bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nurse AMIE: Addressing symptoms in rural patients with advanced cancer.
Authors: Truica Cristina I. , Schmitz Kathryn , Doerksen Shawna , Calo William , Stout Nicole Lynn , Wang Ming , Lengerich Eugene , Moss Jennifer , Vanness David J. 
Published: June 2022

TPS12148 Background: Prior research has shown that monitoring symptoms in advanced cancer patients may provide a survival benefit. Monitoring is a labor-intensive process that requires nursing staff response and visiting a medical office. This may be more challenging in rural areas, given staffing challenges and distances traveled for care. Lower density of supportive care services has been documented in rural as compared to urban settings in Pennsylvania and West Virginia. We have developed a computer tablet-based supportive care program, called Nurse AMIE, and are investigating its use in symptom management among cancer survivors. Our hypothesis is that a tablet-based supportive care program can improve overall survival of advanced cancer patients in rural Pennsylvania and West Virginia. Methods: This randomized controlled trial will recruit 344 patients residing in a rural county or zip code (RUCC 4-9 or RUCA 4-10) in Pennsylvania or West Virginia, who receive treatment for stage III-IV cancer, are 18 years or older, ECOG 0-3, are fluent in written and spoken English, have sufficient vision/hearing to interact with a computer tablet and staff, and have a clinician-defined life expectancy of 6 months or more. Exclusion criteria: patients on active treatment or behavioral or supportive care trials, or with medical or psychiatric conditions that would impair ability to test study hypotheses. Patients will be randomized on a 1:1 basis to receive either Nurse AMIE or a binder with written supportive care materials. Intervention participants will be asked to log into Nurse AMIE daily, where they will interact with a nurse avatar and answer symptom questions (focusing on sleep, fatigue, pain, and distress). They will receive an empathic response to symptoms and be offered evidence based, guideline concordant self-care interventions to address symptoms (including exercise, nutrition, guided meditation, cognitive behavioral therapy videos, and soothing music). Once weekly, patients will answer 21 questions from the Pro-CTCAE survey. All symptom data will be loaded into a dashboard reviewed daily by study staff. Pain or distress scores of 7+ (out of 10) will be communicated to the care team through the EMR. The trial is powered to detect a 19% difference in overall survival at 2 years follow-up (based on Denis et al JAMA 2019). Secondary outcomes include incidence of chemotherapy toxicities, patient reported outcomes, and cost effectiveness. Enrollment is anticipated to start in March 2022. A community advisory board of 12 cancer patients and stakeholders meet on a quarterly basis to provide feedback on study activities (e.g., usability testing, adaptations, overall implementation) and ensure the project responds to the needs and preferences of rural cancer patients in Pennsylvania and West Virginia. NIH R01-CA254659. Clinical trial information: NCT05221606.
Olanzapine versus fosaprepitant for prevention of chemotherapy induced nausea and vomiting in patients receiving carboplatin (AUC ≥ 4) containing chemotherapy regimen: A phase 3 randomized, double-blind, placebo-controlled trial.
Authors: Bhargave Sneh , kumar akash , Sharma Vinod , Kataria Babita , Pushpam Deepam , Batra Atul , Pramanik Raja , Khurana Sachin , Sahoo Ranjit Kumar , Malik Prabhat Singh , Bakhshi Sameer , Sharma Atul , Kumar Lalit 
Published: June 2022

TPS12149 Background: Chemotherapy-induced nausea and vomiting (CINV) is a common adverse effect affecting quality of life of patients of cancer undergoing chemotherapy. Carboplatin alone or in combination with various other chemotherapy drugs is one of the most commonly used drug in solid malignancies. It is categorised as a highly emetogenic drug in doses above AUC≥4 and multiple past studies revealed high CINV incidence. Current international antiemetic guidelines suggest NK1 receptor antagonist based triplet drugs as an effective regimen of CINV control in these patients. However, the nausea control rates are largely inadequate. Olanzapine, an atypical antipsychotic drug, is another drug that has shown significant activity in CINV control and is an integral part of current chemotherapy induced emesis and nausea prevention. However, robust comparative studies of olanzapine based triplets with NK1 based combination have been lacking. Hence we planned this study to compare efficacy of olanzapine containing triplet with NK1 receptor antagonist (fosaprepitant) based triplet drug combination in a phase 3 randomised study. Methods: This study is an investigator initiated phase 3 prospective randomised double blind placebo controlled trial comparing efficacy of olanzapine, 5HT3 receptor antagonist(ondansetron) and dexamethasone (experimental arm) against fosaprepitant, 5HT3 receptor antagonist(ondansetron) and dexamethasone (standard arm) for prevention of CINV among chemo-naïve patients (aged ≥18 years) receiving carboplatin (AUC ≥4) based chemotherapy regimen. Primary objective is to compare the number of patients with no nausea during overall periods (0-120 hours post-chemotherapy). Secondary objectives are to compare complete response (no emetic episodes and no use of rescue medication) in the acute(0-24 hr), delayed(25-120 hr),overall periods(0-120 hr) and to assess the frequency of rescue medication use. The other secondary objective includes assessment of adverse events in both the arms. Statistical Design: Planned accrual is total 214 patients including 10% drop out rate. It is a superiority design with an absolute improvement of 20% in the proportion of patients with no nausea from a baseline prevalence of 40% in the standard arm and two sided alpha of 5% as well as power of 80%. Conduct to date :Study activation : March 2021. Enrolment : 138 subjects. Clinical trial information: CTRI/2021/03/032165.
Addressing Latinx CANcer Care Equity (ALCANCE) randomized controlled trial: Precision medicine and community health workers.
Authors: Rodriguez Gladys M. , Wood Emily H. , Leach Maria , Villicana Gerardo , Murillo Ariana , G. Rosas Lisa , Duron Ysabel , O'Brien Dale G. , Koontz Zach , Patel Manali I. 
Published: June 2022

TPS1601 Background: Cancer mortality has declined over the past decade due to clinical advances including precision medicine. Despite these clinical advancements, low-income and racial/ethnic minorities experience worse cancer morbidity and mortality. Specifically, these populations have lower rates of genomic testing and are significantly underrepresented in precision medicine research. Community-based, culturally tailored approaches are needed to address these ongoing disparities. The objective of this randomized controlled trial is to test whether a community health worker (CHW)-led intervention can improve patient understanding of precision medicine topics and delivery of evidence-based cancer care more than usual cancer care alone. Methods: We developed a county-wide cancer care initiative and a community advisory board (CAB) comprised of patient, caregiver, payer, clinician, and governmental stakeholders in Monterey County—comprised of 60% Latinx, non-English speaking, immigrant populations. As guided by the CAB, we developed a CHW-model to provide education on precision medicine and screen for complications of social determinants of health in 1:1 discussions with patients. In collaboration with a local community oncology clinic, we plan to randomize 110 patients with cancer who are receiving active treatment into usual care or usual care plus the CHW-led intervention. Inclusion criteria includes patients who are: 1) 18 years of age or older; 2) racial/ethnic minorities; 3) low-income; 4) uninsured or insured by Medicaid and/or local agricultural employers; and 5) speak English or Spanish. Exclusion criteria includes: 1) lack capacity to consent to study procedures; 2) plan to move from the area within a year. We will measure the effect of the intervention on patient knowledge of precision medicine using a survey adapted from Davies et al. Secondary outcomes include effect on health-related quality of life using the Functional Assessment of Cancer Therapy – General, patient activation using the Patient Activation Measure, satisfaction using the Satisfaction with Decision Scale, prognosis and treatment preferences using an adapted survey by Weeks et al., healthcare utilization, and receipt of evidence-based cancer care. We will administer surveys at baseline, 3-, 6- and 12-months post-enrollment. To date, 67 participants have been enrolled. This study will show if CHW-models increase knowledge of precision medicine in this population. Clinical trial information: NCT04843332.
GBM AGILE: A global, phase 2/3 adaptive platform trial to evaluate multiple regimens in newly diagnosed and recurrent glioblastoma.
Authors: Cloughesy Timothy Francis , Alexander Brian Michael , Berry Donald A. , Colman Howard , de Groot John Frederick , Ellingson Benjamin M. , Gordon Gary B. , Khasraw Mustafa , Lassman Andrew B. , Lee Eudocia Quant , Lim Michael , Mellinghoff Ingo K. , Nelli Apoorva , Perry James R. , Sulman Erik P. , Tanner Kirk , Weller Michael , Wen Patrick Y. , Yung W. K. Alfred ,   GBM AGILE Investigators
Published: June 2022

TPS2078 Background: GBM AGILE (Glioblastoma Adaptive, Global, Innovative Learning Environment) is a biomarker based, multi-arm, international, seamless Phase 2/3 Response Adaptive Randomization platform trial designed to rapidly identify experimental therapies that improve overall survival and confirm efficacious experimental therapies and associated biomarker signatures to support new drug approvals and registration. GBM AGILE is a collaboration between academic investigators, patient organizations and industry to support new drug applications for newly diagnosed and recurrent GBM. With its adaptable structure, GBM AGILE has continued trial activation, inclusion of new investigational therapies, and enrollment globally through the challenges of a global pandemic. Methods: The primary objective of GBM AGILE is to identify therapies that effectively improve the overall survival in patients with ND or recurrent GBM. Bayesian response adaptive randomization is used within subtypes of the disease to assign participants to investigational arms based on their performance. Operating under a Master Protocol, GBM AGILE allows multiple drugs from different pharmaceutical/biotech companies to be evaluated simultaneously and/or over time against a common control. New experimental therapies are added as new information about promising new drugs is identified while other therapies are removed as they complete their evaluation. The master protocol/ trial infrastructure includes efficiencies through an adaptive trial design, shared control arm and operational processes such as risk-based monitoring and enhanced remote activities. GBM AGILE has screened over 1000 patients and enrollment rates are 3 to 4 times greater than traditional GBM trials, with active sites averaging 0.75 to 1 patients/sites/month. While enrollment had an initial dip during the early stages of the pandemic (April-May, 2020), with flexible processes including remote based monitoring, minimizing in person visits, and remote provision of IMP, the enrollment rebounded by June, 2020. Through the use of improved and efficient processes allowed within a master protocol/adaptive platform trial infrastructure, GBM AGILE has been seamlessly operating a global trial during a global pandemic. Clinical trial information: NCT03970447.
Design and initiation of an adaptive, randomized, controlled study of berubicin, a topoisomerase 2 poison that crosses the blood brain barrier (BBB), for the treatment of recurrent glioblastoma multiforme (GBM) after first-line therapy.
Authors: Silberman Sandra , Hsu Sigmund H. , Muzyczenko Zena , Picker Donald , Priebe Waldemar 
Published: June 2022

TPS2083 Background: Berubicin (also known as WP744) is a patented doxorubicin (Dox) analog with evidence that it crosses the BBB and has significant central nervous system (CNS) uptake. Induction of apoptosis and DNA damage by Berubicin was compared with Dox and showed much greater potency of Berubicin in all tested cancer cells, also significantly and consistently showing higher cytotoxicity than Dox. In models of intracranial orthotopic gliomas, Berubicin prolonged survival when compared to temozolomide, currently a standard of care in GBM. Evaluation of these models also showed that Berubicin had greater infiltration into the tumor compared to normal tissue, providing additional justification for its observed improved efficacy. Based on this data, a Phase 1 dose escalation study was conducted in patients with recurrent primary brain tumors. Berubicin was well tolerated, with myelosuppression (neutropenia and thrombocytopenia) as dose-limiting toxicities. Of 25 patients evaluable for efficacy, there was 1 complete response (14+ years), 1 partial response durable for 12 weeks, and 9 patients with stable disease over 6 weeks for a clinical benefit rate of 44%. Methods: CNS Pharmaceuticals, Inc. (“CNSP”) has licensed Berubicin and initiated a randomized, controlled clinical trial of Berubicin vs. Lomustine in adults with recurrent GBM after first line therapy. The primary endpoint of this study, being conducted in the United States and Europe, is overall survival (OS), with a projected 243 patients enrolled in a 2:1 randomization design (Berubicin:Lomustine). This study has pharmacokinetic (PK) evaluations of all patients enrolled, with at least 15 patients undergoing complete PK assessments throughout the initial dosing period (3 days of IV administration of Berubicin over 2 hours, repeated every 3 weeks). Patients will be stratified on the basis of MGMT methylation, there will be documentation of IDH WT status, and no prior administration of bevacizumab will be allowed. An interim analysis will evaluate the comparative effectiveness of these treatments, an adaptive design intended to demonstrate that Berubicin’s efficacy is at least equal to that of Lomustine such that continuation of the study is in patients' best interests (futility analysis). The overall survival endpoint and sample size have been calculated to be able to show a statistical difference between the two therapies as second line treatment for GBM. Additional studies in malignant diseases of the CNS (e.g., pediatric brain tumors, primary CNS lymphoma, metastatic tumors) are also being explored based on the potential for anthracycline activity in these indications. For the present study posted on clinicaltrials.gov as, additional details and contact information is available. Clinical trial information: NCT04762069.
A phase 1, first-in-human (FIH) study of adenovirally transduced autologous macrophages engineered to contain an anti-HER2 chimeric antigen receptor (CAR) in participants with HER2 overexpressing solid tumors.
Authors: Reiss Kim Anna , Yuan Yuan , Ueno Naoto T. , Johnson Melissa Lynne , Gill Saar , Dees Elizabeth Claire , Chao Joseph , Angelos Mathew , Shestova Olga , Serody Jonathan Stuart , Priceman Saul , Barton Debora , Swaby Ramona F. , Ronczka Amy , Condamine Thomas , Cushing Daniel , Qureshi Rehman , Kremp Madison , Klichinsky Michael , Abdou Yara 
Published: June 2022

TPS2677 Background: Adoptive T cell therapies have led to remarkable advances among patients with hematologic malignancies, but have had less success in those with solid tumors. Macrophages are actively recruited and abundantly present in the solid tumor microenvironment (sTME). Tumor associated macrophages are predominantly immunosuppressive and support tumor growth (M2), while a subset of proinflammatory macrophages enhance anti-tumor immunogenicity (M1). M1 macrophage function can be augmented by CAR expression to selectively recognize and phagocytose antigen overexpressing cancer cells. Moreover, CAR macrophages can reprogram the sTME and present neoantigens to T cells, leading to epitope spreading and anti-tumor immune memory. Human Epidermal Growth Factor Receptor 2 (HER2) overexpression promotes tumorigenesis in many solid tumors (Table). CT-0508 is a cell product comprised of autologous monocyte-derived proinflammatory macrophages expressing an anti-HER2 CAR. Pre-clinical studies have shown that CT-0508 induced targeted cancer cell phagocytosis while sparing normal cells, decreased tumor burden, prolonged survival, and were safe and effective in a semi-immunocompetent mouse model of human HER2 overexpressing ovarian cancer. Methods: This Phase 1, FIH study is evaluating safety, tolerability, cell manufacturing feasibility, trafficking, and preliminary evidence of efficacy of investigational product CT-0508 in 18 participants (pt) with locally advanced (unresectable) or metastatic solid tumors overexpressing HER2. Pt previously treated with available therapies, including anti-HER2 therapies, as indicated, and subsequent progression are permitted. Filgrastim is used to mobilize autologous hematopoietic progenitor cells for monocyte collection by apheresis. CT-0508 is manufactured, prepared, and cryopreserved from mobilized peripheral blood monocytes. Group 1 pt (n=9) receive CT-0508 infusion split over D1, 3, and 5. A Safety Review Committee will review dose limiting toxicities. Group 2 pt (n=9) will receive the full CT-0508 infusion on D1. Pre- and post-treatment biopsies and blood samples will be collected to investigate correlates of safety (immunogenicity), trafficking (RNA scope), CT-0508 persistence in blood and in the tumor, target antigen engagement, TME modulation (single cell RNA sequencing), immune response (TCR sequencing) and others. Radiographic imaging is also being conducted to assess preliminary tumor activity. Clinical trial information: NCT04660929. [Table: see text]
Design and rationale of a phase 1 dose-escalation study of AMG 193, a methylthioadenosine (MTA)-cooperative PRMT5 inhibitor, in patients with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors.
Authors: Villalona-Calero Miguel Angel , Patnaik Amita , Maki Robert G , O'Neil Bert , Abbruzzese James L. , Dagogo-Jack Ibiayi , Devarakonda Siddhartha , Wahlroos Sara , Lin Chia-Chi , Fujiwara Yutaka , Terbuch Angelika , Postel-Vinay Sophie , Goebeler Maria-Elisabeth , Addeo Alfredo , Prenen Hans , Arkenau Tobias , Sacher Adrian G. , Liu Chunxu , Kormany William , Rodon Ahnert Jordi 
Published: June 2022

TPS3167 Background: Protein arginine methyltransferase 5 (PRMT5) is an emerging target for cancer treatment. MTAP homozygous deletion occurs in 15% of cancers and often coincides with deletion of the tumor suppressor gene CDKN2A, leading to buildup of its substrate MTA. MTA shares close structural similarity to S-adenosyl methionine (SAM), the substrate methyl donor for PRMT5. By competing with SAM, MTA partially inhibits PRMT5. Thus, MTAP-null cancers are susceptible to further PRMT5 inhibition (Kryukov Science 2016). Current direct/indirect PRMT5 inhibitors (PRMT5i) showed preliminary anticancer activity, albeit with considerable toxicities due to their indiscriminate activities. AMG 193 is an MTA-cooperative PRMT5i that preferentially targets the MTA-bound state of PRMT5 that is enriched in MTAP-null tumors and represents a novel strategy to increase the therapeutic margin of this class of inhibitors. AMG 193 potently inhibits MTAP-null cancer cell lines and patient-derived xenografts. Methods: NCT05094336 is a first-in-human (FIH), multicenter, open-label, phase 1/1b/2 trial evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and efficacy of AMG 193 in patients with advanced MTAP-null solid tumors. Eligible patients (≥ 18 years) with histologically confirmed locally advanced/metastatic solid tumors not amenable to curative treatment with surgery and/or radiation, homozygous MTAP and/or CDKN2A deletion (by local next generation sequencing), or MTAP protein loss in tumors (by central immunohistochemistry), measurable disease, ECOG PS 0‒1, adequate hematopoietic, renal, liver, pulmonary, cardiac, coagulation function and glucose control will be included. The study will be conducted in 3 parts, each with subparts. Here, we describe Part 1a/b (dose exploration). Five dose levels are planned. Treatment continues until progression or withdrawal. The primary objectives are to evaluate the safety and tolerability of AMG 193 monotherapy; endpoints include dose-limiting toxicities, treatment-emergent adverse events, serious adverse events, electrocardiograms, laboratory abnormalities, and vital signs. Secondary objectives include the characterization of the PK parameters of AMG 193 including Cmax, Tmax, and AUC after single or multiple doses. This study is expected to enroll approximately 30 patients in Part 1a/b. This is the first FIH trial open for enrollment for this new class of PRMT5i and enrollment is ongoing. Clinical trial information: NCT05094336.
CoRInTH: A phase Ib/II trial of checkpoint inhibitor, pembrolizumab (PD-1 antibody [Ab]) plus standard intensity modulated chemoradiotherapy (IMCRT) in HPV-induced stage III squamous cell carcinoma (SCC) of the anus.
Authors: Hall Marcia , Adams Richard , Guren Marianne Grønlie , Carucci Margherita , Nixon Lisette , Porter Catharine , Bhuva Neel , Glynne-Jones Robert , Harrison Mark ,   CoRInTH Trials Group
Published: June 2022

TPS3630 Background: SCC of anus (SCCA) are considered rare tumours, but the incidence is increasing. Only 65% patients with later stage T3/T4 +/-N1 SCCA remain disease free at 3 years (Gunderson 2013, James 2013). The cytotoxicity of IMCRT enhances tumour antigen presentation and promotes cytokine release as well as enhancing the MHC (Demaria 2004, Reits 2006). Immune therapy, against PD-1, have been approved for patients with SCC arising from other primary sites eg. head and neck, lung cancer. The addition of such checkpoint inhibitors might also result in improved PFS and OS for higher risk SCCA patients. Methods: A multicentre, single arm, open-label, non-randomised study to evaluate the safety and tolerability of different schedules of exposure to pembrolizumab (P) with standard IMCRT in 50 patients with locally advanced T3/4 anal cancer. The first cohort of 6 patients commenced standard IMCRT and received P 200mg every 21d beginning at Week 5 day 1 of the IMCRT schedule. If this is considered safe and tolerable with not more than 3/6 SAEs within first 6 weeks after completion IMCRT, a second cohort of 6 patients will be recruited where P is introduced on Week 1 Day 1 with standard IMCRT. Pembrolizumab monotherapy will be continued for a total of 6 months. Primary endpoint is safety and tolerability by assessing AEs and protocol adherence. Secondary endpoints include feasibility, clinical response assessment by RECIST (MRI) for ORR at 3, 6 and 12 months, imaging response assessments by TRG MRI using changes in Apparent Diffusion Coefficient (ADC) on diffusion weighted sequences and patient reported outcomes, using EORTC quality of life questionnaires. Patients are being asked to contribute to translational endpoints with the donation of tissue and blood samples. Eligible patients will have Stage IIIA/B (T3/4, any N, M0) SCCA, performance status 0 or 1 and be suitable for IMCRT. Patents with anal tumours of non-epithelial origin, metastatic disease or a diagnosis of immunodeficiency are excluded. Single phase IMRT with a simultaneous integrated boost to achieve 53.2Gy in 28 fractions over 5.5 weeks to PTV_A, according to the UK consensus is mandated. Concomitant chemotherapy can either be cisplatin 60mg/m2/ or mitomycin 12mg/m2 with either 5FU 1000mg/m2 or capecitabine 825mg/m2 at investigator discretion. The first cohort has completed recruitment with Safety Review Committee / IDMC review planned for April 2022. Patients will then be sought to start P on Week 1 Day 1 with IMCRT. Further safety review will be undertaken following the first 6 patients entered into the second cohort but recruitment will continue in an expansion phase to a maximum of 44 patients. Clinical trial information: NCT04046133.