Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.4.1-1 | Award Amount: 7.74M | Year: 2011
Though survival of children with acute lymphoblastic leukaemia (ALL) has improved, relapse remains a leading cause of mortality in childhood cancer. Given the rarity of the disease, only a large international cooperative group can recruit sufficient patients for prospective studies with specific questions in biologic subgroups. Under the umbrella of the I-BFM SG all relevant mainly European study groups are creating the worldwide largest Study for Children with Relapsed ALL (IntReALL 2010). The aim is to develop optimized standard treatment as platform for systematic randomized phase II and III studies on the most promising new and targeted agents. An adequate trial structure, an optimized web based database, and standardized diagnostic methods need to be established. Patients are stratified into a standard (SR) and a high risk (HR) group according to established factors. For SR patients, the best available treatment protocols ALL-REZ BFM 2002 and ALL R3 are randomly compared, and the additional effect on survival of the humanized monoclonal CD22 directed antibody epratuzumab is investigated. HR patients who have unsatisfying remission rates will receive an intensified induction with the new nucleoside analogue clofarabine compared to standard induction therapy. IntReALL 2010 allows for comprehensive tumour banking and systematic biologic research in subgroups with correlation to clinical outcome. SMEs will be involved into project management, data base development, and pharmaceutical and biotechnological research to ensure innovation in the respective areas. IntReALL 2010 is embedded in a network of European academic structures relevant for childhood cancer. It will be a cornerstone of drug development in childhood leukaemia and the only trial with the potential for well powered phase III studies in this indication. IntReALL 2010 will harmonize ALL-relapse therapy, establish highest diagnostic and therapeutic standard and improve survival of children with ALL.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.4.2-2 | Award Amount: 7.70M | Year: 2014
Coronary artery disease (CAD) is the leading cause of death in high-income countries. Invasive coronary angiography (ICA) is the reference standard for the diagnosis of CAD and allows immediate therapy. However, only 40% of patients undergoing ICA actually have obstructive CAD and ICA has relatively rare but considerable risks. Coronary computed tomography (CT) is the most accurate diagnostic test for CAD currently available. CT may become the most effective strategy to reduce the ca. 2 million annual negative ICAs in Europe by enabling early and safe discharge of the majority of patients with an intermediate risk of CAD. To evaluate this, we propose the DISCHARGE project that will be implemented by a multinational European consortium. The core of the project is the DISCHARGE pragmatic randomised controlled trial. The primary hypothesis will be that CT is superior to ICA for major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and stroke) after a maximum follow-up of 4 years in a selected broad population of stable chest pain patients with intermediate pretest likelihood of CAD. The trial will include 23 clinical sites from 18 European countries ensuring broad geographical representation. Comparative effectiveness research of complementing work packages include gender-related analysis, systematic review of evidence, cost-effectiveness analysis, and health-related quality of life. DISCHARGE has the capability to influence current standards and guidelines as well as coverage decisions and will raise awareness among patients, health care providers, and decision-makers in Europe about the effectiveness and cost-effectiveness of coronary CT angiography.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-14-2015 | Award Amount: 16.00M | Year: 2016
VISION-DMD aims to advance clinical development of the orphan drug VBP15 as a new therapy to revolutionise care for all patients with Duchenne muscular dystrophy (DMD) by 2020, in line with IRDiRC goals. DMD is an incurable, rare muscle wasting disease; boys progressively weaken, lose ambulation and death occurs by early adulthood. Corticosteroids (CS) are widely recognised to increase muscle strength and delay disease progression but global acceptance as standard of care is very variable due to severe side effects. VBP15 is an innovative steroid-like drug designed to retain or better CS efficacy and improve membrane stabilization with reduced or no side effects. VBP15 will increase the therapeutic window to slow disease progression and improve quality of life and lifespan for all DMD patients. Building on positive preclinical and Phase 1 results funded by government grants and international patient groups and based on FDA and EMA advice, VISION-DMD proposes a Phase 2 registration directed clinical programme aimed at an affordable therapy: Phase 2a will study the safety and tolerability of ascending doses of VBP15 in ambulant DMD boys; Phase 2b will demonstrate the efficacy and safety of two doses of VBP15 in young ambulant DMD boys. Both studies will be followed by extension studies for long term safety and efficacy data collection leading to cumulative exposure of up to 2100 drug months. The project proposes the Time to Stand Test as a highly relevant and reliable primary endpoint. Innovative exploratory serum biomarkers and novel wide scale MRI techniques will be used to investigate the VBP15 pharmacodynamics and the effect on muscle cellular pathology. VBP15 will meet the unmet need for better treatment for DMD with widespread acceptance and potentially be used in combination with stratified therapies as they are developed. The Consortium links the leading networks TREAT-NMD and CINRG with ECRIN-ERIC, for trial delivery and regulatory undertakings in Europe/US
Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: Prespecified subgroup analyses from the VELOUR trial
Tabernero J.,Autonomous University of Barcelona |
Van Cutsem E.,Catholic University of Leuven |
Lakomy R.,Masaryk Memorial Cancer Institute |
Prausova J.,Fakultni Nemocnice v Motole |
And 8 more authors.
European Journal of Cancer | Year: 2014
Purpose The antiangiogenic agent aflibercept (ziv-aflibercept in the United States) in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) significantly improved survival in a phase III study of patients with metastatic colorectal cancer (mCRC) previously treated with an oxaliplatin-based regimen. In the present analysis, outcomes were evaluated in prespecified subgroups to assess the consistency of the treatment effect. Methods Patients were randomised to receive FOLFIRI plus aflibercept or placebo every 2 weeks until disease progression or unacceptable toxicity occurred. Efficacy and safety outcomes were analysed with respect to demographic and baseline characteristics, and stratification factors (prior bevacizumab treatment and Eastern Cooperative Oncology Group performance status). Results Median overall survival (OS, months [95.34% confidence interval (CI)]) for aflibercept versus placebo was 12.5 (10.8-15.5) versus 11.7 (9.8-13.8) in patients with prior bevacizumab treatment and 13.9 (12.7-15.6) versus 12.4 (11.2-13.5) in patients with no prior bevacizumab treatment. The p value for interaction was 0.5668, indicating there was no heterogeneity in these subgroups. For OS and progression-free survival (PFS), there was a significantly greater benefit (at the 2-sided 10% level) of treatment for patients with liver only metastases versus patients with no liver metastases/liver metastases with other organ involvement (p value for interaction: 0.0899 [OS]; 0.0076 [PFS]). There was no evidence of heterogeneity in treatment effect in any of the other subgroups examined. Conclusions The benefits of aflibercept in combination with FOLFIRI in patients with mCRC previously treated with oxaliplatin were maintained across the specified patient subgroups, including in patients with or without prior bevacizumab treatment. © 2013 Elsevier Ltd. All rights reserved.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-18-2015 | Award Amount: 8.19M | Year: 2016
Liver cancer in the paediatric population is rare with an incidence approximately 1-1.5 per million population. The commonest tumour seen in the childhood population is hepatoblastoma (HB), usually seen in young children and infants. Much rarer (about 10% of paediatric liver cancers) is hepatocellular carcinoma (HCC), usually seen in the teenage population and sometimes associated with underlying cirrhotic liver diseases. The ChiLTERN project relates to topic PHC 18 establishing effectiveness of health care interventions in the paediatric population. The ChiLTERN project builds on a unique opportunity to undertake a comprehensive research programme linked to an ambitious global partnership which will see the single largest clinical trial (the Paediatric Hepatic International Tumour Trial - PHITT) ever undertaken in this population of patients, with several randomised questions in six subgroups of patients. ChiLTERN will allow us to move towards an era of personalised therapy in which each patient will receive the correct amount of chemotherapy and will undergo has the best surgical operation (surgical resection or liver transplant). By using both clinical and biological information, we can assign patients more accurately to risk groups based on their survival. Using genetic tests and biomarkers, we will determine those children who may be at risk of developing long term side effects (deafness, heart failure, kidney damage). In addition, biomarkers will allow us to monitor during therapy and detect toxicities early before serious damage is done so that we can adapt treatment and prevent these problems. Finally, we will be using imaging technology tools which will help our surgeons plan liver operations more safely and effectively. Ultimately ChiLTERN will allow us to cure more children with liver cancer, expose fewer children to toxic chemotherapy and ensure their surgery is both effective and safe.
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2013.2.2.1-4 | Award Amount: 13.02M | Year: 2013
Despite a great progress in the management of epilepsy, still one third of patients is refractory to available medications. The incidence of epilepsy is highest in infancy and 50% of children experience epilepsy-related comorbidities, such as developmental delay and autism. The development of epilepsy (epileptogenesis), extensively studied in animals, is barely studied in humans, as patients usually present AFTER the seizure onset. EPISTOP is the first prospective study of epileptogenesis in humans, beginning BEFORE seizures and continuing through age 2\ years, permitting detailed analysis of the onset, drug-resistance, and comorbidities of epilepsy. To maximize information derived from the study we have chosen homogenous group of patients with prenatal or early infantile diagnosis of Tuberous Sclerosis Complex (TSC). A clinical randomized study of pre-seizure treatment in TSC infants is a part of the project. The aim of EPISTOP is to examine the risk factors and biomarkers of epilepsy and to identify possible new therapeutic targets to block or otherwise modify epileptogenesis in humans. Biomarker analysis will be performed by a multidisciplinary, systematic approach in three clinical settings: 1/ prospective study of epilepsy development in infants with TSC, including analysis of clinical, neuroimaging, and molecular, blood-derived biomarkers at predefined time points: before the onset of seizures, at the onset of epileptiform discharges on EEG, at seizure onset and at the age of 24 months 2/ prospective study of blood-based biomarkers in infants with TSC treated with antiepileptic drugs prior to seizure onset in comparison to children treated only after clinical seizures appearance. 3/ analysis of biomarkers of epileptogenesis and drug-resistant epilepsy in brain specimens obtained from TSC patients who have had epilepsy surgery and TSC autopsy cases. EPISTOP will be carried out by a consortium of 14 partners from 9 countries, including 2 SMEs.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.4.1-3 | Award Amount: 7.81M | Year: 2013
Survival rates after childhood cancer now reach nearly 80% in developed European countries as a result of more effective therapies and better supportive care, leading to a steady increase in the number of survivors in the population. However, the treatments that have improved survival are harsh and cause serious side-effects that can greatly impact survivors quality of life in the long term. The goal of PanCareLIFE is that survivors of cancer diagnosed before age 25 should enjoy the same quality of life and opportunities as their peers who have not had cancer. Using observational studies and molecular genetic investigations PanCareLIFE will investigate late effects that impact fertility and hearing impairment (ototoxicity), and will assess health-related quality of life. Information from PanCareLIFEs studies will be incorporated into new guidelines for fertility preservation. As the number of survivors with late effects in any one country is small, large cohorts are required for accurate estimation of risk. PanCareLIFE has assembled a team of prominent investigators from 8 European countries who will contribute in total over 12,000 well-characterised research subjects to identify risk factors, both genetic and non-genetic, linked to decrements in fertility and ototoxicity. Quality-of-life studies will evaluate the impact of fertility and ototoxicity. PanCareLIFE will advance the state-of-the-art in survivorship studies by evaluation of large cohorts with observational and genetic tools that will provide better knowledge of individual risk factors. Survivors can then be stratified into groups benefitting from personalized, evidence-based, care; future patients may expect effective therapies to have less severe side effects, and plans for a seamless transition to long-term follow-up care can be made. These approaches will result in better quality of life for survivors of cancer diagnosed at a young age.
Aflibercept Plus FOLFIRI vs Placebo Plus FOLFIRI in Second-Line Metastatic Colorectal Cancer: a Post Hoc Analysis of Survival from the Phase III VELOUR Study Subsequent to Exclusion of Patients who had Recurrence During or Within 6 Months of Completing Adjuvant Oxaliplatin-Based Therapy
PubMed | Philadelphia University, University of Witwatersrand, University Hospital 12 Of Octubre, Tumor Biology Center and 15 more.
Type: Journal Article | Journal: Targeted oncology | Year: 2016
The aim of this post hoc analysis of the VELOUR study (ClinicalTrials.gov NCT00561470) was to investigate the treatment effect of adding aflibercept to second-line infusional 5-fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) in patientswith metastatic colorectal cancer (mCRC) who had failed any prior oxaliplatin-containing regimen. Adjuvant rapid relapsers (ARR), who were enrolled directly following relapse during or within 6months of completion of oxaliplatin-containing adjuvant chemotherapy (N=124, including 17 patients who also received bevacizumab as part of their adjuvant therapy), were excluded from the original VELOUR intention-to-treat (ITT) population (N=1226). After exclusion of the ARR, overall survival (OS) in the ITT minus ARR (ITT-ARR) population (N=1102) was longer in the aflibercept plus FOLFIRI arm than in the placebo plus FOLFIRI arm [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.68-0.90; median survival difference 1.87months]. In the subgroup of patients assigned to the prior bevacizumab stratum at randomization, OS was numerically longer in the aflibercept plus FOLFIRI arm than in the placebo plus FOLFIRI arm (HR 0.81; 95% CI 0.63-1.04; median survival difference 2.14months). Comparison of the post hoc analysis results with the primary analysis from VELOUR suggests that the inclusion of the directly enrolled ARR may have understated the aflibercept treatment benefit for both bevacizumab-pretreated and bevacizumab-nave patients in the strictly second-line setting although no definitive conclusion may be inferred. The benefit associated with the addition of aflibercept to second-line FOLFIRI in patients with mCRC was observed whatever the timing of first-line disease progression. There were no unexpected safety concerns.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-15-2015 | Award Amount: 6.70M | Year: 2016
Spinal cord injury is a severe and devastating neurological disorder that leaves patients with permanent paralysis of the body. No treatment is available today to regenerate interrupted nerve fibers and repair the damaged spinal cord. The incidence of spinal cord injury is about newly injured 10000 people per year in the EU, and due to an almost normal life expectancy more than 200000 patients are living with a spinal cord injury in the EU. The impact on the individual quality of life is high, and social costs are enormous. Recent preclinical research in animal models succeeded to greatly enhance axonal sprouting, fiber regeneration and neuroplasticity following injuries of brain and spinal cord. These results warrant translation now to patients suffering from acute spinal cord injury. A previous phase I clinical study using intrathecal application of a nerve fiber growth promoting antibody against the growth inhibitory protein Nogo-A has shown in patients with complete spinal cord injury that this treatment is safe and well tolerated. The present study will enroll patients with various degrees of complete to incomplete acute spinal cord injury for a double-blind, placebo-controlled trial to test the efficacy of this antibody therapy to improve motor outcome and quality of life of tetraplegic patients. The enrollment of patients with different degrees of spinal cord injury is considered essential to reveal drug activity and eventual proof of concept in a broad patient population. Advancements in clinical trial design, improved prediction algorithms of clinical outcomes and development of surrogate markers (in cerebro-spinal fluid/serum and by neuroimaging) will allow for scrutinizing the effectiveness of this novel treatment in an unprecedented way. A positive outcome of this trial will represent a breakthrough for the future therapy of spinal cord injuries and beyond (traumatic brain injury, stroke, multiple sclerosis).
Klima K.,Fakultni Nemocnice V Motole
Anesteziologie a Intenzivni Medicina | Year: 2010
In 1970, the new University Children's Hospital was opened in Prague-Motol. The 12-bed Department of Maxillofacial and Dental Surgery for children was the first one to be opened in the former Czechoslovakia. Prof. Jaroslav Komínek, the head of the department, organised an internship programme with the Department of Anaesthesiology for his physician. The head of the anaesthetic department Miloslav Drapka was the founder of paediatric anaesthesiology in Czechoslovakia. The initial attempts at anaesthesia for dental surgery were not very successful. Operations in the buccal cavity without tracheal intubation were very hazardous. The author describes the transition of the intubation technique from orotracheal to nasotracheal with packing of the oropharynx. The author also describes a breathing circuit with a low resistance water valve, premedication, parenteral analgesic sedation for inpatients and oral analgesic sedation for outpatients. Ketamine anaesthesia without intubation enabled the dental surgeons to treat large numbers of children. Information abou the mandatory pre-anaesthetic visit and examination, pre-operative preparation and special anaesthetic procedures is presented.