bluuebunny/crossref_metadata_2025 huggingface dataset:
Cabazitaxel with abiraterone versus abiraterone alone randomized trial for extensive disease following docetaxel: the CHAARTED 2 Trial: A trial of the ECOG-ACRIN Cancer Research Group (EA8153).
Authors: Kyriakopoulos Christos , Chen Yu-Hui , Duan Fenghai , Jeraj Robert , Luo Jun , Antonarakis Emmanuel S. , Liu Glenn , Carducci Michael Anthony
Published: May 2019

TPS5094

Background: The E3805 CHAARTED trial showed a significant survival benefit from early treatment with docetaxel in patients (pts) with high-volume metastatic hormone-sensitive prostate cancer (HSPC). However, eventually all these patient will develop castration-resistant disease (CRPC) and it is currently unknown what is the optimal treatment in that setting. We hypothesize that treatment with a second round of chemohormonal therapy –this time in the CRPC setting- will improve outcomes. Methods: This is a prospective randomized phase II open label trial led by ECOG-ACRIN. Pts (N = 210) with metastatic CRPC who have previously received docetaxel for HSPC will be randomized to 2 treatment arms (1:1): abiraterone/prednisone plus cabazitaxel for up to 6 cycles versus abiraterone/prednisone alone. Stratification factors include ECOG performance status, time from initiation of ADT to development of CRPC and visceral versus bone only metastases. The primary objective is to evaluate the efficacy of abiraterone/prednisone plus cabazitaxel versus abiraterone/prednisone alone. The primary endpoint of the trial is progression-free survival (PFS), defined clinically or radiographically. Secondary endpoints include PSA response, radiographic response, time to PSA progression, overall survival and safety. Exploratory objectives include response assessment based on AR-V7 status as well as by NaF PET/CT imaging. Key inclusion criteria include: metastatic CRPC, prior treatment with at least 3 cycles of docetaxel for metastatic HSPC, no prior treatment for CRPC (radium-223 or sipuleucel-T excluded), ECOG performance status of 0-2 and peripheral neuropathy of less than 2. The study was activated on 02/08/2018. As of 01/21/2019, 28/210 pts have been enrolled. Support: CA180820, CA180794, CA180799, CA180802; and Genzyme Corporation, a subsidiary of Sanofi S.A. Clinical trial information: NCT03419234.
A phase II Salvage Trial of AR Inhibition with ADT and Apalutamide with Radiation therapy followed by docetaxel in men with PSA recurrent prostate cancer (PC) after radical prostatectomy (STARTAR).
Authors: Zhang Tian , Koontz Bridget F. , Tagawa Scott T. , Nagar Himanshu , Bitting Rhonda L. , Frizzell Bart , Rasmussen Julia , Wilder Rhonda , Anand Monika , Winters Carolyn , Riggan Colleen , Lee Aileen , Healy Patrick , Wu Yuan , McNamara Megan Ann , Harrison Michael Roger , George Daniel J. , Armstrong Andrew J.
Published: May 2019

TPS5097

Background: Androgen deprivation combined with salvage external beam radiation therapy (RT) have improved survival for patients (pts) with non-metastatic hormone naïve PC and PSA recurrence after radical prostatectomy (RP). Our recent STREAM trial showed addition of enzalutamide to RT and ADT had a 3-year progression free survival (PFS) of 53%. Adding effective PC treatments in this setting may further improve 3-year PFS. Methods: STARTAR is an investigator-initiated phase 2 trial for salvage treatment of biochemically recurrent PC following prostatectomy. Key inclusion criteria include histologic prostate adenocarcinoma, either Gleason 7 with T3/positive margin/1-4 positive lymph nodes or Gleason 8-10 disease, PSA relapse within 4 years of prostatectomy (minimum PSA 0.2 ng/mL to maximum PSA 4 ng/mL). Treatment involves ADT with apalutamide for 9 months, continue with with prostate bed +/- nodal RT at month 3, followed by 6 cycles of docetaxel 75mg/m2 IV every 3 weeks for 6 cycles. The primary endpoint of the study is 3-year PFS. With a one-sided alpha of 0.05 to improve 3-year PFS from 50% to 75%, we will have 92% power by enrolling 42 pts (including 10% dropout rate) based on the binomial test. Key secondary endpoints include 1, 2, and 3-year PSA recurrence rates with testosterone recovery, PSA PFS, PSA nadir, time to testosterone recovery, and safety of combination therapy. Quality of life will be assessed by EPIC questionnaire. As of February 2019, we have enrolled and treated 12 pts in this PCCTC trial. Accrual to the STARTAR trial is ongoing (NCT03311555). Clinical trial information: NCT03311555.
Cognitive effects of androgen receptor (AR) directed therapies for advanced cancer of the prostate (COGCaP).
Authors: Van Julie , Penson David F. , Rademaker Alfred , Jackson James C. , Moses Kelvin A. , Morgans Alicia K.
Published: May 2019

TPS5098

Background: Androgen deprivation therapy (ADT) is the cornerstone of treatment for prostate cancer (CaP). However, the relationship between ADT and the development of cognitive dysfunction in men with CaP is controversial. Past studies had various methodological limitations, including the inconsistency and insensitivity of measures used for cognitive testing. Methods: COGCaP is a multi-site, prospective observational study of cognitive function and patient reported outcomes in men with CaP treated with ADT and androgen receptor (AR) directed therapies such as enzalutamide or abiraterone acetate (AA) conducted across four U.S. sites. Patients with metastatic castration-resistant or hormone sensitive CaP starting abiraterone (N=50), or non-metastatic or metastatic castration-resistant CaP starting enzalutamide (N=50) undergo cognitive and patient reported outcome assessments at baseline, 3, 6, and 12 months. The primary endpoint compares mean change in cognitive function between groups at 3 months using CANTAB, a computer-based measure of cognitive function. This design achieves a power of 80% to detect a between-group difference in mean cognitive composite score of < 1 standard deviation and a two-sided type I error rate of 0.05. Functional MRI (fMRI) images will be assessed between baseline and 3 months to assess structural and functional changes in the brain as secondary endpoints. Study patients will be incorporated into a model of genetic risk of cognitive dysfunction in order to identify populations that are especially vulnerable to cognitive change when undergoing androgen deprivation. This ongoing study will define a reproducible methodology for cognitive assessments via computer based tests that can be standardized and disseminated within multi-site trials of men with CaP. Clinical trial information: NCT03016741.
CALLA: Efficacy and safety of durvalumab with and following concurrent chemoradiotherapy (CCRT) versus CCRT alone in women with locally advanced cervical cancer: A phase III, randomized, double-blind, multicenter study.
Authors: Monk Bradley J. , Mayadev Jyoti , Nunes Ana T , Dabrowska Brown Alicja , Marcovitz Michelle , Lanasa Mark C.
Published: May 2019

TPS5597

Background: CCRT is the standard of care for locally advanced cervical cancer. CCRT with PD-1/PD-L1 pathway blockade may promote a more immunogenic environment through increased phagocytosis, cell death, and antigen presentation, leading to enhanced immune-mediated tumor surveillance. This Phase 3, randomized, multicenter, international, double-blind, placebo-controlled study is designed to determine the efficacy and safety of durvalumab with and following CCRT vs. CCRT alone in women with locally advanced cervical cancer (NCT03830866). Methods: The study will enroll immunotherapy-naïve adult patients (pts) with histologically confirmed cervical adenocarcinoma or cervical squamous or adenosquamous carcinoma (FIGO Stages IB2-IIB with node [N] positive and IIIA-IVA with any N) and no prior definitive surgical, radiation, or systemic therapy for cervical cancer. Approximately 714 pts will be randomized 1:1 to receive either durvalumab (1500 mg intravenously [IV]) or placebo every 4 weeks for 96 weeks. All pts will receive CCRT to the pelvis or pelvis + para-aortic radiotherapy field (45 Gy), followed by image-guided brachytherapy with cisplatin (40 mg/m2) IV or carboplatin (AUC2) IV once weekly for 5 weeks (6th dose optional). Randomization will be stratified by disease stage (FIGO Stage < III and N positive, FIGO Stage ≥III and N negative, or FIGO Stage ≥III and N positive) and region (US, Canada, EU, South Korea, and Japan vs. rest of the world). The primary endpoint is progression-free survival (assessed by investigator per RECIST v1.1 or histopathologic confirmation of local tumor progression). Secondary endpoints are overall survival, objective response and complete response (CR) rates, duration of response in pts with CR, incidence of local or distant disease progression or secondary malignancy, disease-related symptoms, and health-related quality of life (EORTC QLQ-C30 and EORTC QLQ-CX24). Pharmacokinetics, immunogenicity, and safety of durvalumab will also be assessed. Pt enrollment is ongoing. Clinical trial information: NCT03830866.
AGO-OVAR 2.29 (ENGOT-ov34): Atezolizumab in combination with bevacizumab and chemotherapy versus bevacizumab and chemotherapy in recurrent ovarian cancer (ROC).
Authors: Marme Frederik , Pautier Patricia , Van Nieuwenhuysen Els , Reuss Alexander , Redondo Andres , Lindemann Kristina , Kurzeder Christian , Marth Christian , Burges Alexander , Pietzner Klaus , Wimberger Pauline , De Gregorio Nikolaus , Harter Philipp
Published: May 2019

TPS5601

Background: A standard non-platinum based treatment option in patients with relapsed ovarian cancer is bevacizumab in combination with paclitaxel or pegylated liposomal doxorubicin, but responses are still short-lived. Checkpoint-inhibitors as single agent have limited activity in ovarian cancer. However, the role of the checkpoint-inhibitor like atezolizumab, in addition to chemotherapy and bevacizumab in ovarian cancer is so far undefined. Methods: AGO-OVAR 2.29 is a randomized (1:1), double blinded, phase III trial evaluating the efficacy and safety of atezolizumab plus bevacizumab and chemotherapy (weekly paclitaxel or pegylated liposomal doxorubicin) compared with placebo plus bevacizumab and chemotherapy in patients with recurrent ovarian-, fallopian tube, or primary peritoneal cancer with 1st or 2nd relapse within 6 months after platinum-based chemotherapy or 3rd relapse. A tumor biopsy available at study entry for PD-L1 testing is mandatory. Patients are treated with chemotherapy plus bevacizumab +/- atezolizumab/placebo until progression or prohibitive toxicity. Co-primary endpoints are overall survival and progression-free survival. It is planned to randomize 664 patients. A safety interim analysis will be done when 24 patients have been randomized and completed at least cycle 1. As of 1st February 2019, 24 patients have been randomized. Clinical trial information: NCT03353831.
Phase Ib clinical investigation of intraperitoneal ipilimumab and nivolumab in patients with peritoneal carcinomatosis due to gynecologic malignancy.
Authors: Hinchcliff Emily , Peng Weiyi , Bayer Virginia , Haymaker Cara L. , Huang Steven Y , Sheth Rahul , Westin Shannon Neville , Lu Karen H. , Hwu Patrick , Jazaeri Amir A.
Published: May 2019

TPS5606

Background: The peritoneal cavity is a frequent site of metastasis and recurrence for gynecologic malignancy, including approximately 80% of epithelial ovarian cancer (EOC) that presents with peritoneal involvement. These observations have led to the use of intraperitoneal (IP) route of administration for traditional cytotoxic chemotherapy. IP immunotherapy is a recognized but under explored area of clinical investigation with many potential advantages. Indeed, IP administered antibodies in both animals and human subjects are associated with absent or much lower peripheral blood concentrations. In addition to higher local and lower systemic exposure, other theoretical advantages include preferential binding to intraperitoneal and intratumoral immune cells, and absorption through the draining lymphatics of the peritoneal cavity. These pelvic and peri-aortic lymph nodes represent the most relevant lymphoid organs and as such may be the ideal site for T cell activation and trafficking back to the peritoneal tumor. Methods: The trial (NCT03508570) is a single-institution phase Ib trial to determine the recommended phase II dosing (RP2D) of IP administration of nivolumab in combination with ipilimumab. For the purpose of dose finding, the assessment period for dose limiting toxicity (DLT) is 12 weeks. The trial starts with a safety lead-in to confirm the safety of IP nivolumab before combining it with ipilimumab. A maximum sample size of 12 will be used to find the RP2D for nivolumab, up to 24 patients for the combination, and a planned expansion will be carried out such that at least 12 EOC patients are treated at RP2D of the intraperitoneal combination strategy. The secondary objectives are to describe the pharmacokinetics and toxicities, and to estimate the clinical benefit rate for the expansion cohort. Translational objectives include description of immunologic and biologic changes in serial blood and IP fluid collections as well as pre and on-treatment biopsies. Eligibility criteria include recurrent or progressive biopsy-confirmed platinum resistant EOC or other gynecologic cancer with measurable peritoneal disease, and no exposure to prior treatment with checkpoint inhibition. Enrollment began in January of 2019 with 3 subjects enrolled to date. Accrual update will be provided at the annual meeting. Clinical trial information: NCT03508570.
KEYNOTE-689: Phase 3 study of adjuvant and neoadjuvant pembrolizumab combined with standard of care (SOC) in patients with resectable, locally advanced head and neck squamous cell carcinoma.
Authors: Uppaluri Ravindra , Lee Nancy Y. , Westra William , Cohen Ezra E.W. , Haddad Robert I. , Temam Stephane , Le Tourneau Christophe , Chernock Rebecca , Safina Sufia , Klochikhin Arkadiy , Meirovitz Amichay , Braña Irene , Ge Joy Yang , Swaby Ramona F. , Bidadi Behzad , Adkins Douglas
Published: May 2019

TPS6090

Background: Evidence of efficacy and pathological response at the time of surgery was reported in two phase 2 studies (NCT02296684 and NCT02641093) of preoperative pembrolizumab in patients with high-risk, resectable, locally advanced (LA) head and neck squamous cell carcinoma (HNSCC). The randomized, open-label, phase 3 KEYNOTE-689 trial ( NCT03765918) will evaluate efficacy and safety of pembrolizumab as neoadjuvant and adjuvant therapy in combination with SOC (radiotherapy ± cisplatin) in patients with previously untreated, resectable LA HNSCC. Methods: Patients with newly diagnosed LA HNSCC will be randomly assigned 1:1 to two treatment arms. Patients in arm A will receive neoadjuvant pembrolizumab (200 mg Q3W for two cycles) followed by surgical resection then SOC plus adjuvant pembrolizumab (15 cycles). Patients in arm B will undergo only surgical resection followed by adjuvant SOC. Eligibility criteria will include age ≥18 years; newly diagnosed, resectable, stage III/IVA HNSCC (AJCC Cancer Staging Manual, 8th edition); and ECOG performance status 0-1. Randomization will be stratified by primary tumor site (oropharynx/oral cavity vs larynx vs hypopharynx), tumor stage (III vs IVA), and HPV p16 status (oropharynx p16 positive vs oropharynx p16 negative or larynx/hypopharynx/oral cavity). Treatment will continue until disease progression, unacceptable toxicity, or decision to withdraw. Patients in arm A will undergo the first radiologic imaging assessment after two cycles of neoadjuvant pembrolizumab and before surgery. In both arms, postoperative imaging will be performed 12 weeks after SOC, then every 3 months until the end of year 3, and then every 6 months until the end of year 5. Dual primary end points are major pathological response, defined as ≤10% invasive squamous cell carcinoma within resected primary tumor and sampled regional lymph nodes per blinded central pathology, and event-free survival. Secondary end points include overall survival, pathological complete response, and safety and tolerability. Recruitment is ongoing and will continue until ~600 patients are enrolled. Clinical trial information: NCT03765918.
Comparative effectiveness trial of transoral head and neck surgery followed by adjuvant radio(chemo)therapy versus primary radiochemotherapy for oropharyngeal cancer (TopROC).
Authors: Busch Chia-Jung , Laban Simon , Wittekindt Claus , Stromberger Carmen , Tribius Silke , Betz Christian Stephan , Klußmann Jens Peter , Budach Volker , Muenscher Adrian
Published: May 2019

TPS6093

Background: For locally advanced, transorally resectable oropharyngeal cancer (OPSCC), both, surgical resection and risk-adapted adjuvant (chemo)radiotherapy or definite chemoradiotherapy with or without salvage surgery are considered the current standard of care. To date, these two different therapeutic approaches for transorally resectable OPSCC have not been compared head to head in a randomized trial yet. The goal of this study is to compare primary transoral surgery followed by adjuvant treatment with definitive chemoradiation for resectable OPSCC, especially with regards to loco-regional control as well as organ function. Methods: TopROC is a prospective, two-arm, open label, multicenter, randomized controlled comparative effectiveness study. Eligible pts. are ≥18 years old with treatment-naïve, histologically proven OPSCC (T1, N2a-c, M0; T2, N1-2c, M0; T3, N0-2c, M0 TNM 7th ed.) which are amenable to transoral resection, ECOG PS ≤2 and no distant metastasis. p16 immunohistochemistry by local pathology or FFPE tissue must be available for central diagnostic. 280 pts. will be randomly assigned (1:1) to surgical treatment (arm A) or chemoradiation (arm B). Standard of care treatment will be done according to daily clinical practice. Arm A consists of transoral surgical resection with neck dissection followed by risk-adapted adjuvant (chemo)radiation. Pts. treated in arm B receive standard chemoradiation, residual tumor may be subject to salvage surgery. Follow-up visits are planned until three years after treatment. Primary endpoint is time to local or locoregional failure or death from any cause (LRF). Secondary endpoints include overall and disease-free survival, toxicity, patient reported outcomes and cost-effectiveness analysis. Approximately 20 centers will be involved in Germany. This trial is supported by the German Cancer Aid and accompanied by a large scientific support program. Recruitment started in January 2018. Clinical trial information: NCT03691441.
Roman: Reduction in oral mucositis with avasopasem manganese (GC4419)—Phase 3 trial in patients receiving chemoradiotherapy for locally-advanced, non-metastatic head and neck cancer.
Authors: Holmlund Jon , Brill Jeffrey Mark , Lee Christopher M. , Saunders Deborah , Sonis Stephen T. , Downs Matt , Anderson Carryn M.
Published: May 2019

TPS6096

Background: Approximately 70% of patients receiving intensity-modulated radiotherapy (IMRT) plus cisplatin for locally advanced head and neck cancer (HNC) develop SOM, defined as WHO Grade 3 or 4, which limits patients' ability to eat solids (Gr 3) or liquids (Gr 4, requiring enteral nutrition). An RT-induced burst of superoxide initiates oral mucositis (OM) development. GC4419, a superoxide dismutase mimetic, interrupts this process by converting superoxide to H2O2. It showed promising reduction of SOM in a published open-label Phase 1b/2a trial (IJROBP 1 Feb 2018). In a subsequent randomized, double-blind placebo-controlled trial in 223 patients receiving IMRT/cisplatin for HNC (ASCO 2018), 90 mg of GC4419 administered M-F prior to IMRT demonstrated statistically significant reduction in SOM duration (p=0.024, median 1.5 days @ 90 mg vs 19 days placebo) and meaningful reductions @ 90 mg in SOM incidence (43% vs 65%) and severity (incidence of Grade 4, 16% vs 30%). The safety profile was acceptable and consistent with the known toxicities of IMRT/cisplatin. Methods: 335 patients at multiple centers in the U.S. and Canada with locally-advanced, nonmetastatic head and neck cancer (oral cavity/oropharyngeal) receiving 70 Gy IMRT (>50 Gy to > 2 oral sites) plus cisplatin (40 mg/m2 qwk x 6-7, or 100 mg/m2 q3wk x 3) are being randomized (double-blinded) 3:2 to 90 mg of GC4419 or placebo, M-F before each RT fraction. Enrollment is stratified by cisplatin schedule and treatment setting (definitive vs post-op). OM by the WHO scale will be assessed twice weekly during RT & weekly for 2 weeks post RT. The primary efficacy endpoint is incidence of SOM through the end of IMRT. Secondary efficacy endpoints include severity (incidence of Grade 4 OM through the end of IMRT), & days of SOM (days from first to last SOM for all patients, with patients never developing SOM having 0 days of SOM by definition). Days of SOM for the subset developing SOM will be analyzed descriptively. Patients will be followed for one year post IMRT for tumor progression/recurrence and for two years for survival. Supported by Galera Therapeutics, Inc. Clinical trial information: NCT03689712.
Patient related outcomes in cancer patients in Croatia.
Authors: Trivanovic Dragan , Hrstic Irena , Budisavljevic Anuska , Kopic Boris , Nincevic Bruno
Published: May 2019

TPS6650

Background: Accurate evaluation of symptom intensities is essential for optimal cancer care and improving the quality of life of patients. An inappropriate interpretation of symptoms may lead to treatment outcomes failure, overdose of medication, or may leave the patients undertreated. However, the perception of symptoms can vary between the treating physician and patient. Physicians appear to underestimate the patient symptoms. And this variation in the perception of side effects can lead to wrong assumptions and subsequent treatment changes, affecting treatment effectiveness and quality of life. There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, leaving open the question of whether the benefits of systems to reveal self-reports outweigh their added cost. There are several tools for assessment of symptoms in oncology. In cancer treatment clinical trials, the standard source of adverse symptom data is clinician reporting by use of items from PRO-CTCAE, developed by NCI. To address these questions, we conducted a single-center prospective trial to test whether systematic tablet computer-based collection of patient-reported symptoms during chemotherapy treatment, with automated alerts to clinicians for severe adverse events (grade 3-4) will change in questionnaire score at 6 months compared with baseline. Secondary endpoints will include difference in unscheduled clinic visits frequency, and survival. Methods: Patients initiating chemotherapy at General Hospital Pula Oncology Clinic for advanced or metastatic gastrointestinal, lung, breast, genitourinary, or gynecologic cancers will be enrolled in a nonblinded, prospective trial of self-reporting of symptoms, compare with usual care. Patients receiving chemotherapy and their clinicians will be independently asked on the same day to complete 10 symptoms (including fatigue, pain, nausea, vomiting, diarrhea, dysgeusia, appetite, sleep disturbance, fever and hair loss). Participants will remain on study until discontinuation of cancer treatment, withdrawal, or death. All participants will provide written informed consent and followed for up to 28 months or until death. To compare how patient’s vs clinician’s reports relate to clinical events, a time-dependent Cox regression model adjusted for covariates including cancer type, age, sex, and education level will be used to measure associations between reaching particular grade severity thresholds with the risk of death and unscheduled clinic visits. Clinical trial information: 2019-000855-15.
Pembrolizumab versus placebo as adjuvant therapy in resected high-risk stage II melanoma: Phase 3 KEYNOTE-716 study.
Authors: Carlino Matteo S. , Ascierto Paolo Antonio , Eggermont Alexander M. , Gershenwald Jeffrey E. , Grob Jean Jacques , Hauschild Axel , Kirkwood John M. , Long Georgina V. , Mohr Peter , Robert Caroline , Ross Merrick I. , Scolyer Richard A. , Sondak Vernon K. , Yoon Charles , Poklepovic Andrew Stewart , Rutkowski Piotr , Anderson James R. , Ahsan Sama , Ibrahim Nageatte , Luke Jason J.
Published: May 2019

TPS9596

Background: Adjuvant pembrolizumab showed significantly longer recurrence-free survival than placebo in patients with resected stage III melanoma in the KEYNOTE-054 study. KEYNOTE-716 (NCT03553836) is a randomized, placebo-controlled, double-blind, multicenter phase 3 study of adjuvant pembrolizumab in patients with surgically resected high-risk stage II melanoma. Methods: Key eligibility criteria are age ≥12 y with newly diagnosed, completely resected stage IIB/IIC cutaneous melanoma, defined by the AJCC Cancer Staging Manual, 8th edition (wide excision and negative sentinel lymph node biopsy with no evidence of distant metastasis). Patients with mucosal or uveal melanoma or prior treatment (including radiation) for melanoma beyond resection of primary disease within 12 wk of the start of study treatment were excluded. In this 2-part study, in the double-blind phase (part 1), patients will be randomly assigned 1:1 to receive pembrolizumab 200 mg for patients ≥18 y or 2 mg/kg for patients ≥12 y to < 18 y (maximum dose, 200 mg) or placebo every 3 wk for 17 cycles. Study treatment will begin within 12 wk of complete resection. Tumor imaging will be performed every 24 wk while treatment is ongoing, at the end of treatment, every 6 mo for the first 3 y off treatment, and then yearly for up to 2 y or until recurrence (up to 5 y of total imaging). Adverse events will be recorded until 30 d after treatment end (90 d for serious AEs) and graded per National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. In the unblinded phase (part 2), patients with confirmed recurrence may be rechallenged (patients received pembrolizumab in part 1) or crossed over to pembrolizumab (patients received placebo in part 1). Resected local or distant recurrence or unresectable disease will be treated for an additional 17 or 35 cycles, respectively. Tumor imaging in part 2 will occur every 12 wk during treatment. The primary end point is recurrence-free survival; secondary end points are distant metastasis-free survival, overall survival, and safety. Approximately 954 patients will be enrolled. Clinical trial information: NCT03553836.
Pilot integrated biomarker study of VX15/2503 in combination with ipilimumab and/or nivolumab in patients with resectable metastatic melanoma.
Authors: Lowe Michael C. , Lesinski Gregory B. , Delman Keith A. , Yushak Melinda Lynne , Evans Elizabeth E. , Fisher Terrence Lee , Kudchadkar Ragini Reiney
Published: May 2019

TPS9603

Background: Interrogation of the tumor microenvironment (TME) is crucial to provide insight into biological activity, resistance mechanisms and implementation of rational combination immunotherapies. Semaphorin 4D (SEMA4D, CD100) has broad immunomodulatory effects in the TME. In preclinical models, blockade of SEMA4D promoted immune infiltration and reduced recruitment of immunosuppressive myeloid cells. Preclinical combinations of anti-SEMA4D with immune checkpoint inhibitors (ICIs) enhanced T cell activity and tumor regression. VX15/2503 (pepinemab), an IgG4 humanized monoclonal antibody targeting SEMA4D, is being evaluated in an integrated biomarker trial to characterize immunomodulatory effects in melanoma (NCT03769155). Methods: Patients with biopsy-proven stage IIIB, C, and D melanoma are eligible. Prior to curative-intent surgery, patients receive pepinemab alone or in combination with nivolumab and/or ipilimumab every three weeks for two doses. A control cohort proceed directly to surgery. Resection specimens will be collected for comparison across treatment groups and with a pre-treatment biopsy. Blood will be collected for PK, PD, and correlative biomarker assessments. The primary objective is to evaluate effects on the immune profile in TME and peripheral blood. Additional objectives include safety of pepinemab (alone and in combination with ICI), and pathologic and radiographic responses. Multiplex flow cytometry panels were created to phenotype cells in the TME and periphery. A multiplex IHC assay utilizing a sequential probe and strip procedure has been qualified that allows co-localization, orientation, and quantification of multiple immune markers. Analysis of immune subsets include cytotoxic T cells, neutrophils, Tregs, DCs, monocytes, macrophages, and myeloid-derived suppressor cells. Target engagement and expression of SEMA4D and its receptors will be evaluated. As of 01 Feb 2019, 8 of 36 patients have been enrolled. This trial will provide the first biomarker-driven clinical assessment of anti-SEMA4D antibody activity to reprogram the TME. Clinical trial information: NCT03769155.
Efficacy and Usability of a Novel Barrier Device for Preventing Injection Port Contamination: A Pilot Simulation Study
Authors: Wax David B. , Shah Anjan , Shah Ronak , Lin Hung-Mo , Katz Daniel
Published: May 2019

Contamination of intravenous (IV) ports and stopcocks has been associated with postoperative infections. We tested the usability and efficacy of a novel passive shielding device to prevent such contamination even in the absence of hand hygiene or port disinfection. In a desktop setting with deliberately contaminated hands, qualitative port contamination was detected after 5/60 (8.3%; 95% confidence interval [CI], 2.8–18.4) control port injections versus 0/60 (0%; 95% CI, 0–6.0) shielded injections (P = .025). In clinical simulations with a quantitative bioburden assay (measured in relative light units [RLUs]), median (interquartile range [IQR]) postsimulation bioburden was 46 (32–53) vs 27 (21–42) RLU for the control versus intervention groups (P = .036), yielding a median shift of −13 RLU (95% CI, −2 to −26) in favor of the shielding. Usability of the device was acceptable to practitioners.
Concorrência no mercado portuário de contêineres
Authors: Moreira Egon Bockmann
Published: May 2019

.
Infração à ordem econômica pela Uber
Authors: Maia Conselheiro Mauricio Oscar Bandeira
Published: May 2019

.
An Epistemic Interpretation of Paraconsistent Weak Kleene Logic
Authors: Szmuc Damian E.
Published: May 2019

This paper extends Fitting’s epistemic interpretation of some Kleene logics to also account for Paraconsistent Weak Kleene logic. To achieve this goal, a dualization of Fitting’s “cut-down” operator is discussed, leading to the definition of a “track-down” operator later used to represent the idea that no consistent opinion can arise from a set including an inconsistent opinion. It is shown that, if some reasonable assumptions are made, the truth-functions of Paraconsistent Weak Kleene coincide with certain operations defined in this track-down fashion. Finally, further reflections on conjunction and disjunction in the weak Kleene logics accompany this paper, particularly concerning their relation with containment logics. These considerations motivate a special approach to defining sound and complete Gentzen-style sequent calculi for some of their four-valued generalizations.
A SÍNDROME DE BURNOUT E O TRABALHO DE TÉCNICOS DE ENFERMAGEM EM UM HOSPITAL PRIVADO
Authors: Sousa Caissa Veloso e , Cabral Janaína Michelle Santos , Batista Nayara Kelly
Published: May 2019

Este estudo objetivou analisar como se encontram configuradas as variáveis da Síndrome de Burnout em técnicos de enfermagem de um hospital privado localizado na cidade de Belo Horizonte - MG. A abordagem teórica ancorou-se em aspectos relacionados à influência do trabalho na vida do ser humano e suas consequências para o indivíduo, como o estresse e a Síndrome de Burnout. Em termos metodológicos, a pesquisa foi descritiva, de abordagem qualitativa. Foram entrevistados 10 técnicos em enfermagem de um hospital privado. Os resultados demonstraram o desgaste emocional enfrentado por estes profissionais, como também o sentimento de querer abandonar a profissão. A família foi utilizada como uma estratégia no combate ao sofrimento e, a despersonalização, uma das variáveis que caracteriza a síndrome, se mostrou reduzida em relação aos profissionais estudados.
INOVAÇÃO EM SERVIÇO ORIENTADA PARA GESTÃO DE RESÍDUOS: ESTUDO DE CASO EM UMA PRESTADORA DE SERVIÇOS NA REGIÃO METROPOLITANA DE BELO HORIZONTE
Authors: Alves Eder Junior , Gonçalves Carlos Alberto
Published: May 2019

É consabido que a Construção Civil provoca externalidades de grande monta no ambiente. Este artigo contribui para a área da Responsabilidade Social Corporativa (RSC) em organizações, buscando inovações que reduzam os impactos provocados por resíduos da Construção Civil na sociedade. O objetivo deste artigo é analisar a estruturação empresarial e melhores práticas em uma organização de pequeno porte que oferece inovação em serviço, orientada para gestão de resíduos, possibilitando descobrir quais melhorias podem ser implementadas neste processo evolutivo. Trata-se de um estudo de caso que teve as entrevistas participativas e a análise documental como instrumentos habilitadores. A organização escolhida conquistou prêmios devido a sua oferta de serviços inovadores que apoiam a gestão de resíduos da Construção Civil. Os resultados foram analisados sob a perspectiva da inovação, da RSC e da teoria dos stakeholders. Conclui-se que uma organização inova quando busca continuar agregando valor, transformando constrangimento ambiental em novos negócios. Pode-se alcançar melhores práticas em gestão dos resíduos por meio do conhecimento e das lições aprendidas e desenvolvidas por meio de um repositório que coleta, armazena e distribui informações sobre experiências em projetos. Por fim, é possível melhorar a confecção dos contratos, disponibilizando-os para consultas pelas partes interessadas e possibilitando melhor controle das tarefas.
NA TRILHA DA SUSTENTABILIDADE: O CASO DA DENTAL JR.
Authors: Kieling Ana Paula , Leripio Alexandre De Avila
Published: May 2019

O presente caso para ensino tem como objetivo oportunizar aos alunos a vivência de situações no contexto de sustentabilidade nos negócios por intermédio da Clínica Odontológica Dental Jr., proporcionando conhecimentos sobre gestão de saúde, gestão sustentável e gerenciamento de aspectos e impactos ambientais. A Dental Jr. é uma clínica odontológica localizada no centro de Florianópolis – SC, gerenciada por Fabiano Rodrigues, Cirurgião Dentista e Administrador por formação. Em 2016, com boa rentabilidade e uma carteira de pacientes considerável, a empresa busca crescimento por meio de uma gestão mais sustentável e, para tal, contrata uma consultora, Cristina Matos, para apoiá-la na solução de um dilema: como definir estratégias sustentáveis para a melhoria de seus processos. Como instrumento de ensino, o caso foi desenvolvido para uso em cursos de Graduação e Pós-Graduação em Administração, Gestão Ambiental e Gestão de Saúde, quando do debate de temas como gestão ambiental e sustentabilidade em disciplinas como Sustentabilidade das Organizações, Gestão Ambiental e Gestão de Saúde.
A PERCEPÇÃO DE UM CUIDADOR A RESPEITO DA QUALIDADE DE VIDA DO IDOSO COM ALZHEIMER: RELATO DE EXPERIÊNCIA DO PROJETO TEORIAS E PERSPECTIVAS EM ENVELHECIMENTO HUMANO
Authors: COSTA André Felipe da , SILVA Ana Maria Costa da , VICENTE Aline Janete , ALMEIDA Mayara de Paula , BOSSARDI Carina Nunes
Published: May 2019

O presente estudo faz parte de um projeto desenvolvido durante umadisciplina da graduação em Psicologia. Para se discutir a respeito das perspectivas em envelhecimento humano, objetivou-se conhecer a percepção de um cuidador sobre a qualidade de vida do idoso com Alzheimer, com base em suas expectativas, experiências e ações em relação a essa situação. Esta pesquisa é de caráter qualitativo, com a qual foi realizado um estudo de caso de um cuidador. Como método foram utilizadas uma entrevista semiestruturada e a análise de conteúdo de Bardin. Com base na autopercepção desse cuidador, nota-se a importância da espiritualidade, remédios, profissionais e de Políticas Públicas para a manutenção da qualidade de vida de ambos, sendo que esta évista, em geral, como positiva, mas cheia de desafios devido à mudança que a relação que o cuidador e o idoso sofrem no decorrer do tempo. A discussão dos dados foi baseada na Teoria do Curso de Vida de Paul Baltes, perspectiva expressiva na compreensão dos processos de desenvolvimento e de envelhecimento humano. Os resultados salientam a necessidade de novas pesquisas a respeito do tema e indicam a importância de discussões desde as salas de aula, voltadas à realidade da população. Espera-se que esse estudo tenha implicações na formação dos profissionais de graduação, tendo em vista possibilidades de interverção visando à promoção de saúde dos idosos e de seus cuidadores.
PERCEPÇÃO DA EQUIPE TÉCNICA SOBRE AS PRÁTICAS CORPORAIS NA REDUÇÃO DE DANOS EM DEPENDENTES QUÍMICOS
Authors: MANSKE George Saliba , ONISHI Luiz Antonio
Published: May 2019

Esta pesquisa teve como objetivo compreender a percepção da equipe técnicade um Centro de Atenção Psicossocial (CAPS-ad) num município do sul do Brasil sobre as influências das práticas corporais na redução de danos nos dependentes químicos. Os dados foram coletados por meio de uma entrevista semiestruturada, sendo analisados sob a ótica da análise temática. Os resultados da pesquisa demonstram que a equipe técnica possui conhecimento sobre as práticas corporais e, mesmo não conhecendo todo o universo desta atividade, acredita que deveria fazer parte do rol de opções a serem ofertadas quando da estruturação dos Projetos Terapêuticos Singulares (PTS).
RACIONALIZAÇÃO DAS AÇÕES DE CONTROLE INTERNO E AUDITORIA COMO PROCESSO DE CONTROLE NA GESTÃO DA SAÚDE EM UNIDADES HOSPITALARES NO CONTEXTO BRASILEIRO
Authors: GUERINI Isabelle Christine , GUERINI Eduardo
Published: May 2019

O presente artigo tem como objetivo descrever sucintamente a racionalizaçãodas ações de controle interno e auditoria nas gerências das unidades hospitalares no contexto brasileiro. A necessidade de mecanismos de gestão com implantação de auditagem derivou da necessidade de controles internos para melhoria contínua na gestão hospitalar, como resultado de um processo derivado da universalização proposta na regulação jurídica, garantindo a universalização do acesso, destacando uma clara orientação para estabelecimento de metas quantitativas e qualitativas. Elaborou-se brevehistórico da implantação e da implementação de práticas gerenciais no sistema de saúde brasileiro, a racionalização, resultante de políticas públicas que são monitoradas por padrões de desempenho com resultados vinculados ao planejamento e cumprimento de metas almejadas. Neste sentido, observou-se que, no sistema de saúde pública ou privada, as variadas formas de organização hospitalar têm como claro resultado a transparência dos processos – elementos preponderantes para efetivação da prática de auditagem interna e externa nas unidades hospitalares no contexto brasileiro.
DESAFIO ÉTICO NA COMUNICAÇÃO DE HISTÓRIAS DE VIDAS COM ESCLEROSE SOBRE ÉTICA MÚLTIPLA
Authors: VENERA Raquel Alvarenga Sena , BRUNKEN Pedro Antônio Testoni , GOMES Jessica Fernanda , VENERA José Isaías
Published: May 2019

Este artigo traz reflexões teóricas construídas no Grupo de PesquisaSubjetividades e (auto)biografias. Trata-se de duas pesquisas de iniciação científica e inovação que desenvolveram produtos diferentes para comunicar Histórias de Vidas de pessoas diagnosticadas com Esclerose Múltipla. Ambas dialogaram de forma interdisciplinar com a Comunicação, especialmente com a ética no Jornalismo, a História e o Patrimônio Cultural, mas, sobretudo, estiveram atentas à questão ética das pesquisas (auto)biográficas. Com o foco na ética e nas epistemologias que nortearam decisões para as edições dessas histórias, a questão “O que fazer com a palavra do outro?” (ARFUCH,2010) foi a pergunta que perseguiu o trabalho. A exploração do trauma em uma mídia, ou a espetacularização da ‘superação’, ou ainda a sensibilidade para a conscientização da doença foram decisões conscientes do trabalho de comunicação e nessas pesquisas funcionaram como caminho reflexivo para pensar os campos envolvidos.
Evaluation of groundwater supply potential from hydraulic parameters estimated from vertical electrical sounding (VES) in Ikeduru, south east Nigeria
Authors: Jacinta Chiemela Nwosu , I Nwosu Leonard , O Chukwu Godwin
Published: May 2019

A Vertical Electrical resistivity Sounding (VES) survey was carried out, to study the groundwater supply potential, protective capacity and soil corrosivity of aquifers in Ikeduru Local Government Area of Imo state, Nigeria. A total of ten (10) geoelectric soundings were acquired. Schlumberger electrode configuration was used in acquiring the data. Six to seven geoelectric layers were delineated from the interpreted results, the Aquifers were delineated between the fifth and sixth geoelectric layers, having an apparent resistivity above 1000Ωm, with the highest thick of 69.0m at a depth of 144.0m. Longitudinal Conductance, Hydraulic Conductivity, Transmissivity and Product Conductance range are as followings for the aquifers; 1.720 – 127.000 x 10-3Ω-1, 15.90 – 188.79m/day, 1093.3 – 1097.1m2/day and 2.590 – 252.50 x 10-3 respectively. Inferring from our hydraulic parameters, all the aquiferous zones have very high designation, wwithdrawal of great regional importance of groundwater supply potential and practically noncorrosive, soil corrosivity. 40% percentage of the aquiferous units have very good protective capacity, while for excellent and good protective capacity of the study are is 30%. All the VES points are said to be a very viable potential for safe source for groundwater exploration.
Major structural elements and petrophysical properties of the miocene section, â€œXYZ Fieldâ€, western shallow Offshore Depobelt, Niger Delta
Authors: M.A Ajibade , Adekola Ajibade , Olowokere M.T.
Published: May 2019

R1, R2, R3, and F. reservoir units were identified in the XYZ Field. The reservoirs are within the Oil proven fault block and F reservoir is located on the footwall structure of the second synthetic fault with similar structural characteristics. The faulting in the XYZ field resulted in a downward movement of the XYZ Discovery relative to the XYZ prospects. The structural development process of the field was a syn-sedimentary. This explains why the XYZ-1 penetration in the footwall of the synthetic found oil-in F sand. However, petrophysical results show that the reservoirs of interests have good petrophysical properties with minimum porosity of 0.1 and maximum water saturation of 0.7. The discoveries by the XYZ-1 well prove the existence of a working hydrocarbon source and charge system. However the distribution pattern of the discovered hydrocarbons is not yet understood.Â Â
Efek Pemberian Midazolam atau Propofol Terhadap Lama Penggunaan Ventilator Mekanik di ICU RSUP Dr. Kariadi
Authors: Nugroho Rio Kristian , Aisyahani Aisyahani , Leksana Ery , Pujo Jati Listiyanto
Published: May 2019

Pendahuluan : Sedasi di ruang intensif dapat memperbaiki outcome perawatan dan membuat pasien lebih nyaman, namun juga berpotensi memperpanjang durasi ventilasi mekanik dan length of stay (LOS). Obat yang saat ini sering digunakan adalah midazolam, namun durasi kerja midazolam dapat memanjang pada pasien dengan gagal fungsi organ. Propofol adalah obat sedasi dengan klirens tinggi dan tanpa metabolit aktif yang dapat digunakan untuk memperpendek durasi ventilasi mekanik dan LOS pasien. Membandingkan durasi ventilasi mekanik dan biaya sedasi pada pasien pascabedah di ruang intensif yang disedasi menggunakan midazolam dan propofol.Metode : Dilakukan penelitian obser vasional dengan desain cross-sectional terhadap 30 pasien pascabedah dengan ventilator di ICU yang dibagi menjadi 2 kelompok secara acak, masing-masing kelompok terdiri dari 15 pasien. Kelompok I mendapat midazolam bolus 0,02-0,08 mg/kg IV, dilanjutkan infus kontinyu dosis 0,04-0,2 mg/kg/jam. Kelompok II mendapat Propofol bolus 1,5-2,5 mg/kg IV, dilanjutkan infus kontinyu dosis 5-80 μg/kg/menit. Target skor RASS adalah -1 sampai -2, yang dipantau 1 jam pascasedasi, dilanjutkan tiap 4 jam setelahnya. Pencatatan dilakukan terhadap durasi ventilator mekanik, rerata skor RASS, dan biaya sedasi.Hasil : Penelitian ini menunjukan bahwa dur asi ventilasi mekanik dan biaya sedasi pada kelompok propofol lebih rendah daripada midazolam, namun perbedaannya tidak bermakna dengan nilai p≤0,05.Kesimpulan : Sedasi pasien pascabedah dengan ventilator di r uang intensif dengan propofol lebih efektif dalam mengurangi durasi ventilasi mekanik dan biaya sedasi daripada midazolam, namun tidak berbeda bermakna.
Kateter Epidural Terputus Saat Dipasang
Authors: Hadiyanto M Faizal , Sutiyono Doso
Published: May 2019

Latar belakang: Anestesia epidural adalah satu bentuk dari anestesia regional dan merupakan salah satu bentuk teknik blok neuroaksial, dimana penggunaannya lebih luas daripada anesthesia spinal. Teknik epidural sangat luas penggunaanya pada anestesia operatif, analgesia untuk kasus obstetri, analgesia post operatif dan untuk nyeri kronis. Morbiditas dan bahkan mortalitas pascaoperasi dapat dikurangi ketika blokade neuraksial digunakan, baik sebagai agen tunggal maupun sebagai kombinasi dengan anestesi umum. Kasus: Seorang wanita usia 45th, ASA II dengan Adenokarsinoma Lambung yang akan menjalani operasi Gastrektomi Parsial. Penilaian preoperasi pasien sudah dalam kondisi yang optimal. Direncanakan akan dilakukan anestesi dengan teknik Epidural, insersi pada ruang intervertebra lumbal 3-4 dengan pemasangan kateter epidural tetapi gagal dipasang dan terputus 1cm saat pencabutan. Kemudian teknik anestesi dikonversi menjadi anestesi umum.Pembahasan: Kerusakan kateter adalah komplikasi yang dapat dikenali pada anestesi epidural, sering dikaitkan dengan trauma pada penusukan jarum epidural atau kekuatan yang berlebihan saat penarikan kateter. Pemeriksaan CT scan lebih sensitif daripada MRI dalam mendeteksi fragmen kateter dalam ruang epidural dan lebih sensitif dengan radiografi polos, terutama untuk fragmen kecil. Pengelolaan post operasi, potongan kateter epidural yang dianggap benda asing umumnya dianggap sebagai tidak aktif dan seharusnya tidak menghasilkan reaksi tubuh.Kesimpulan: Meskipun dikatakan potongan kateter epidural yang dianggap benda asing umumnya tidak menghasilkan reaksi tubuh. Pada kebanyakan kasus, standard penanganan terputusnya segmen kateter epidural, adalah dengan membiarkan dengan pengawasan sampai muncul gejala simptomatik. Namun, ada situasi di mana operasi pengangkatan harus dilakukan.
DAMPAK PERUBAHAN GUNA LAHAN TERHADAP KEMAMPUAN RESAPAN AIR (KASUS: KOTA SAMARINDA)
Authors: Warsilan Warsilan
Published: May 2019

As the capital of the province of East Kalimantan, Samarinda City developments has a rapid progress from year to year. Samarinda City Development has a tendency oriented towards infrastructure development without regard to the existence of the quality of the existing environment. Imbalance of development in Samarinda city is to start decreasing the water catchment area, so its make increasing intensity of flood in the Samarinda City. The purpose of this study was to analyze the impact of changes in land use in the Samarinda city on the ability of the water catchment area. This research method using descriptive approach, the data collection system of primary and secondary. Intensity flood in the Samarinda city  is increasing from year to year, this condition happened as a problem that always occurs during the rainy season. Current development trends, always take an area that should be an infiltration  area for Samarinda City. Culture and inadequate infrastructure conditions such as lack of system of drainage and polder, was another factor causing the high intensity of flood  in Samarinda City. Therefore, the relevant regulations development guidelines for Samarinda  City must consider all aspects of planning, in this case especially the important of a balance of cultivated land and protected areas or zones.Keywords: Changes in land use; intensity of puddles; Samarinda