bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing supportive care for patients with metastatic lung cancer in the era of precision oncology.
Authors: Hsu Kelly , Sequist Lecia V. , Jackson Vicki A. , Park Elyse R. , Rabideau Dustin , Greer Joseph A. , Temel Jennifer , Petrillo Laura A 
Published: June 2022

TPS12150 Background: Targeted therapy improves survival for patients with oncogene-driven non-small cell lung cancer (NSCLC). However, metastatic NSCLC remains incurable and patients often experience uncertainty about what to expect from their long and unpredictable illness trajectories. The aim of this trial is to pilot test a supportive care intervention that blends palliative care and survivorship for patients with metastatic oncogene-driven NSCLC. Methods: We will conduct a pilot randomized, controlled trial to evaluate the feasibility, acceptability and preliminary efficacy of a novel supportive care intervention for patients with metastatic oncogene-drive NSCLC. We will enroll 90 patients with a recent (within 6 months) diagnosis of metastatic NSCLC with a mutation in EGFR, ALK, ROS1 or RET genes who are receiving targeted therapy. We will enroll the first ten patients in an open pilot and we will refine the intervention and study procedures based on pilot findings. We will randomize the remaining 80 patients 1:1 to the intervention or a usual care control. Participants randomized to the intervention arm will have four monthly visits with a palliative care clinician who has been trained to address the supportive care needs of patients with long illness trajectories. Sessions will cover 1) rapport building and baseline symptom and psychosocial assessment; 2) coping support and healthy lifestyle promotion; 3) cultivation of prognostic understanding; and 4) exploration of goals and values. Patients in both arms will complete surveys including secondary outcome measures at baseline, 12, and 20 weeks post-enrollment. The primary outcome of the study is feasibility of the palliative care intervention, defined as at least 60% enrollment among eligible patients and 75% completion of all four sessions and three surveys. We will also assess acceptability using measures of satisfaction and comfort with the intervention. We will evaluate the preliminary effects of this intervention on the following outcomes to inform a future large-scale efficacy trial: 1) distress related to prognostic uncertainty and 2) prognostic awareness (using the Prognostic Awareness Questionnaire: 34-item validated measure with items about likelihood of cure and impact of prognostic awareness on decisions, behaviors and mood); 3) confidence in chronic disease management using the Self-Efficacy of Management of Chronic Disease scale; and 4) documentation of discussions about goals and values in the medical record. We will analyze change within and between groups at 12 and 20 weeks using linear mixed models, controlling for baseline values and relevant demographic and clinical factors. Study accrual to the open pilot phase began in February 2022. Current enrollment: n = 0. Clinical trial information: NCT04900935.
Natural history study for children and adults with rare solid tumors.
Authors: Varghese Diana Grace , Smith Hannah , Ahmed Shadin , Thomas B. J. , Bernstein Donna , Raygada Margarita , Lockridge Robin , Glod John , Del Rivero Jaydira , Reilly Karlyne , Widemann Brigitte C. , Wedekind Malone Mary Frances 
Published: June 2022

TPS1600 Background: Rare cancers is defined as fewer than 15 cases per 100,000 people per year and account for 27% cancers diagnosed and lead to 25% of cancer-related deaths. Nearly 13% (1 in 8) of all cancers diagnosed in adults ages 20 and older are rare. All pediatric cancers are rare and approximately 12,600 children under the age of 20 years are diagnosed with cancer each year. Rarity of these diseases has caused a stagnation in understanding the tumor biology and developing newer therapies. Initiatives like Orphan Drug Act (1983) and Rare Disease Act (2002) has led to improvement in funding and research about these rare tumors. The Cancer Moonshot Research Initiative funded My Pediatric and Adult Rare Tumor (MyPART) network (cancer.gov/mypart) in the NCI Pediatric Oncology Branch and launched a longitudinal Natural History Study for Children and Adults with Rare Solid Tumors (NCT03739827). Methods: A prospective study to evaluate the natural history of rare pediatric and adult solid tumors comprehensively and longitudinally. Patients of any age with a rare solid tumor (<15 cases per 100,000 people per year) are eligible. Patients with germline mutation who are at risk of developing these tumors or relatives of participants are also eligible. Patients can participate from home or are are invited to NIH for annual evaluations. Participants complete individual medical history, family history, patient related-outcomes measurements (PROs) and provide samples (blood, saliva) for DNA analysis. Tumors are analyzed using a 500+ gene panel (TruSight500, Illumina Panel) and undergo a comprehensive genomic and epigenomic analysis. Participants invited to NIH undergo a clinical evaluation, genetic counseling, blood collection (standard clinical labs, germline DNA/RNA, immune phenotypes, cytokines, exosomes), and imaging studies, as indicated. The goals of this study are to 1) Estimate and define the clinical spectrum of rare cancers 2) Evaluate and follow biological relatives of patients with rare tumors or carriers of germline genetic variants that predispose to development of rare tumors 3) Develop a better understanding of these diseases in an effort to develop a) Novel therapeutic interventions, b) Preventive/screening guidelines, c) Endpoints for future clinical trials, and d) Relevant patient reported outcomes that can improve our understanding of patients psychosocial and functional needs. Subprotocols under this protocol for children and adults include adrenocortical cancer (NCT04447014), neuroendocrine neoplasms (NCT04488263) and Chordoma (NCT0391046) to gather tumor specific data. Study accrual is ongoing. Clinical trial information: NCT03739827.
Telehealth weight loss program for breast cancer survivors is feasible and acceptable: Preliminary results of pilot clinical trial.
Authors: Tchou Julia C. ,   UPENN Authors' Group
Published: June 2022

TPS1603 Background: Current weight loss programs for breast cancer survivors utilize a hybrid of in-person visits or individualized telephone-based sessions modeled after the Diabetes Prevention Program. Telehealth may be an effective and efficient means of communicating with patients who otherwise cannot participate in in-person visits. To test this concept, we conducted a pilot single-arm study (NCT04855552) to examine the feasibility and acceptability of a weight loss group program via telehealth for breast cancer survivors. Methods: Patients > = 18 years with ECOG performance 0 or 1, a BMI of ³ 25 kg/m2, and completion of adjuvant radio- and/or chemo-therapy > 6 months were eligible. Patients attended weekly zoom teleconference counseling grouped sessions either at noon or 5 pm led by a licensed clinical psychologist for 20 weeks followed by sessions in weeks 22 and 24. Patients were encouraged to use MyFitnessPal.com, an online tool, to monitor calorie intake and physical activity and digital scales to monitor weight to share with study staff to enhance accountability and provide opportunity for feedback. Feasibility was defined as a ratio of enrolled/eligible patients ≥50%. Acceptability was assessed from surveys pre- and post-treatment, and qualitatively from exit interviews. Secondary endpoints included changes in Quality of Life-Breast Cancer Patient (QOF-BC), Patient Health Questionnaire (PHQ-9), and percent weight loss from baseline to 24 weeks. Results: Clinical characteristics of patients are summarized in Table. The ratio of enrolled (n = 12)/eligible (n = 23) participants was 52% thus confirming study feasibility. One patient dropped out after 2 sessions. Qualitative results from exit interviews showed that 7/9 patients rated the telehealth format as “extremely acceptable”. Surveys also indicated that the format and delivery of the program remained acceptable across most domains with no significant changes, except an increase in “approval” from 4.1 to 4.7 ( p= 0.05). Patients’ mood improved on the PHQ-9 from 4.2 to 1.2 (p = 0.03), and QOL-Physical Wellbeing improved from 56.9 to 66.3 (p = 0.004). Overall, 199 of 236 participant-sessions (84%) were attended. Percent weight loss was 6.5% +/- 2.5%. Conclusion: This proof-of-concept weight loss program was feasible and acceptable for our patients yielding improvements in QOL, mood, and a clinically significant weight loss over 6-months. This group-based video approach represents an intervention strategy that could be widely-disseminated and may provide stronger accountability/support than a one-on-one approach in some patients. Future work is aimed at refining strategies to increase patient enrollment/retention. Clinical trial information: NCT04855552. [Table: see text]
Phase II multicentric Italian trial on repositioning of the antipsychotic drug chlorpromazine and its combination with temozolomide in patients with MGMT unmethylated glioblastoma: The RACTAC trial.
Authors: Lombardi Giuseppe , Paggi Marco Giorgio , Matteoni Silvia , Villani Veronica , Benincasa Dario , Abbruzzese Claudia , Cerretti Giulia , Padovan Marta , Caccese Mario , Silvani Antonio , Pace Andrea 
Published: June 2022

TPS2073 Background: The poor prognosis of patients affected by glioblastoma (GBM) prompts the search for new and more effective therapies, particularly for GBMs with unmethylated MGMT. In this regard, drug repurposing, can represent a safe and inexpensive way to bring novel pharmacological approaches from bench to bedside. Chlorpromazine, a medication in use since six decades for the therapy of psychiatric disorders, shows in vitro features that make it eligible for repositioning in GBM therapy. In our experimentation on six GBM cell lines, chlorpromazine inhibited cell viability in an apoptosis-independent way, induced polyploidy, reduced cloning efficiency as well as neurosphere formation and downregulated the expression of stemness genes. Notably, we found that chlorpromazine synergized with temozolomide, in reducing cell viability and strongly cooperated in reducing cloning efficiency and inducing cell death in vitro for all the GBM cell lines assayed. Methods: With these assumptions, we started a multicentric single arm Phase II clinical trial on newly diagnosed GBM patients with unmethylated MGMT by adding chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol. The experimental procedure involves the combination of CPZ with standard treatment with TMZ in the adjuvant phase of the Stupp protocol after radiochemotherapy combination. CPZ is administered orally at a dose of 50 mg/day – GG 1-28 – of every cycle of the adjuvant treatment with TMZ. At present, 38 patients out of 41 patients planned have been enrolled. Clinical trial information: NCT04224441.
A study of neo-adjuvant and adjuvant ofra-vec (VB-111) for treatment of surgically accessible recurrent GBM.
Authors: Wen Patrick Y. , Brenner Andrew J. , Butowski Nicholas A. , Rachmilewitz Minei Tamar , Harats Dror , Cloughesy Timothy Francis 
Published: June 2022

TPS2075 Background: Ofranergene obadenovec (ofra-vec, VB-111) is an anti-cancer gene based immune activator and targeted vascular disruptor. The dual mechanism of action triggers a broad antiangiogenic effect and induces of a tumor directed immune response. A previous study demonstrated a survival benefit for patients with recurrent glioblastoma (rGBM) treated with ofra-vec monotherapy, that was continued after progression in combination with bevacizumab. Glioblastoma is an immunologically “cold” microenvironment which fosters immunosuppression and antagonizes anti-tumor immune responses. The role of T-cell infiltration in combating cancer has been increasingly recognized and associated with improved participant outcomes. Based on these observations, this study will assess the hypothesis that neoadjuvant use of ofra-vec will lead to a statistically significant increase in tumor infiltrating T lymphocyte (TIL) density within the tumor and enhanced systemic tumor-specific T cell responses. Methods: Study NCT04406272 is a multicenter, randomized, blinded, placebo-controlled, phase 2 surgical trial to evaluate early immunologic pharmacodynamic parameters for the viral cancer therapy ofra-vec in rGBM. 45 participants with rGBM indicated for resection will randomized to one of three treatment arms: Neoadjuvant Arm: intravenous ofra-vec prior to resection, and ofra-vec every 6 weeks after resection. Adjuvant Arm: placebo prior to resection, and ofra-vec every 6 weeks afterwards. The control arm will receive placebo prior to resection followed by standard of care. Upon evidence of contrast-enhancing progression, bevacizumab may be initiated as needed for supportive care; however, ofra-vec will continue until progression is supported at two consecutive time points. Tumor samples will be obtained and archived at the time of surgery, and blood samples will be obtained as pharmacodynamic markers throughout the study to allow DNA sequencing of T cells. The primary endpoint is to evaluate the influence of neoadjuvant ofra-vec on TIL density. Other endpoints include safety and tolerability, peripheral T cell response, 6mPFS and OS. Study is open for enrolment. Clinical trial information: NCT04406272.
DSP-0390, an oral emopamil binding protein (EBP) inhibitor, in patients with recurrent high-grade glioma: A first-in-human, phase 1 study.
Authors: Reardon David A. , Narita Yoshitaka , Arakawa Yoshiki , Goldlust Samuel A. , Ansstas George , Mei Jian , Dow Edward , Seki Masataka , Furuta Yudai , Song Gregory , Colman Howard 
Published: June 2022

TPS2077 Background: The brain’s cells are fully dependent on their own de novo biosynthesis of cholesterol as the blood-brain barrier prevents its uptake from the circulation. In normal glial cells, proper regulation of cholesterol synthesis depends on its cell density and is turned off when the cell density exceeds a certain level. On the other hand, gliomas maintain high levels of cholesterol synthesis to support abnormal growth under any condition. Upregulation of cholesterol synthesis genes is associated with decreased survival in patients with glioblastoma (GBM). Therefore, gliomas are potentially sensitive to cholesterol synthesis inhibition. DSP-0390, an investigational small molecule, is an inhibitor of EBP, an enzyme in one of the last and crucial steps of cholesterol biosynthesis. By inhibiting de novo cholesterol synthesis, cytotoxicity can be induced more selectively against hyperproliferative GBM cells. DSP-0390 has shown significant antitumor activity in orthotopic xenograft models of human GBM (data on file). Methods: DSP-0390 will be evaluated in a phase 1 study in patients with recurrent, high-grade glioma (NCT05023551). Key eligibility criteria: age ≥18 years; Karnofsky Performance Status score ≥70%; and adequate renal, hepatic, and hematologic function. Patients must not have multifocal disease, leptomeningeal metastasis or extracranial metastasis, abnormal electrocardiograms, or significant cardiovascular disease. In Dose Escalation, 21–30 patients with World Health Organization (WHO) grade III or IV malignant glioma who progressed after ≥1 prior therapy will be enrolled. Dose level enrollment will be guided by a Bayesian Logistic Regression Model until identification of the maximum tolerated dose or recommended dose for expansion. Dose Expansion for clinical activity will enroll approximately 20–40 patients with WHO grade IV GBM who progressed after primary therapy and have measurable disease. Patients will receive oral DSP-0390 once daily. Study endpoints include safety (treatment-emergent adverse events [AEs], serious AEs, and dose-limiting toxicities), efficacy (6-month progression-free survival [PFS], objective response, PFS, duration of response, and 12-month overall survival), pharmacokinetics (PK), and pharmacodynamic biomarkers. This study is currently recruiting in the United States and Japan. Clinical trial information: NCT05023551.
ZENYTH-ESO: Master protocol to assess the safety and recommended phase II dose of next generation NY-ESO-1-specific TCR T-cells in HLA-A*02 patients with synovial sarcoma and myxoid/round cell liposarcoma [Substudy 3, GSK4427296].
Authors: Araujo Dejka M. , Ladle Brian H. , He Kai , Powers Benjamin , McGillivray Amanda , Mitrica Ionel , Liu Wenlei , Patel Nitin , D'Angelo Sandra P. 
Published: June 2022

TPS2681 Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T-cell therapy expressing an affinity-enhanced T-cell receptor (TCR) to improve recognition of cancer cells expressing NY-ESO-1 and/or LAGE-1a. Next generation NY-ESO-1 TCR T-cell therapy, GSK4427296, utilizes the same TCR as lete-cel, as well as an epigenetic reprogramming process (Epi-R) developed by Lyell Immunopharma to alter the phenotypic T-cell profile of the manufactured product, and is intended to increase the proportion of cells with properties of durable stemness. T cells with properties of durable stemness are able to proliferate, persist, and self-renew with anti-tumor functionality. A first-time-in-human master protocol (NCT04526509) is underway to evaluate the safety, tolerability, and recommended phase II dose (RP2D) of next generation NY-ESO-1 TCR T-cell therapies. Substudy 3 is added to this master protocol to assess GSK4427296 in patients with advanced synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCLS). Methods: This substudy includes a dose confirmation stage to assess RP2D and a dose expansion stage, aiming to dose 10 participants at the RP2D. Key inclusion criteria: age ≥18 years; measurable disease per RECIST v1.1; HLA-A*02:01, A*02:05, or A*02:06 positivity; NY-ESO-1/LAGE-1a tumor expression; advanced (metastatic/unresectable) SS with t(X;18) translocation or MRCLS with a translocation involving DDIT3 and/or FUS and/or EWSR1 genes; and anthracycline-based therapy receipt/completion/intolerance. Key exclusion criteria: prior malignancy that is not in complete remission or clinically significant systemic illness; prior receipt of gene or allogenic stem cell/solid organ transplant; and central nervous system metastases. Primary endpoints: safety (adverse events) and tolerability (dose-limiting toxicities). Secondary endpoints: investigator-assessed overall response rate, duration of response, maximum transgene expansion (Cmax), Tmax, and AUC(0-t). Analyses will be descriptive. The master protocol is open for recruitment. Clinical trial information: NCT04526509.
Phase 1/2 dose escalation study of NUV-422, a potent inhibitor of cyclin-dependent kinases 2, 4, and 6, in recurrent or refractory (r/r) high-grade gliomas (HGG) and solid tumors.
Authors: Wen Patrick Y. , Rodon Ahnert Jordi , Powderly John D. , Colman Howard , Matheny Shannon L. , Golsorkhi Anthony A. , Bihani Teeru , Zhang Yan , Kaley Thomas Joseph 
Published: June 2022

TPS3173 Background: CDKs that govern the G1-S transition of the cell cycle (CDK2, CDK4 and CDK6) are deregulated in many cancers. CDK2 expression, in particular, is associated with worse overall survival in glioblastoma (GB), disease-free recurrence in prostate cancer, and resistance to approved CDK4/6 inhibitors (CDK4/6i) in breast cancer. These provide rationale for inhibition of CDK2/4/6 as a potential novel therapeutic strategy in these cancers. NUV-422 is a potent (low nM) small molecule CDK2/4/6i with limited activity against CDK1, a target potentially associated with toxicities in other CDKi. Preclinical studies have shown that NUV-422 has favorable blood-brain barrier penetration, inhibited growth of multiple glioma cell lines in vitro, and exhibited antitumor activity in GB xenograft models. NUV-422 also exhibited antitumor activity in multiple patient-derived xenograft (PDX) models of HR+ HER2- mBC resistant to CDK4/6i, and PDX models of prostate cancer resistant to anti-androgens. Methods: NUV-422-02 (NCT04541225) is a phase 1/2, first in human, open label, multicenter study to evaluate single-agent NUV-422 (given orally) in patients with advanced solid tumors (r/r HGG, r/r HR+ HER2- mBC, or r/r mCRPC). The Ph 1 dose escalation will use a 3+3 design to evaluate safety, tolerability, and PK of NUV-422 and establish the recommended phase 2 dose (RP2D). Ph 1 also includes a randomized surgical substudy to characterize PK and pharmacodynamics (PD) of preoperative NUV-422 in resected GB tumor tissue. After the RP2D is identified, parallel enrollment into phase 2 expansion cohorts will begin. Cohort 1 will evaluate isocitrate dehydrogenase wild type (IDH-WT) GB. Cohort 2 will evaluate HR+ HER2- mBC (without active brain metastases); Cohort 3 will evaluate mCRPC; and Cohort 4 will evaluate HR+ HER2- mBC with active brain metastases. The Ph 2 primary endpoint is objective response rate. Secondary efficacy endpoints include clinical benefit rate, duration of response, progression-free survival, and overall survival. Response assessments will be based on response criteria appropriate to the tumor type (HGG [RANO]; HR+HER2- mBC [RECIST 1.1 or RANO-Brain Metastases]; mCRPC [RECIST 1.1, PCWG3, prostate-specific antigen decrease]). Blood, urine, or tumor tissue will be obtained to assess safety, PK, PD, and for additional exploratory analyses to characterize NUV-422 mechanism of action. Enrollment was initiated in December 2020, and dose escalation is ongoing. The NUV-422 program will also be expanded in 2022 to include additional studies in mBC and mCRPC in combination with standard of care treatments. Clinical trial information: NCT04541225.