bluuebunny/crossref_metadata_2025_split huggingface dataset:
Objective assessment of fatigue, sleep and insomnia in breast cancer survivors on estrogen deprivation therapy.
Authors: Fowler Lauren A. , Myers Jamie S. , Re Shelby , Tedrick Maddie , Hudson Matthew F. , Stephenson Joe , O'Rourke Mark Allen 
Published: June 2023

TPS12145 Background: Fatigue, insomnia and sleep problems are common among breast cancer survivors (BCS). These symptoms remain underassessed, underreported and undertreated. Validated and objective measures of sleep metrics have yet to be widely incorporated into BCS studies to help examine the role that these play on patient patient reported fatigue and insomnia. While more than 50% of BCS experience fatigue and insomnia, most research on BCS fatigue is limited to short-term, self-report data that does not objectively assess sleep metrics. Estrogen Deprivation Therapy (EDT) has been shown to exacerbate sleep problems and contribute to perceptions of fatigue and insomnia, yet there is a paucity of research examining the specific effects of EDT on sleep metrics over time, especially objective measures. Wrist actigraphy is a non-invasive, objective measure of rest/activity cycles and sleep via a wrist-worn device. This study utilizes a novel instrument, called Readiwatch (Fatigue Sciences). It is widely validated in the military and in industry but has not been used in patient studies. The Readiwatch assesses fatigue and estimates cognitive performance, based on the Sleep Activity and Task Effectiveness (SAFTE) model developed in conjunction with the Department of Defense in 2004. The Readiwatch syncs with the Fatigue Avoidance Scheduling Tool (FAST) app on the participant’s smartphone to provide a score, called Readiscore, based on previous sleep and activity. It has been shown to have greater than 92% accuracy with lab polysomnography results. The Readiscore also serves as a “cognition” measure that represents the person’s cognitive capacity based on sleep metrics. This novel, objective feedback to the BCS could be very accessible and useful in community medical practice. Methods: This single-center, pilot study of BCS, receiving endocrine therapy, possessing a smartphone and Scoring >8 on the Insomnia Severity Index (ISI), has enrolled 25 of 50 planned participants. Participants wear the Readiwatch for two months to objectively assess their sleep metrics. Patient reported levels of fatigue and insomnia will be assessed prior to, midway, and following the two-month period. Participants document their self-reported experiences through surveys and track their own sleep and fatigue metrics using their smartphone app. At the conclusion of the study participants are provided with personalized feedback about their sleep metrics, along with detailed information related to sleep hygiene. Data analysis will model the effect of actigraphy fatigue measures on reported pain, anxiety, depression, and cognitive impairment and will also examine sleep metrics, perceptions of fatigue and insomnia scores in relation to type of EDT the patient is currently undergoing to determine if there are specific types of adjuvant therapy that are associated with fewer fatigue and insomnia problems.
Prospective observational study to evaluate lemborexant utility in insomnia among women with breast cancer (WJOG14921B, LUNAR study).
Authors: Ozaki Yukinori , Hosonaga Mari , Futamura Manabu , Kurozumi Sasagu , Onoe Takuma , Iwasa Tsutomu , Kamio Hidenori , Terata Kaori , Watanuki Rurina , Masuda Hiroko , Saeki Yoshinori , Kitano Shigehisa , Sakamaki Kentaro , Nonogaki Kiyomi , Yoshimura Yuta , Kawai Daisuke , Takano Toshimi 
Published: June 2023

TPS12148 Background: Insomnia occurs in approximately 60% of cancer patients. The importance of early intervention to treat insomnia has been advocated because insomnia may be associated with poor prognosis, early discontinuation of treatment and decreased quality of life. It has been reported that breast cancer patients receiving endocrine therapy have the highest rate of insomnia among all cancer patients due to vasomotor symptoms (ie, hot flashes) and comorbid symptoms associated with fatigue and depression. Insomnia has also been found to occur in patients with metastatic/recurrent breast cancer. Lemborexant (LEM) is a dual orexin receptor antagonist, which has been shown to be effective for insomnia patients without malignancies. In clinical practice, while LEM has been administered to cancer patients with insomnia, there are no prospective data. The aim of this study is to evaluate prospectively whether LEM improves insomnia in patients with breast cancer receiving endocrine therapy. Methods: This is an open-label, prospective, multicenter, observational study to evaluate efficacy and safety of LEM to treat insomnia in patients with breast cancer receiving endocrine therapy [UMIN000047718]. The primary endpoint is change from baseline of total Insomnia Severity Index (ISI) score at 1 month. Secondary endpoints include change from baseline of cancer fatigue scale scores, EORTC QLQ C-30 and BR23 score, and Patient Health Questionnaire-9 score after 1 month and 3 months, change from baseline in total sleep time and sleep efficiency using an electronic sleep diary after 2 weeks, 1 month and 3 months, and safety profile. Exploratory endpoints include biomarker analysis including evaluation of cytokines and orexin A levels, and evaluation of sleep parameters using Oura ring, which is a ring-type wearable device. The primary endpoint will be assessed by the Wilcoxon signed-rank test. Total sample size will be 70 patients (adjuvant cohort: 50 patients, recurrent and/or metastatic cohort: 20 patients). Patients ≥20, meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition for Insomnia Disorder and ISI score ≥10 will be eligible. LEM 5mg will be administrated orally every night. Dosage of LEM will follow clinical practice and the Japanese LEM label. Enrollment began in September 2022; 14 patients have been recruited in adjuvant cohort as of January 2023. Clinical trial information: UMIN000047718 .
Korean Precision Medicine Networking Group study of molecular profiling guided therapy based on genomic alterations in advanced solid tumors (KOSMOS) II (KCSG AL 22-09).
Authors: Kim Sun Young , Kim Jee Hyun , Kim Tae-Yong , Park Sook Ryun , Yoon Shinkyo , Lee Soohyeon , Lee Se-Hoon , Kim Tae Min , Han Sae-Won , Yun Hongseok , Lee Sejoon , Kim Jihun , Choi Yoon-La , Choi Kui Son , Chae Heejung , Ryu Hyewon , Lee Gyeong-Won , Zang Dae Young , Ahn Joong 
Published: June 2023

TPS1608 Background: Next-generation sequencing (NGS) has been introduced to many Korean institutions as molecular diagnostics for cancers since 2017, when it was reimbursed by the National Health Insurance Service. However, molecularly-guided treatment (MGT) options based on NGS results have been limited due to the strict regulation for prescribing outside of the approved indication, lack of clinical trial availability, and limited access to molecular tumor boards (MTB) in most institutions. Given our previous KOSMOS study results, which showed MGT was available for 54% (124/198) of patients based on local NGS (ESMO Open 2022;7(6, Suppl 1);100653), KOSMOS-II study was designed to demonstrate MGT would be feasible and effective via a nation-wide precision medicine platform. Methods: This national, prospective, pragmatic, multi-cohort study comprised of a framework to screen pts with metastatic solid tumors for actionable genetic alterations (GA) based on local NGS testing and to recommend MGT by a remote and centralized MTB held weekly or biweekly. MGT can be one of the following options: Tier 1, the therapeutic use of investigational drugs targeting GAs including ALK, EGFR, ERBB2, BRAF, FH, ROS1, RET, or high tumor mutational burden; Tier 2, drugs that are allowed for treatment outside of the approved indications by the National Health Insurance; Tier3, clinical trials matched for GA recommended by MTB. To estimate the proportion of patients receiving MGT to be 50±3.25% with 95% confidence interval, we will enroll 1,000 pts, considering 5% drop-out rate. The clinical benefit rate of MGT beyond 16±2 weeks is the second co-primary endpoint, which is expected to be 30% with type I error of 5% and 90% power. Pts must have progressed ≥ 1 or more lines of therapies; have undergone NGS testing; are able to provide the Variant Call Format (vcf) file of the NGS results. MTB determines clinical actionability of GA and recommends MGT if possible, according to Tier 1,2, or 3. The vcf files and matched clinical information will be deposited to the repository of National Center Center Korea and will be curated in a de-identified clinico-genomic database. As of Feb 2023, 139 of planned 1,000 have been enrolled. Clinical trial information: NCT05525858 .
Screening for high frequency malignant disease (SHIELD).
Authors: NGUYEN HA , Cotton Lindsey , Vento-Gaudens Erika , Raymond Victoria M. , Eagle Craig 
Published: June 2023

TPS1610 Background: Insufficient adherence to guideline recommended cancer screening undermines the effectiveness of current modalities to improve cancer related outcomes, resulting in an unmet clinical need. Implementation of a convenient blood-based cancer screening option, utilizing a test with high sensitivity and specificity, has the potential to address this unmet need. We aim to evaluate the performance of a blood-based multi-cancer screening test in a population of screen eligible individuals across multiple cancer types, encompassing a diverse representation of racial and ethnic groups. Methods: SHIELD (Screening for High Frequency Malignant Disease; NCT#05117840) is a prospective, observational, multi-center basket study in the United States and Europe designed to recruit individuals undergoing screening across multiple cancer types. The study’s primary objective is to evaluate the performance of a blood-based multi-cancer screening test (GuardantLUNAR-2, Guardant Health, US) to detect cancer in screen-relevant individuals compared to the reference standard cancer screening modality. Each study cohort represents a unique cancer type(s). Eligible individuals consent to whole blood collection within 90 days of the standard of care screening for the respective cancer type. Clinical diagnoses, e.g., cancer, are made per standard of care. Primary outcomes: sensitivity, specificity, negative and positive predictive value of the blood-based multi-cancer screening test. Secondary outcomes: number of screen-detected cancers, early and late-stage screen-detected cancers per 1000 screened individuals. One- and two- year clinical outcomes are collected by implementing HIPAA compliant, patient-level linkage of trial data with real-world data sources (Medidata, USA) to which patients consent subsequent to main study consent. Cohort A: Lung cancer screening. Eligibility is aligned with USPSTF screening recommendations; age 50-80 years with > 20 pack-year smoking history who are current smokers or quit within the past 15 years, without any history of cancer or preinvasive lung lesions, and without recent surgery or trauma. This cohort will enroll 9,000 subjects over 24 months at up to 120 global sites. This cohort was initiated in January 2022. As of January 2023, 94 study sites have been activated with 4,977 individuals consented and 4,866 individuals enrolled (defined as study blood sample collected). To date, 4679/4977 (94%) individuals consented to the linkage process. Cohort A is on track to meet enrollment targets by the end of 2023 and on track for final primary outcome data collection by December 2024. Clinical trial information: NCT05117840 .
The PLATON Network: An interactive platform for precision oncology.
Authors: Al-Batran Salah-Eddin , Goetze Thorsten Oliver , Saborowski Anna Lena , Agaoglu Nihat Bugra , Broeckling Sebastian , Dreyling Clara , Lorenzen Sylvie , Modest Dominik Paul , Schuler Markus K , Westphalen Benedikt , Wild Peter , Zäpf Bianca , Vogel Arndt 
Published: June 2023

TPS1613 Background: To increase the access of patients to precision oncology and personalized medicine, we need not only to undertake molecular profiling but rather we need to interlink patients, physicians and researchers using modern technological opportunities, increasing the likelihood of providing new therapies to patients with suitable targets. The PLATON Network (NCT05489250, IKF-T008) addresses these important issues. Methods: The PLATON Network (PLATON) is an interactive structure aiming at improving personalized medicine for all tumor entities (starting with upper GI tumors). The goal of the PLATON Network is to provide a platform for connecting medical practitioners, researchers and patients to personalized cancer treatments. The platform combines comprehensive molecular profiling, data on active clinical trials, remote data access with networking solutions, implemented substudies and associated educational and discussion forums. The main elements of PLATON are: a Platform-study design, an interactive Cloud-based WebApp, Networking, a Molecular Pathology Case Discussion Board, an educational forum, and a BioDataBank. The network will be composed of a global network of cancer centers and cancer specialists who can submit genomic data of their patients to PLATON. The WebApp allows members and associated scientists to view each other's current patients' clinical and molecular data and get into contact with the treating physicians or identify patients for ongoing biomarker-driven clinical trials using advanced algorithms. The PLATON Network also offers molecular testing via Foundation CDx and CDx Liquid for standardized NGS testing and functions as an umbrella for substudies within the platform design. PLATON enrolls patients during first line treatment and collects information on routine clinical data (baseline data, medical history, histopathology reports, treatment decisions, etc.). During follow up, all anti tumor therapy lines, tumor response and survival data are recorded. Importantly, quality of life data is captured monthly under therapy (with EORTC QLQ-30,-BIL21, -HCC18, -PAN26, -STO22 and EQ-5D-5L) and at further follow up (with EQ-5D-5L). So far, 110 cancer centers have joined the PLATON network. Over 200 patients with upper GI tumors received comprehensive molecular profiling and 162 cases were reviewed and discussed in the Molecular Pathology Case Discussion Board. Five sub-projects/-studies have been initiated under the umbrella of PLATON. The educational forum is in the planning stage. PLATON is conducted by the Institute of Clinical Cancer Research (IKF) in Frankfurt with the supervision of an independent scientific steering committee.
A first-in-human pharmacodynamic evaluation of dual polyamine depletion for patients with high-grade gliomas.
Authors: Riviere-Cazaux Cecile , Neth Bryan , Kizilbash Sani Haider , Burns Terry C 
Published: June 2023

TPS2082 Background: No drug has improved survival for patients with high-grade gliomas (HGGs) since temozolomide in 2005. Relatively little is known about the live response of in situ gliomas to therapeutic intervention. Phase 0 studies that leverage access to the live human glioma in situ, including via microdialysis to sample the live glioma microenvironment, provide an attractive and feasible solution to this problem. We performed intraoperative microdialysis to evaluate the extracellular metabolome of divergent regions in 15 HGG resections. Our data revealed a conserved metabolic signature of HGGs and a novel glioma-associated metabolite, guanidinoacetate (GAA). Pathways enriched in this tumor signature included methionine and polyamine metabolism. Although GAA is typically converted to creatine, we hypothesize that the high flux of ornithine through ornithine decarboxylase (ODC) results in excess GAA accumulation. As such, in a Phase 0 trial, we will evaluate in situ glioma responses to polyamine depletion via ODC inhibition (Difluoromethylornithine, DFMO), with or without blockade of polyamine uptake (AMXT 1501), to identify candidate extracellular biomarkers of target engagement and cytotoxicity. Methods: Patients will be recruited who are undergoing a clinically indicated subtotal resection for a known or suspected high-grade glioma (NCT05717153). At the end of the surgery, two microdialysis catheters will be implanted for post-operative microdialysis, one in residual tumor and one in brain adjacent to tumor for an internal control. Beginning on post-operative day (POD) 1, patients will be randomized to one of the following three groups, including administration of vehicle, DFMO (500 mg, PO, BID) and AMXT 1501 (600 mg, PO, BID): 1) DFMO + AMXT 1501 (POD1-5); 2) Vehicle (POD1–POD2), followed by DFMO + AMXT 1501 (POD3-POD5); 3) DFMO alone (POD1–POD2), followed by DFMO + AMXT 1501 (POD3- POD5). Throughout this time, extracellular metabolite levels of polyamines, guanidinoacetate, and glutamate will be quantified from microdialysate collected every two hours from intraoperatively implanted 100 kDA microdialysis catheters. The primary outcome of this study is to determine how polyamine depletion impacts extracellular intratumoral guanidinoacetate abundance. The secondary outcomes of this study are to (1) determine the impact of polyamine depletion on polyamine abundance and the global extracellular metabolome within live human gliomas, in situ, and (2) assess the feasibility of longitudinal microdialysis for pharmacodynamic analysis within live human gliomas in situ in the post-operative setting. Clinical trial information: NCT05717153 .
Low-intensity focused ultrasound with systemic microbubble oscillators for blood-brain barrier disruption for liquid biopsy in glioblastoma (LIBERATE).
Authors: Ahluwalia Manmeet Singh , McDermott Michael W , Burns Terry C , de Groot John Frederick , Lee John Y.K. , Mogilner Alon , Schwartz Theodore , Shah Bhavya , Bettegowda Chetan , Ozair Ahmad , Khosla Atulya Aman , Sahgal Arjun , Mishra Mark V. , Achrol Achal , Lipsman Nir , Woodworth Graeme 
Published: June 2023

TPS2084 Background: Liquid biopsy in glioblastoma (GBM) is hindered by a lack of requisite circulating-free DNA (cfDNA) levels in blood due to the blood-brain barrier (BBB). This results in challenges to the identification of blood-based biomarkers and the development of novel biomarker-driven systemic therapies. Real-time image-guided low intensity focused ultrasound (LIFU) combined with IV microbubble oscillators (DEFINITY), non-invasively causes BBB disruption (BBBD). This clinical trial aims to evaluate the utility of LIFU for increasing cfDNA in blood for liquid biopsy in GBM. Methods: LIBERATE is a prospective, multi-center, self-controlled, ongoing, pivotal trial evaluating safety and technical efficacy of LIFU for BBBD to increase cfDNA in blood for GBM. Patients aged >18-80 years with suspected GBM planned for tumor biopsy or resection at eleven centers in North America are being included. Patients with multifocal tumors or tumors arising from deep midline, thalamus, cerebellum, or brainstem are excluded. Patients are administered IV oscillating microbubbles for enhancing sonication, after which MR-guided BBBD using a 220 kHz LIFU device is performed with real-time acoustic feedback for effective cavitation. Before and after procedure, phlebotomies and MRI brain are performed to evaluate outcomes. The primary study endpoint is defined, per subject, as the ratio between their cfDNA level in blood 1-hour post-LIFU compared to cfDNA level in blood pre-procedure. The primary study hypothesis is that BBBD with LIFU leads to ≥2-fold increase in cfDNA in blood. The secondary hypothesis is that there exists ≥75% agreement between biomarker pattern in cfDNA sample from 1-hour post-LIFU sample and biomarker pattern in tumor tissue obtained later. The trial has been powered to evaluate both primary and secondary hypotheses. Based on an assumed true agreement rate of 91% and a one-sided alpha of 0.025, an exact test for binomial proportions provides a sample of N=50 with 84% power for the secondary hypothesis. Exploratory endpoints include (1) sensitivity of detection of known somatic mutations in cfDNA from blood samples collected before and after LIFU, (2) estimation of cfDNA levels post-LIFU in samples collected at 30 minutes, 1 hour, 2 hour, and 3 hour to determine time of greatest yield, (3) correlation of MRI parameters related to grading of BBBD and biomarkers positive in cfDNA from post-LIFU blood samples. Patient enrollment commenced in 2022 and 7 patients have been recruited by 02/13/2023. Clinical trial information: NCT05383872 .
Phase 1b multicenter study to evaluate CHM 1101 in patients with recurrent or progressive glioblastoma.
Authors: Litten Jason Blair , Ramakrishnan Aravind , Astrow Stephanie H. , Harrison Cassandra , Aliki Alex , Badie Behnam 
Published: June 2023

TPS2086 Background: Glioblastoma multiforme (GBM) is the most common and most aggressive primary brain tumor. More than 300,000 new cases are diagnosed globally with over 250,000 deaths each year (Sung H, et al. CA Cancer J Clin. 2021). Patients with recurrent GBM have a poor prognosis, with limited treatment options and a median survival of less than 1 year (Gallego. Curr Oncol, 2015). While prior attempts to treat GBM with chimeric antigen receptor (CAR) T-cells have been limited by tumor heterogeneity, chlorotoxin (CLTX)-directed CAR T-cells in mice demonstrated broad anti-tumor activity and prolonged survival with no off-tumor toxicity or antigen escape (Wang, et al. Sci Transl Med, 2020). CLTX, a 36–amino acid peptide identified in scorpion venom, selectively binds to malignant glioma cells through matrix metalloproteinase-2 (MMP2) and clinical administration of CLTX-based biologics has been well tolerated in patients (Mamelak, et al. J Clin Oncol, 2005, Patil, et al. Neurosurgery, 2019). CHM 1101 is the first CAR T to utilize CLTX as its tumor targeting domain for autologous CAR T-cell therapy. A single-center first-in-human phase 1 study of CHM 1101 in patients with recurrent GBM is ongoing. Methods: Clinical Trial NCT05627323 is a phase 1b, multi-center study of CHM 1101 in adult subjects with MMP2+ recurrent or progressive GBM after standard therapy. After leukapheresis and tumor resection, pts will receive CHM 1101 at Dose Level 1 (240 × 106 CAR T cells) or Dose Level 2 (440 x 106d CAR T-cells), divided across 3 once-weekly intracranial (intracavitary and intraventricular) administrations; after disease assessment at 28 days, additional doses of CHM 1101 can be administered on a weekly schedule. Eligible subjects have a prior histologically confirmed diagnosis of a grade 4 GBM, a grade 2 or 3 malignant glioma with radiographic progression consistent with a grade 4 GBM (IDH wild type), grade 4 diffuse astrocytoma (IDH mutant), or a unifocal relapse of GBM. MMP2+ tumor expression is confirmed by IHC (≥20% moderate/high MMP2 score [2+ or 3+]). The primary endpoint is safety; key secondary endpoints include feasibility, progression-free survival, overall survival, response rate (RANO criteria), and cellular kinetics. Recruitment is ongoing. Clinical trial information: NCT05627323 .