used upfront alone instead of radiotherapy alone...

OBJECTIVES: A relationship between reduced brain tissue oxygenation and poor outcome following severe traumatic brain injury has been reported in observational studies. We designed a Phase II trial to assess whether a neurocritical care management protocol could improve brain tissue oxygenation levels in patients with severe traumatic brain injury and the feasibility of a Phase III efficacy study. DESIGN: Randomized prospective clinical trial. SETTING: Ten ICUs in the United States...

PURPOSE: We conducted a meta-analysis of published clinical trials to determine the relationship between the risks of pneumonitis and pneumonitis-related death and programmed cell death-1 (PD-1) inhibitor treatment in patients with cancer. MATERIALS AND METHODS: We examined clinical trials from the Medline and Google Scholar databases. Data from original studies and review articles were also cross-referenced and evaluated. Randomized Phase II and Phase III trials of pembrolizumab and nivolumab treatment in patients with cancer were eligible for the analysis...

BACKGROUND: Asymptomatic left ventricular (LV) dysfunction is highly prevalent in type 2 diabetes patients. Unlike the other hypoglycemic drugs, SGLT2 inhibitors have shown potential benefits for reducing cardiovascular death and risk factors, aside from lowering plasma glucose levels. With this study we aim at determining whether the treatment with empagliflozin is associated with an improvement in LV functions in diabetic patients with asymptomatic LV dysfunction against Sitagliptin, which is presumably neutral on myocardial function...

Inhibition of autophagy is a promising strategy for non-small cell lung cancer (NSCLC) treatment, which is in the clinical trials. However, only chloroquine is used in clinic as an autophagic inhibitor and the inhibitory effect of chloroquine on autophagy is finite. Therefore, the development of an alternative autophagic inhibitor for NSCLC therapy becomes necessary. In the present study, cepharanthine (CEP), an alkaloid extracted from Stephania cepharantha Hayata, was identified as a novel autophagic inhibitor in NSCLC cells...

OBJECTIVE: Deutetrabenazine is a deuterated formulation of tetrabenazine. The aim of this systematic review is to describe the efficacy, tolerability and safety of deutetrabenazine for the treatment of tardive dyskinesia (TD). DATA SOURCES: The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/ and http://www.clinicaltrials.gov, for the search terms 'deutetrabenazine' OR 'SD-809', and by also querying the EMBASE (Elsevier) commercial database for clinical poster abstracts, and by asking the manufacturer for copies of posters presented at congresses...

BACKGROUND: Few studies explore stroke survivor views and motivations towards stem cell therapy (SCT). This qualitative study explores the views and motivations of both stroke survivors and their partners/carers towards a proposed 2-arm Phase III Randomised Controlled Trial (RCT) comparing intracerebral insertion of stem cells with placebo neurosurgery in stroke survivors with disability. OBJECTIVE: To explore views and motivations towards a proposed 2-arm stem cell trial and identify factors that may impede and enhance participation...

Purpose Nivolumab, a programmed death-1 inhibitor, prolonged overall survival compared with docetaxel in two independent phase III studies in previously treated patients with advanced squamous (CheckMate 017; ClinicalTrials.gov identifier: NCT01642004) or nonsquamous (CheckMate 057; ClinicalTrials.gov identifier: NCT01673867) non-small-cell lung cancer (NSCLC). We report updated results, including a pooled analysis of the two studies. Methods Patients with stage IIIB/IV squamous (N = 272) or nonsquamous (N = 582) NSCLC and disease progression during or after prior platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m(2) every 3 weeks)...

Background: Studies indicate that the prevalence of multi-drug resistant infections, including hospital acquired and ventilator associated bacterial pneumonia (HABP/VABP), has been rising. There are many challenges associated with these disease conditions and the ability to develop new treatments. Additionally, HABP/VABP clinical trials are very costly to conduct given their complex protocol designs and the difficulty in recruiting and retaining patients. Methodology: With input from clinicians, representatives from industry, and the Food and Drug Administriation (FDA), we conducted a study to (1) evaluate the drivers of HABP/VABP phase 3 direct and indirect clinical trial costs, (2) to identify opportunities to lower these costs, and (3) to compare (1) and (2) to endocrine and oncology clinical trials...

The introduction of combination antiretroviral therapy (ART) in the 1990s has fundamentally transformed the landscape of HIV medicine, greatly improved disease morbidity and mortality, and reduced transmission rates across all demographic groups. Central to this success was the idea that to achieve best disease outcomes and minimize the development of drug resistance, at least three antiretroviral agents should be used for HIV treatment. This therapeutic strategy is a core tenet of HIV medicine, backed by incontrovertible scientific evidence, and made easy to deploy by the high compliance levels with once-daily coformulations, which have generally been well tolerated...

BACKGROUND: This phase III study was undertaken to evaluate the efficacy of an allogeneic whole-cell vaccine (Canvaxin™) plus bacillus Calmette-Guerin (BCG) after complete resection of stage IV melanoma. METHODS: After complete resection of ≤5 distant metastases, patients were randomly assigned to BCG+Canvaxin (BCG/Cv) or BCG+placebo (BCG/Pl). The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS), and immune response measured by skin test (ClinicalTrials...

600 patients aged ≥18 years will be randomised in a 1:1 ratio to nintedanib or placebo. Patients with diagnosis of IPF will be excluded. The study population will be enriched with two-thirds having a usual interstitial pneumonia-like pattern on HRCT. The primary endpoint is the annual rate of decline in forced vital capacity over 52 weeks. The main secondary endpoints are the absolute change from baseline in King's Brief Interstitial Lung Disease Questionnaire total score, time to first acute interstitial lung disease exacerbation or death and time to all-cause mortality over 52 weeks...

The development of CETP inhibitors has had a long and difficult course with three compounds failing in phase III clinical trials. Finally, the REVEAL trial has shown that the CETP inhibitor anacetrapib decreased coronary heart disease when added to statin therapy. While the result is different to earlier studies, this is likely related to the size and duration of the trial. The benefit of anacetrapib appears to be largely explained by lowering of non-HDL cholesterol, rather than increases in HDL cholesterol...

OBJECTIVE: To review the pharmacology, safety, and efficacy of nintedanib for the treatment of idiopathic pulmonary fibrosis (IPF). METHODS: A literature search was conducted via PubMed using the MeSH term "idiopathic pulmonary fibrosis" combined with the key word "nintedanib." Additional online searches using Google Scholar, Micromedex, and PubMed were performed to obtain prescribing and cost information. RESULTS: One phase II and 2 replicate phase III clinical trials that examined the safety and efficacy of nintedanib for IPF were identified...

BACKGROUND: Rates of response and remission are measures that endorse the clinical significance of treatment. Cariprazine is FDA approved for the acute treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adults. Post hoc analyses of pooled data from 3 pivotal trials of cariprazine in manic/mixed episodes associated with bipolar I disorder were conducted to investigate the effect of cariprazine on various criteria of response and remission. METHODS: The constituent studies were 3-week randomized, double-blind, placebo-controlled, multicenter, parallel-group phase II/III studies in adult patients (age 18-65 years) with bipolar I disorder (NCT00488618, NCT01058096, NCT01058668)...

Background: Glioblastoma is the most common primary malignant brain tumor in adults, but effective therapies are lacking. With the scarcity of positive phase III trials, which are increasing in cost, we examined the ability of positive phase II trials to predict statistically significant improvement in clinical outcomes of phase III trials. Methods: A PubMed search was conducted to identify phase III clinical trials performed in the past 25 years for patients with newly diagnosed or recurrent glioblastoma...

PURPOSE: The ASCO value framework allows physicians and patients to compare the relative value of novel treatments. Our aim was to assess the value of three frontline ovarian cancer therapies by using this framework. METHODS: From phase III, randomized controlled clinical trial (RCT) data, the net health benefits (NHBs) for three frontline ovarian cancer treatment options-dose-dense paclitaxel (Japanese Gynecologic Oncology Group study JGOG 3016), intraperitoneal (IP)/intravenous (IV) chemotherapy (Gynecologic Oncology Group [GOG] study GOG 172), and concurrent plus maintenance bevacizumab (GOG 218 and the Seventh International Collaborative Ovarian Neoplasm study [ICON7])-were calculated...

Until recently, there has been little advancement in the management of invasive and metastatic urothelial cancer in over 30 years, and outcomes with cisplatin-based chemotherapy remain unchanged. Inhibitors targeting PD-1 signaling on cytotoxic T-cells have revolutionized bladder cancer therapy leading to durable responses. Atezolizumab is an engineered humanized anti-PD-L1 monoclonal antibody that inhibits PD-L1 binding to PD-1 and B7.1, enhancing immune-mediated tumor killing and is currently approved as second-line treatment after failure of platinum-based chemotherapy as well as first-line in cisplatin-ineligible patients...

The rapid progress of genetic engineering furthermore opens up new prospects in the therapy of this difficult-to-treat disease. IL-23 inhibitors, phosphodiesterase 4 (PDE4) inhibitors, and Janus kinase (JAK) inhibitors are currently encouraging further research. Two drugs which are IL-23 inhibitors are now in phase III of clinical trials. The aim of the action of both drugs is selective IL-23 inhibition by targeting the p19 subunit. Guselkumab is a fully human monoclonal antibody. Tildrakizumab is a humanized monoclonal antibody, which also belongs to IgG class and is targeted to subunit p19 of interleukin 23 (IL-23)...