bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ARETHA study: A phase 2 randomized control trial of eribulin with evexomostat (SDX-7320) or placebo for patients with metastatic triple-negative breast cancer (TNBC) and metabolic dysfunction.
Authors: Shen Sherry , Solomon Verna , Williams Dominiq , Robson Mark E. , Norton Larry , Traina Tiffany A. , Iyengar Neil M. 
Published: June 2023

TPS1131 Background: The prognosis for advanced/metastatic TNBC remains poor and novel therapeutic strategies are urgently needed. Insulin resistance and obesity contribute to TNBC progression and are independent predictors of worse survival. Methionine aminopeptidase 2 (MetAP2/p67) is overexpressed in many tumor types including breast. MetAP2 inhibitors exhibit broad anti-tumor activity and attenuate the effects of metabolic dysfunction on tumor growth. Evexomostat (SDX-7320) is a second-generation MetAP2 inhibitor that improved insulin sensitivity, reduced fat mass, and normalized adipokine levels in preclinical models of obesity and reduced tumor growth in TNBC preclinical models. In phase 1 trials, evexomostat monotherapy partially restored insulin sensitivity, reduced adipokines, and showed anti-metastatic effects in patients with advanced solid tumors. The goal of this phase 2 study is to test whether evexomostat prevents worsening of insulin resistance and augments tumor response in patients with metastatic TNBC and metabolic dysfunction in combination with eribulin chemotherapy, a standard of care treatment option after prior anthracycline and taxane exposure. Methods: This is a single-center phase 2 randomized control trial of evexomostat, a MetAP2 inhibitor, and eribulin chemotherapy. Key eligibility criteria include metastatic TNBC, measurable disease or ≥1 predominantly lytic bone lesion, baseline hemoglobin A1c >5.5% and/or BMI ≥30 kg/m2, and ≤2 prior lines of therapy in the advanced/metastatic setting. Patients with uncontrolled or insulin-dependent type II diabetes, or who require combination antihyperglycemic therapy are excluded. During the safety run-in period, 15 patients will be assigned to receive evexomostat 49 mg/m2 Q2 weeks and eribulin 1.4 mg/m2 on days 1 & 8 of a 21-day cycle. Upon safety confirmation, an additional 40 patients will be randomized 2:1 to receive evexomostat or placebo with eribulin. The primary endpoint is metabolic efficacy assessed by change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score. Secondary endpoints include objective response rate, progression-free survival, safety and tolerability, patient-reported outcomes, and changes in metabolic markers and body composition. Historically, HOMA-IR scores double during chemotherapy, and this trial will test whether evexomostat attenuates the expected HOMA-IR rise. This trial will have >90% power to detect a difference between a 1.5-fold change in HOMA-IR in the control arm vs. no change in the evexomostat arm while controlling the Type I error at 5%. As of Feb 2022, 3 patients are enrolled; total accrual of 61 patients is planned with a goal of 55 evaluable patients. Clinical trial information: NCT05570253 .
Comprehensive 0utcomes for After Cancer Health: COACH.
Authors: Lally Robin Mary , Schmidt Rachael , Tlusty Gisele , Jackson Mariah Kay , Arthur Elizabeth , Barr Austin , Flora Laura , Hammer Marilyn J. , Jones Jessica Trevino , Lynch Kelly Debra , Krok-Schoen Jessica L. , Loftis Jennifer , Saligan Leorey , Starkweather Angela , Vazquez Michael , Whisenant Meagan , Wright Alexi A. , Brassil Kelly Jean 
Published: June 2023

TPS12141 Background: The landscape for cancer survivors continues to evolve as individuals live longer following primary therapy. For some, treatment is complete; for others, active surveillance or maintenance therapy may be indicated. Individual survivorship needs are diverse, influenced by tumor and treatment type, as well as social determinants of health. Digital interventions may support survivors in achieving personalized health goals throughout survivorship. The Comprehensive Outcomes for After Cancer Health (COACH) Study (NCT05349227) explores the feasibility of a digital health coaching (DHC) program for individuals enrolled with diverse tumor types and geographic regions. Methods: COACH is a multi-center, randomized, wait-list control trial enrolling 550 individuals ≥18 years old who are within 1-year of completion of primary cancer therapy at enrollment. Up to 100 participants, will be recruited at each of 6 study sites, of which 3 are currently enrolling. Consented individuals are randomized to 6 months of DHC or 6 months of data collection only, then cross-over for follow-up to 12-months. Both groups wear an activity tracker; complete patient reported outcome measures; and provide fecal specimens. The DHC program includes weekly Health Advisor calls and supplemental delivery of evidenced-based content via text, email or mobile platform. Topics fall in health domains of physical, mental/emotional, financial, social, and sexual, and emphasize nutrition, physical activity, sleep, and screening for recurrent or de novo cancer. Feasibility for this study is defined as a retention rate greater than or equal to 70%, and acceptability will be defined as less than or equal to 20% scoring “not at all helpful.” Trends over time will be assessed using linear mixed models using time as a fixed effect, as well as any covariates and interactions of interest. Descriptive statistics will be used to evaluate exploratory endpoints. A cross-cohort end-point related to physical function as measured by the PROMIS Physical Function 10a, will also be evaluated. To date, 72 individuals have enrolled, with Nebraska as the lead site, including 71 women, with a mean age of 61.78 (Range 33-74), from the U.S. Midwest (n = 57) and Northeast (n = 15). 4 identify as African American/Black, 68 as White. 50 have a breast, 13 ovarian, 8 endometrial, 1 gastric diagnosis. Nine have completed the first 6 months of the study. The study is novel in the breadth of data collected and potential to understand variability in patient experiences and provide insights into the feasibility, acceptability, and efficacy of a DHC intervention supporting individuals after primary cancer treatment. Clinical trial information: NCT05349227 .
Empathic communication skills training: Randomized controlled trial to reduce lung cancer stigma in lung cancer care.
Authors: Ostroff Jamie S. , King Jennifer C. , Ciupek Andrew , Nichols Brittney , Malling Charlotte , Rosenthal Lauren , Banerjee Smita C. 
Published: June 2023

TPS12152 Background: Stigma is commonly experienced by people diagnosed with lung cancer and is often triggered during clinical encounters with their oncology care provider (OCP), particularly associated with routine assessment of smoking history. Lung cancer stigma is associated with gaps in quality of care as well as poorer psychological and physical health-related outcomes for patients. The overall objective of this multi-site national clinical trial is to test whether an OCP-facing training intervention in empathic communication skills (ECS) reduces stigma and distress and promotes patient engagement. Our prior pilot work has demonstrated that the ECS intervention is both feasible and efficacious to reduce stigma during clinical encounters. Methods: This NCI-funded multi-site national trial employs a cluster randomized design comparing usual care (waitlist control) with ECS training (intervention). With outreach and site recruitment support provided by GO2 for Lung Cancer and the American Cancer Society, community oncology sites (n = 16) nationwide will be randomized 1:1 to each arm. 9-11 OCPs will be recruited per site with 6 unique patients per OCP enrolled (total 54-66 patients/site). Statistical analysis will evaluate the effect of ECS training on primary OCP outcomes (e.g., empathic skill uptake) and secondary patient-reported outcomes (e.g., psychological distress). The 2.5 hour ECS training is delivered live using a videoconference platform. The didactic content covers knowledge and consequences of stigma on patients with lung cancer and in-depth review of specific ECS strategies. Participants then engage in experiential small-group role-play sessions with trained patient actors, where they are given tailored feedback by trained facilitators and their peers. Eligible sites must have at least 15 OCPs and clinic volume of at least 20 new patients with lung cancer per month. Eligible OCPs (physicians, NPs and PAs) must currently be treating and conducting outpatient clinic consultations with at least 1 patient with lung cancer per week. Eligible patients must be receiving treatment for lung cancer, English and/or Spanish speaking, currently or formerly smoking, and have had no more than 5 prior visits with the participating OCP. Currently, this trial is open to accrual and has 5 sites across the nation completing paperwork for activation. Clinical trial information: NCT05456841 .
Mixed-methods clinical trial to evaluate the feasibility of the CURATE.AI optimised digital cognitive rehabilitation therapeutic (COR-Tx) in patients post brain radiotherapy.
Authors: Raczkowska Marlena N. , Remus Alexandria , Vijayakumar Smrithi , Kwek Siong Peng , Lee V Vien , Tadeo Xavier , Ng Grady , Lau Ni Yin , Leong Qiao Ying , Chai Qian Yee , Aliyah Fatin , Blasiak Agata , Chia Wei Tsau David , Asplund Christopher L. , Ho Dean , Vellayappan Balamurugan A. 
Published: June 2023

TPS1615 Background: Cognitive decline may be exacerbated, in brain tumour patients, by prior radiotherapy (RT). Traditional interventions to mitigate this typically involve fixed dose or intensity pharmacological and/or cognitive rehabilitation therapies that often elicit sub-optimal or no response, due to the dynamically evolving patient state and low adherence. Personalised digital therapeutics (DTx) may be more effective for this population. Further, gamification has previously shown to induce positive health behavioural change and improve intervention adherence. To this end, we have developed the CURATE.AI COR-Tx platform, a gamified DTx, that combines a previously validated, small-data artificial intelligence-derived dose optimisation technology with digital multitasking cognitive training. This novel DTx dynamically personalises treatment by using the patient’s own longitudinal performance data to generate an evolving digital avatar that guides training intensity throughout the intervention. Herein, we aim to evaluate feasibility, user experience and usability of the DTx platform in brain tumour patients post-RT. Methods: This is a prospective, mixed-methods, interventional, single-arm, decentralised feasibility clinical trial. The primary objective is to evaluate feasibility of the CURATE.AI COR-Tx platform as both a digital intervention (DI) and digital diagnostic (DD) for cognitive function in 15 patients with brain tumour post-RT. The personalised and home-based DI involves completing three 12-min sessions per week for 10 weeks, starting 1 month post-RT. Cognitive function will be assessed via a combined non-digital cognitive evaluation and a DD session at five time points: prior to RT, pre- & post-DI and 16- and 32-weeks post-DI. Feasibility outcomes relating to acceptability, demand, implementation, practicality and limited efficacy testing and additional secondary and exploratory outcomes relating to usability and user experience will be collected by the clinical team and through semi-structured patient interviews and a study team focus group discussion at study completion. We will adopt a mixed-methods approach for data analysis. Feasibility of the CURATE.AI COR-Tx platform will be evaluated through thematic analysis for qualitative outcomes (acceptability and practicality), and descriptive and correlational analysis for quantitative outcomes (demand and implementation). We will adopt the CONSORT traffic light system to decide on future expansion into a large-scale randomised control trial. This trial began in April 2021 and has enrolled 14 of planned 15 patients at the time of submission. Clinical trial information: NCT04848935 .
A first-in-human study of XTX301, a masked, tumor-activated interleukin-12 (IL-12), in patients with advanced solid tumors.
Authors: Knecht John George , Gupta Anurag , Duncan Meghan , Crowe David , Patel Ekta , O'Neil Jennifer , Lee George , Luptakova Katarina , Gutierrez Martin 
Published: June 2023

TPS2672 Background: Interleukin-12 (IL-12) is a proinflammatory cytokine that has shown promise as an immunotherapy for cancer. Although it has demonstrated potent antitumor activity in mouse models of cancer, development of IL-12 in the clinical setting has been limited by severe toxicities with systemic administration. XTX301 is a half-life extended, masked and tumor-activated IL-12. XTX301 is designed to be pharmacologically inactive in non-tumor tissue when circulating systemically, and unmasked by matrix metalloproteases (MMPs) preferentially active in the tumor microenvironment (TME). The masking domain is engineered to be removed via cleavage at a protease cleavage site in the XTX301 linker by MMPs. XTX301 is designed to produce a localized anti-tumor immune response while limiting exposure of the active form of XTX301 in non-tumor tissue, and thereby improving the therapeutic index of IL-12. Using a murine analog of XTX301 (mXTX301), tumor growth inhibition was demonstrated in vivo in murine models with a single dose of mXTX301. In mouse tumors, mXTX301 stimulated the infiltration of cytotoxic CD8+ T cells and induced pro-inflammatory gene expression signatures. Preclinical data have demonstrated tumor-selective activity of mXTX301 in mice with limited and reversible peripheral toxicities of XTX301 in non-human primates [Malkova et al., AACR 2023]; these data are supportive of further clinical development. Methods: XTX301-01 trial (NCT05684965) is a first-in human, multicenter, Phase 1, open label study to establish the safety and tolerability of monotherapy XTX301, and to determine a recommended phase 2 dose (RP2D). Additional objectives include assessment of pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity and anti-tumor activity of XTX301. The study will enroll patients with solid tumors, including lymphoma, that have locally advanced or metastatic disease and have failed standard therapy, standard therapy does not confer survival benefit, or standard therapy is not available. Patients in part 1A will receive XTX301 monotherapy every 3 weeks via intravenous infusion in an outpatient setting, using a 3+3 dose escalation design. The starting dose for XTX301 is 5 ug/kg. Part 1B will further examine multiple doses of XTX301 as monotherapy in patients with select advanced solid tumors to further characterize PK, PD and dose response relationships. Part 1B will require mandatory fresh tumor biopsies before and after initiation of study drug administration to fully characterize the PD profile and PK of XTX301 in the tumor. Enrollment to the study is planned to begin in the first quarter of 2023. Clinical trial information: NCT05684965 .
A prospective observational study investigating the impact of immune checkpoint inhibitors for cancer on fertility in males and females of child-bearing age (immuno-fertility).
Authors: Keogh Rachel J , O'Reilly David , Marks Sam Jonathan , Horan Maebh , Elebert Rachel , Glover Louise , Milewski Maciej , Egan Keith , Hennessy Bryan T , Grogan William , Morris Patrick G. , Breathnach Oscar S. , Murphy Adrian Gerard , Wingfield Mary , Crosby David A , Naidoo Jarushka 
Published: June 2023

TPS2679 Background: Anti-PD-1/PD-L1/CTLA4 agents have revolutionized the treatment landscape of many cancer types, resulting in durable responses. With recent approvals in the adjuvant setting, the long-term consequences of immune checkpoint inhibitors (ICIs) such as the impact on fertility are of increasing clinical relevance. The impact of ICI therapy on fertility is poorly understood. Based on published data, we hypothesize that patient fertility may be affected by ICIs via several mechanisms, including: endocrine dysfunction, direct impact on gametogenesis, or autoantibody formation. Methods: We designeda prospective, multi-center translational study that aims to identify the effects of ICIs on fertility. We aim to recruit 88 patients over 3-4 years. Participants of child-bearing age as defined by study protocol who are due to start ICIs for any solid tumour malignancy, will be eligible. The primary endpoint of the study is a change in anti-Müllerian hormone level and antral follicle count in females, and a change in sperm concentration, motility, morphology in males measured before and serially during ICI therapy (up to 24 months). Secondary endpoints include analysis of FSH, LH, testosterone levels, the proportion of patients with a persistent change in any one reproductive parameter as assessed at follow-up visits, frequency of oligo/amenorrhoea in females and immunologic changes in seminal fluid in males. Conclusions: ICIs have led to a significant improvement in the long-term survival in selected patients with cancer. This study will elucidate the effects of ICIs on both male and female fertility over time, and provide useful information to guide patients and their care teams regarding long-term effects of ICIs on fertility. Recruitment is ongoing.
TROPION-Lung04: Phase 1b, multicenter study of datopotamab deruxtecan (Dato-DXd) in combination with immunotherapy ± carboplatin in advanced/metastatic non-small cell lung cancer (mNSCLC).
Authors: Borghaei Hossein , Waqar Saiama Naheed , Bruno Debora S. , Kitazono Satoru , Wakuda Kazushige , Spira Alexander I. , Olivares Jairo , Mak Gabriel , Lovick Susan , Goodwin Louise , Papadopoulos Kyriakos P. 
Published: June 2023

TPS3158 Background: Datopotamab deruxtecan (Dato-DXd) is a TROP2-directed antibody drug conjugate that has shown encouraging preliminary activity and safety in patients (pts) with lung or breast cancers. The TROPION-Lung04 study was designed to assess the safety, tolerability, and antitumor activity of Dato-DXd in combination with immunotherapy ± carboplatin in pts with advanced or metastatic NSCLC. Methods: TROPION-Lung04 (NCT04612751) is a Phase 1b, multicenter, open-label, 2-part, dose escalation/confirmation and expansion study in ≈232 pts without actionable genomic alterations. In Part 1 (dose escalation/confirmation), pts will be enrolled to 1 of up to 11 cohorts. Details of cohorts 1–4 (Dato-DXd [4 or 6 mg/kg] + durvalumab [1120 mg Q3W] ± up to 4 cycles of carboplatin [AUC 5] Q3W) were previously described (Borghaei H, et al. JTO 2021;16(10):S1098-S1099). Cohorts 5–11 were recently added to evaluate Dato-DXd in combination with bispecific immunotherapies AZD2936 (anti-PD-1/TIGIT) and MEDI5752 (anti-PD-1/CTLA-4) in treatment-naïve pts. Pts in cohorts 5–8 will receive Dato-DXd (4 or 6 mg/kg) + AZD2936 ± carboplatin; pts in cohorts 9–11 will receive Dato-DXd + MEDI5752 ± carboplatin. Cohorts 5 and 6 will recruit pts with PD-L1 tumor proportion score (TPS) ≥50% in Parts 1 and 2A, and PD-L1 TPS 1–49% in Part 2B. Cohorts 7–11 will recruit pts with PD-L1 TPS < 50% only. Dose confirmation in Cohorts 5–11 will be guided by an mTPI-2 design where a minimum of 6 and a maximum of 9 pts will be assessed for dose-limiting toxicities (DLTs) during Cycle 1; if the DLT incidence meets prespecified toxicity criteria, Part 2 dose expansions may be opened. Pts may continue Dato-DXd or immunotherapy treatment until disease progression (per RECIST v1.1) or unacceptable toxicity. Study endpoints are shown in the table. Enrolment across all combination cohorts is ongoing. Clinical trial information: NCT04612751 . [Table: see text]
First-in-human clinical trial design of a first-in-class theranostic approach with a peptide-based radioligand targeting CA IX-expressing tumors.
Authors: Feldman Darren R. , Tran Ben , Emmett Louise , Hofman Michael S , Olivier Pierre , Mahammedi Hakim , Galetic Ivana , Pokorska-Bocci Anna , Bouisset Florilene , Gollmer Kathrin , Pavlyuk Mariya , Tauchmanova Libuse , Herrmann Ken 
Published: June 2023

TPS3160 Background: Expression of carbonic anhydrase IX (CA IX), a cell surface glycoprotein, can be induced by a state of hypoxia or by mutation of the Von Hippel-Lindau tumor suppressor gene. CAIX expression in tumors is often associated with progressive disease and overall poor outcomes in various solid cancers. Notably, high CA IX expression has been observed in 83%, 40%, and 29% of clear cell renal cell carcinoma (ccRCC), pancreatic ductal adenocarcinoma (PDAC), and colorectal cancer (CRC) specimens, respectively1. CA IX may therefore represent a valuable therapeutic target. DPI-4452 is a first-in-class cyclic peptide that binds with high affinity to CA IX. Radiolabeling DPI-4452 with gallium-68 ([68Ga]Ga-DPI-4452) or lutetium-177 ([177Lu]Lu-DPI-4452) is an innovative theranostic approach for identifying and treating patients (pts) with CA IX-expressing tumors. Pre-clinical data has shown that [177Lu]Lu-DPI-4452 is taken up by tumors and induces dose-dependent growth inhibition in ccRCC and CRC xenograft mouse models1,2. Methods: We present the design of a Phase I/II study (NCT05706129) of [68Ga]Ga-DPI-4452 and [177Lu]Lu-DPI-4452 in pts with unresectable locally advanced or metastatic ccRCC, CRC or PDAC. The study is comprised of three phases: imaging (Part A), dose-escalation (Part B), and expansion (Part C). In Part A, pts will receive a single intravenous (IV) 185 MBq dose of [68Ga]Ga-DPI-4452. Safety, tolerability, pharmacokinetics (PK), dosimetry and imaging characteristics of [68Ga]Ga-DPI-4452 will be evaluated using positron emission tomography/computed tomography (CT) at four timepoints on Day 1. All pts will be followed for seven days post-injection for safety observations. In Part B, based on [68Ga]Ga-DPI-4452 uptake, pts will receive sequential, escalating doses of IV [177Lu]Lu-DPI-4452 on Day 1 of each 28-day cycle for up to eight cycles. During Cycle 1, each pt will undergo up to four whole-body planar imaging and single photon emission CT/CT analyses for dosimetry over seven days. In Part B, the recommended Phase 2 dose of [177Lu]Lu-DPI-4452 will be determined, guided by a Bayesian Logistic Regression model. Safety, PK, and dosimetry will be assessed to minimize any radiation-induced toxicity and to optimize absorbed radiation dose in the tumor. Upon completion of Part B, Part C will enroll up to three cohorts of pts with CA IX-positive ccRCC, CRC or PDAC to assess preliminary efficacy of [177Lu]Lu-DPI-4452, with a primary endpoint of objective response rate, as measured by RECIST v1.1. References Wiedemann N et al. J Nucl Med 2022;63(Suppl 2):4048. Attinger A et al. Eur J Nucl Med Mol Imaging 2022;49(Suppl 1):S1–S751. Clinical trial information: NCT05706129 .