bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 1/1b multicenter, open-label, dose escalation and dose expansion study to evaluate the safety, pharmacokinetics, immunogenicity, and antitumor activity of MEDI3726 in patients with metastatic, castration-resistant prostate cancer who have received prior treatment with abiraterone or enzalutamide.
Authors: Fleming Mark T. , Cathomas Richard , Petrylak Daniel Peter , Wang Judy Sing-Zan , Bander Neil Harrison , Zammarchi Francesca , van Berkel Patrick H. , Cho Song Hye , Elgeioushi Nairouz , Bothos John , Scheuber Anita , de Bono Johann 
Published: September 2018

TPS5088 Background: Therapeutic advances have recently been achieved for patients with metastatic, castration-resistant prostate cancer (mCRPC) due to abiraterone acetate (ABI) and enzalutamide (ENZ). However, virtually all patients with mCRPC eventually progress in their disease, and further treatment options are limited. Prostate-specific membrane antigen (PSMA) is highly expressed in nearly all prostate cancers, and its expression is highest in mCRPC. MEDI3726 is an antibody-drug conjugate composed of anti-PSMA antibody derived from J591, site-specifically conjugated to the cytotoxic, DNA cross-linking, pyrrolobenzodiazepine dimer. MEDI3726 has demonstrated potent and specific in vitro and in vivo antitumor activity in human prostate cancer-derived preclinical models with different expression levels of PSMA. Methods: This is a first-in-human, phase 1/1b, multicenter, open-label, dose escalation and dose expansion study in patients who have received prior treatment with ABI or ENZ, with or without prior taxane-based chemotherapy in the mCRPC setting (NCT02991911). The primary objectives are to assess safety and tolerability, describe dose-limiting toxicities, and determine the maximum tolerated dose or maximum administered dose of MEDI3726. The secondary objectives are to evaluate MEDI3726 for its antitumor activity (based on a composite response according to RECIST Version 1.1, a reduction in prostate-specific antigen level of 50% or more compared to baseline, or a conversion in the circulating tumor cell count [defined as a reduction from ≥5 cells/7.5 mL blood to < 5 cells/7.5 mL blood]), safety and tolerability in combination with ENZ, pharmacokinetics alone and in combination with ENZ, and immunogenicity. Recruitment is ongoing for this study, which has an estimated total target enrollment of 224 patients. Clinical trial information: NCT02991911.
A randomized phase II study of chemoradiation (CRT) +/- nivolumab (Nivo) with sequential safety evaluations of Nivo +/- lirilumab (Liri) or ipilumumab (Ipi) concomitant with (C) RT in intermediate (IR) and high-risk (HR) head and neck squamous cell carcinoma (HNSCC) (RTOG 3504, NCT02764593).
Authors: Gillison Maura L. , Ferris Robert L. , Zhang Qiang , Colevas A. Dimitrios , Mell Loren K. , Kong Christina , Jordan Richard , Moore Kevin , Truong Minh Tam , Kirsch Claudia , Machtay Mitchell , Curran Walter John , Le Quynh-Thu 
Published: September 2018

TPS6097 Background: Nivolumab (Nivo), a monoclonal antibody to the programmed death-1 (PD-1) immune checkpoint receptor, improved overall survival (OS) for patients (pts) with platinum-refractory, recurrent/metastatic HNSCC compared with standard therapy. A placebo controlled phase IIR trial was designed to investigate the hypothesis that Nivo added to platinum-based CRT will improve progression free survival (PFS) for pts with newly diagnosed IR/HR HNSCC. Methods: Eligibility includes IR HNSCC (p16+, oropharynx T1-2N2b-N3/T3-4N0-3, > 10 pack-years (pys) or T4N0-N3, T1-3N3 ≤ 10 pys) and HR HNSCC (oral cavity, larynx, hypopharynx, or p16(-) oropharynx, stage T1-2N2a-N3 or T3-4N0-3). After safety evaluation in 8 evaluable pts, 176 pts will be randomized (1:1) to cisplatin (40 mg/m2/week X 7) with radiation (IMRT, 70 Gy in 7 weeks) +/- Nivo/placebo (240 mgs q14 days X 5, then 480 mgs q28 X3). Primary endpoint is PFS. Secondary endpoints include OS, acute and chronic toxicity, quality of life and biomarkers (tumor PD-L1 expression; E6/7 seroreactivity and frequency of functional circulating and intraumoral T cells). Parallel with Phase IIR are sequential safety evaluations (see Table) in platinum eligible and ineligible ( > 70 years; ≥3 grade neuropathy; ≥2 hearing loss; or CrCl < 60 ml/min) cohorts (N = 10-20) of Nivo +/- Liri (anti-KIR) or Ipi (anti-CTLA4) concomitant with RT alone, cisplatin-RT or cetuximab-RT platforms followed by 3 months of adjuvant immunotherapy. The primary endpoint is safety and feasibility. With 8 evaluable pts, the probability of treatment assessed as toxic is > 78% when the true toxicity rate is > 45% and treatment assessed tolerable is > 80% if the true toxicity rate is < 20%. Clinical trial information: NCT02764593. [Table: see text]
Phase II trial of ribociclib and everolimus in p16 low anaplastic thyroid cancer (ATC).
Authors: Tawfik Bernard , Gerber David E. , Burtness Barbara , Hughes Randall S. , Myers Larry L. , Sumer Baran D. , Truelson John , Strom Tobin Joel , Kurian Pamela , Saleem Sehresh , Pearson Jean , Zhu Hong , Khan Saad A. 
Published: September 2018

TPS6098 Background: ATC is a rare thyroid cancer with a highly aggressive clinical course. Median OS is 3-4 months and 90% of patients die within 1 year of the diagnosis. There are no effective treatment options in metastatic disease. Targeted therapies to ALK and BRAF are occasionally associated with dramatic responses. Retinoblastoma (Rb) inhibits cell cycle progression and is inactivated by CDK 4/6, which is the target for ribociclib. Nearly all differentiated thyroid cancers are Rb negative, conversely nearly 100% of ATC expresses intact Rb which may be crucial for rapid cell cycle progression. Ribociclib is a CDK 4/6 inhibitors that slows cell cycle progression and DNA replication in tumors with functional Rb. The p16 protein similarly inhibits CDK4/6; if p16 levels are high Rb is phosphorylated and thus inactive. p16 is low in ATC, and from our comprehensive genomic analysis 30% of ATC lacks the p16 gene CDKN2a. Most ATC demonstrates PI3K/Akt/mTOR abnormalities, this pathway represents an attractive target in ATC. The mTOR inhibitor everolimus has shown promising efficacy in ATC cell lines, especially in those with TSC2 mutation whose wild type negatively regulates mTOR. Methods: The combination of everolimus and ribociclib targets mutations/abnormalities that are frequently seen in ATC, and is tolerable based on Phase I/II trial results in the latest arm of the biomarker/oncogene driven ATC Master Protocol . This open-label trial treats metastatic Rb+ ATC patients with p16-/ CDKN2a-. Treatment is ribociclib 400 mg + everolimus 5 mg QD. The primary endpoint is the overall response rate; secondary endpoints are PFS, OS, safety and toxicity. Exploratory objectives include if tissue biomarkers or mutations noted on Next Generation Sequencing correlate for enhanced/impaired response to combination therapy. Simon's two-stage design will be used with the null hypothesis that the true response rate is 5%, this will be tested against a one-sided alternative. In the first stage, 9 patients will be accrued. If no response in these 9 patients, the study will be stopped. Otherwise, 21 additional patients will be accrued for a total of 30. Clinical trial information: NCT02289144.
Biospecimen donors' views about biobank closure.
Authors: Pentz Rebecca D. , Dixon Margie D , Allen Samuel C 
Published: September 2018

TPS6625 Background: The future of biobanks is often uncertain due to sporadic funding. A survey of 456 biobank administrators found that they consider the loss of funding to be either a "massive (40%)" or "moderate (31%)" concern. Only 26% of biobanks reported having a plan in the event of closure (Cadigan et al., Life Sciences, Society and Policy, 2013). Biospecimen donors’ views on how they want their tissue handled following biobank closure is unknown. Our study will be the first to determine how biospecimen donors want their data and biological materials handled if their biobanks were to close. We believe this report of 100 biospecimen donors’ views will be useful to researchers and tissue bank administrators in creating contingency tissue bank closure plans that incorporate biospecimen donors’ perspectives. Methods: We will complete accrual of 100 oncology biospecimen donors (current accrual is 65 patients) at one institution by interviewing them about their views of bank closure and preferences for the handling of their tissue post-closure. The interview asks participants if they have a preference for the handling of their tissue and information in the event of bank closure, and if so, if they prefer transfer of their materials to another tissue bank or destruction. Feelings about closure are captured in three categories: sad/disappointed, angry/frustrated, and other negative emotions. The effect of tissue bank closure upon trust in medical research is captured in three categories: decreases trust, does not decrease trust, and may decrease trust under certain circumstances. We ask the participants to rank the following options for transfer of their tissue and information: transfer to another local academic tissue bank, to a for-profit or pharmaceutical bank, to an international bank, or to a national bank. We also ask if any of these options are deemed absolutely unacceptable. Results: NA Conclusions: NA
Phase 3, randomized, double-blind, placebo-controlled study of venetoclax combined with azacitidine versus azacitidine in treatment-naïve patients with acute myeloid leukemia.
Authors: Potluri Jalaja , Xu Tu , Hong Wan-Jen , Mabry Mack H. 
Published: September 2018

TPS7069 Background: Elderly acute myeloid leukemia (AML) is a biologically and clinically distinct disease with a diminished response to chemotherapy, low remission rates, and short disease-free and overall survival. Venetoclax (VEN) is a potent, selective small-molecular inhibitor of BCL-2. In preclinical models, venetoclax has been shown to kill AML cells as a single agent with demonstrated synergistic activity in combination with the DNA methyltransferase inhibitor azacitidine (AZA). Early clinical data from a phase 1b study (NCT02203773) showed that VEN plus AZA had an acceptable safety profile and promising efficacy in treatment-naïve elderly patients with AML. The current phase 3 study continues to evaluate the combination for this AML population. Methods: This phase 3, randomized, double-blind, placebo-controlled study (NCT02993523) is designed to assess VEN plus AZA compared with placebo plus AZA in treatment-naïve elderly and adult patients with AML who are not eligible for standard induction therapy due to age or comorbidities. Primary objectives of the study are to evaluate if VEN with AZA will improve overall survival (OS) and composite complete remission rate (CR+CRi) versus placebo with AZA. Secondary objectives include event-free survival, CR+CRi rate at the end of Cycle 1, and if combining VEN plus AZA reduces fatigue and improves global health status/quality of life based on patient reported outcomes versus placebo with AZA. Exploratory objectives are to evaluate biomarkers predictive of VEN activity including minimal residual disease negativity rate, and BCL-2 expression and outcome measures of overall survival and complete remission rate, as well as the impact of VEN on additional quality of life measures. Patients will be randomized 2:1 to VEN plus AZA (arm A) or placebo plus AZA (arm B). Patients on arm A will receive once daily 400 mg VEN orally on days 1–28 plus daily 75 mg/m2 SC or IV AZA for 7 days in a 28-day cycle. Patients on arm B will receive once daily placebo orally on days 1–28 plus daily 75 mg/m2 SC or IV AZA for 7 days on a 28-day cycle. Study recruitment began in February 2017, with target enrollment of 400 patients. Clinical trial information: NCT02993523.
Phase 1b/3 study of avelumab-based combination regimens in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).
Authors: Chen Robert W. , Ansell Stephen Maxted , Zinzani Pier Luigi , Vacirca Jeffrey L. , Lopez-Guillermo Armando , Hutchings Martin , Jurczak Wojciech , Hess Georg , Le Gouill Steven , Offner Fritz , Santoro Armando , Salles Gilles A. , Stypinski Daria , Laird Douglas , Pavlov Dmitri , Andreola Giovanna , Fly Kolette D. , Woolfson Adrian , Collins Graham P 
Published: September 2018

TPS7575 Background: Approximately 50% of patients (pts) with advanced DLBCL are refractory to or relapse following first line R-CHOP therapy. Pts with R/R DLBCL have limited treatment options and a poor prognosis. This study assesses immunotherapy-based regimens containing avelumab (a fully human IgG1 anti–PD-L1 antibody) in combination with utomilumab (a novel 4-1BB agonist), azacitidine, rituximab, and/or conventional chemotherapy (CT; bendamustine) in pts with R/R DLBCL. Methods: JAVELIN DLBCL (NCT02951156) is a global, multicenter, randomized, open-label, 2-component(phase 1b followed by phase 3) study of avelumab-based combination regimens in R/R DLBCL. In phase 1b, up to 84 pts will be randomized 1:1:1 to receive avelumab/rituximab/utomilumab, or avelumab/azacitidine/utomilumab, or avelumab/rituximab/bendamustine. The primary phase 1b objectives are preliminary assessments of dose-limiting toxicities (n = 6 per arm) and efficacy (objective response [OR]; n = 28 per arm). One regimen from phase 1b will be selected for phase 3 evaluation in 220 additional pts randomized 1:1 to the chosen regimen or investigator’s choice CT (rituximab/bendamustine or rituximab/gemcitabine/oxaliplatin). The primary phase 3 objective is to demonstrate progression-free survival (PFS) superiority of the avelumab-based regimen over CT. Overall survival is a key secondary endpoint. Eligible pts have completed up to 4 lines of prior rituximab/multiagent CT, and/or have failed autologous stem cell transplantation (ASCT), or are not eligible for intensive CT or ASCT. Other eligibility criteria include ECOG PS ≤1 and no prior therapy with a checkpoint inhibitor. Treatment with avelumab, utomilumab, and azacitidine will be continued until the pt no longer receives clinical benefit; rituximab and bendamustine are limited to 8 and 6 cycles, respectively. OR and PFS will be assessed per Lugano disease classification criteria. Other secondary efficacy endpoints include disease control, duration of response, time to response, and minimal residual disease burden. Safety, PK, immunogenicity, pt-reported outcomes, and biomarkers will also be evaluated. Clinical trial information: NCT02951156.
Randomized, open-label phase Ib/II study of atezolizumab with or without daratumumab in previously treated advanced or metastatic non-small cell lung cancer (NSCLC).
Authors: Pillai Rathi Narayana , Ramalingam Suresh S. , Carbone David P. , Paz-Ares Luis G. , Thayu Meena , Watson Patricia , Khokhar Nushmia Z. , Reck Martin 
Published: September 2018

TPS9102 Background: Daratumumab (DARA), a human CD38 monoclonal antibody, is approved for treatment of relapsed/refractory multiple myeloma (RRMM). DARA produces deep clinical responses in RRMM and induces T-cell expansion through reduction of immune suppressive cell populations (CD38+ myeloid-derived suppressor cells and regulatory T and B cells). Atezolizumab (atezo) blocks programmed death-ligand 1 (PD-L1) and was recently approved for metastatic NSCLC that progressed on or during platinum therapy based on data showing improved overall survival (OS) in the atezo vs docetaxel treatment arm. A combination of DARA and atezo may improve clinical responses in NSCLC by enhancing anti-tumor T-cell responses facilitated by checkpoint inhibition. This study will assess the anti-tumor activity and safety profile of DARA plus atezo vs atezo alone in patients (pts) with previously treated advanced or metastatic NSCLC. Methods: This is an ongoing phase 1b/2 randomized, open-label, multicenter study of atezo (1200 mg intravenous [IV]; Day 2 of Cycle 1 and Day 1 of each 21-day cycle thereafter) alone or in combination with DARA (16 mg/kg IV weekly for 3 cycles [Days 1, 8, and 15] and then Day 1 of each 21-day cycle thereafter). Eligible pts (≥18 years) must have advanced or metastatic NSCLC and received standard platinum-based therapy with disease progression or intolerance to therapy. ECOG performance status of ≤1 and known PD-L1 tumor status are required. Pts previously treated with anti-CD38 therapy, including DARA, CD137 agonists, or immune checkpoint inhibitors are excluded. The primary endpoint is overall response rate. Secondary outcomes include safety, duration of response, clinical benefit rate (≥16 weeks duration), progression-free survival, OS, and pharmacokinetics and immunogenicity of DARA and atezo when given in combination. Approximately 96 pts will be enrolled; 6 pts will receive combination therapy in a safety run-in cohort for evaluation of dose-limiting toxicity followed by 90 pts randomly (1:1) assigned to the 2 treatments. Clinical trial information: NCT03023423.
Phase II clinical trial of atezolizumab (A) in advanced non-small cell lung cancer (NSCLC) patients (pts) previously treated with PD1-directed therapy.
Authors: Bhattacharya Saveri , Yun Cindy , Schulze Katja , Bruno Tullia C. , Kurland Brenda F , Socinski Mark A. , Villaruz Liza Cosca 
Published: September 2018

TPS9105 Background: While inhibition of the PD1 axis is associated with improved response rates vs cytotoxic therapy in pts with previously treated NSCLC, the majority of pts will not benefit from objective response. Anti-PD1 and PD-L1 antibodies block distinct inhibitory pathways, possibly resulting in different clinical outcomes. While anti-PD1 antibodies block PD1 binding to PD-L1 and PD-L2, they do not affect the inhibitory signal of the PD-L1/B7.1 interaction. This trial is critical to establishing the clinical activity of sequencing PD-L1 inhibition in pts previously treated with PD1 directed and identifying candidate biomarkers of response and resistance to PD1/PD-L1 directed therapies. Methods: In this phase II clinical trial, pts with advanced NSCLC with stable or progressive disease on anti-PD1 therapy (nivolumab or pembrolizumab) will be treated with A1200 mg day 1 of a 21-day cycle until disease progression, unacceptable toxicity or death. The kinetics of response to anti-PD1 therapy can be variable and in some cases characterized by pseudo-progression. In order to account for variable response kinetics to PD1 therapy, pts will be enrolled in 3 parallel cohorts based on best overall response (BOR) to PD1 therapy (stable disease; progressive disease; complete or partial response followed by progressive disease). The primary objective is BOR to A. Secondary endpoints include duration of response, progression free survival, overall survival, and safety. 37 pts will be enrolled per cohort. A Simon 2-stage design will be employed with a stopping rule for futility if 0 of the first 11 evaluable patients within a cohort have a confirmed objective response in Stage 1. A promising result would be if ≥3 responses are seen at the conclusion of stage 2. This design has 80% power to detect a true response rate of 15% in each cohort (null rate 2%; alpha 0.05). Mandatory biopsies at time of enrollment, archival tumor pre-PD1 directed therapy, and optional biopsy at the time of progression on A will be collected for exploratory studies of immune biomarkers of response and resistance. Clinical trial information: NCT03014648.
МЕТОДИЧЕСКИЕ ПОДХОДЫ К ОЦЕНКЕ ВОЕННО-ЭКОНОМИЧЕСКОГО ЭФФЕКТА В РЕЗУЛЬТАТЕ ВНЕДРЕНИЯ ТЕХНИЧЕСКИХ ИННОВАЦИЙ В СИСТЕМЕ МАТЕРИАЛЬНОГО ОБЕСПЕЧЕНИЯ ВОЙСК (СИЛ)
Authors: Boldyrev Oleg Alekseyevich , Kozin Mikhail Nikolayevich 
Published: September 2018

Задача обеспечения военной безопасности Российской Федерации в ситуации интенсивного геополитического давления и технологического превосходства государств, проводящих недружественную политику по отношению к нашей стране, ведет к необходимости технического переоснащения Вооруженных Сил Российской Федерации на основе инновационных технологий. Однако пока не разработаны методики оценки военно-экономического эффекта от применения технических инноваций в войсках, что может ухудшить качество принимаемых решений относительно целесообразности внедрения этих инноваций.Цель: разработка методики оценки военно-экономического эффекта от применения технических инноваций в системе материального обеспечения Вооруженных Сил Российской Федерации.Методы: общенаучные методы анализа и синтеза, метод экономико-математического моделирования.Результаты: выявлены факторы военно-экономического эффекта от применения технических инноваций в сфере материального обеспечения войск (сил) и построена методика его оценки.
ФОРМИРОВАНИЕ ПРОФЕССИОНАЛЬНОГО МИРОВОЗЗРЕНИЯ КУРСАНТОВ ВОЕННЫХ ВУЗОВ: ГУМАНИСТИЧЕСКИЙ И КУЛЬТУРНЫЙ АСПЕКТЫ
Authors: Tarasov Dmitry Yurievich 
Published: September 2018

Цель. В статье рассматривается проблема формирования мировоззрения военного специалиста, которая приобрела особую актуальность в условиях современного военного образования. Проводится теоретико-методологический анализ научных подходов, в рамках которых рассматривается обозначенная проблема. Предметом анализа выступают теоретические подходы к указанной проблеме, мыслителей и ученых разных исторических эпох. Авторы ставят своей целью раскрыть категории профессиональное мировоззрение офицера, гуманистические и культурные ценности.Метод или методология проведения работы. Основу исследования составляют классические методы теоретического ретроспективного анализа и синтезаРезультаты. Проведённый теоретический анализ позволил прийти к выводу о том, что профессиональное мировоззрение будущего офицера Росгвардии имеет свою специфику и представляет собой сложное системное образование включающее множество компонентов. Автор делает предположение о том, что одно из стратегических направлений развития системы образования в вузах войск национальной гвардии Российской Федерации видится в расширении информационного и культурного полей взаимодействия.Область применения результатов. Результаты исследования могут быть внедрены в образовательный процесс высшего военного профессионального образования.
PENGARUH CORPORATE SOCIAL RESPONSIBILITY TERHADAP PROFITABILITAS PERUSAHAAN GO PUBLIC YANG TERDAFTAR DI BURSA EFEK INDONESIA
Authors: Suryaningsih Nunuk , Ariesanti Alia 
Published: September 2018

Recent years many companies are increasingly recognizing the importance of implementing a program of corporat social resposibility (CSR) as part of ots business srategy. Intense competition in the business word sometimes makes the company justifies any means to increase profit with lower costs, thus resulting in corporate social responsibility aside. The study was conducted to provide empirical evidence of the influence of CSR on corporate profitability. This study used a sample of 20 companies listed on the Stock Exchange of manufacturing the 2005-2009 period. The research data obtained from annual financial reporting issued by the company each year. Determination of the sample using purposive sampling method. Testing the hypothesis using a simple linear regression analysis. The results show that the disclosure of CSR effect company profitability when viewed using the Return of Equity, but had no effect on Return on Assets and Return on Investment. In addition, the study provides empirical evidence that there are differences in the scope of the disclosure of Corporate Social Responsibility between in periods before and after the enactment of Law No.40 of 2007 regarding Limited Liability Company.