bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 2 randomized study of magrolimab combination therapy in adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): ELEVATE-TNBC.
Authors: Rainey Natalie , Joshi Rohit , Chiu Joanne , Chen Ann , Wang Hao , Odegard Jared , Lopez Rodrigo Estibaliz , Adams Sylvia 
Published: June 2023

TPS1130 Background: Improving outcomes in patients (pts) with TNBC remains a high unmet need. Immune checkpoint inhibitors (ICIs) + chemotherapy (chemo) is approved for newly diagnosed pts with PD-L1+ tumors. Further, single-agent sacituzumab govitecan (SG), a Trop-2–directed antibody-drug conjugate, is approved for pts with mTNBC who received ≥2 prior systemic therapies (≥1 for metastatic disease). However, more options are needed for pts with PD-L1–negative mTNBC and for those with disease progression on chemo ± ICI. Magrolimab is a monoclonal antibody that blocks CD47, a “don’t eat me” signal often overexpressed on TNBC cells. Magrolimab blockade of CD47 induces macrophage-mediated phagocytosis of tumor cells and has shown preclinical activity and promising clinical efficacy in hematologic malignancies. Certain chemos, including taxanes, enhance prophagocytic signals on tumor cells, which may lead to synergistic antitumor activity with magrolimab. This study is evaluating the safety, tolerability, and efficacy of magrolimab + nab-paclitaxel/paclitaxel or + SG in mTNBC. Methods: This open-label study has 2 cohorts (C) with safety run-in and phase (ph) 2 portions. Eligible pts are ≥18 y with measurable disease per RECIST 1.1. C1 pts have PD-L1–negative untreated mTNBC. C2 pts have mTNBC and received 1 prior line of therapy in the advanced setting, a taxane in the neoadjuvant/adjuvant or metastatic setting, and, if PD-L1+, an ICI. Exclusion criteria include active central nervous system disease, RBC transfusion dependence, and prior treatment with CD47/SIRPα-targeting agents. C1 assesses nab-paclitaxel/paclitaxel + magrolimab (safety run-in) or ± magrolimab (ph 2; randomized 1:1). C2 assesses magrolimab + SG (safety run-in and ph 2). In C1 safety run-in, magrolimab is given intravenously (IV) as a 1-mg/kg priming dose on day (D) 1 of cycle 1 to mitigate on-target anemia, followed by 30 mg/kg (cycle 1: D8, 15, 22; cycle 2: D1, 8, 15, 22; cycle 3+: D1, 15) (28-d cycles). In C2 safety run-in, pts receive a 1-mg/kg priming dose on D1, followed by 30 mg/kg (cycle 1: D8, 15; cycle 2: D1, 8, 15) and 60 mg/kg (cycle 3+: D1) (21-d cycles). The recommended ph 2 dose (RP2D) is determined in the safety run-in, with de-escalation if prespecified dose-limiting toxicity (DLT) criteria are met. Once RP2D is determined, the ph 2 cohorts will follow their respective dose schedules. Nab-paclitaxel/paclitaxel and SG are given IV per standard of care. The primary endpoints are incidence of DLTs, adverse events, and abnormal lab results by CTCAE v5.0 (safety run-in); progression-free survival by RECIST 1.1 (ph 2 C1); and confirmed objective response rate by RECIST 1.1 (C2; pooled safety run-in and ph 2). Planned enrollment is ≈144 pts. Clinical trial information: NCT04958785 .
Alliance A092104: A randomized phase 2/3 study of olaparib plus temozolomide versus investigator’s choice for the treatment of patients with advanced uterine leiomyosarcoma after progression on prior chemotherapy.
Authors: Lacuna Kristine Peregrino , Mandrekar Sumithra J. , Allred Jacob B. , Berg Stephanie A. , Hensley Martee Leigh , Van Tine Brian Andrew , George Suzanne , Schwartz Gary K. , Ingham Matthew 
Published: June 2023

TPS11584 Background: Uterine leiomyosarcoma (uLMS) is an aggressive sarcoma subtype with frequent metastatic relapse. Advanced uLMS is treated with gemcitabine/docetaxel or anthracycline-based regimens. After failure of initial chemotherapy, remaining options provide limited benefit (trabectedin: objective response rate (ORR) 11%, median progression-free survival (mPFS) 4.0 months (mo); pazopanib: ORR 11%, mPFS 3.0 mo; dacarbazine: ORR 9%, mPFS 1.5 mo). 18-23% of uLMS harbor deleterious alterations in homologous recombination (HR) DNA repair genes. HR-deficient cancers are unable to effectively repair double-stranded DNA breaks and may be sensitive to poly ADP-ribose polymerase (PARP) inhibitor-based strategies. In preclinical studies, the combination of temozolomide (T), an alkylating agent, and olaparib (O), a PARP inhibitor, markedly suppressed proliferation of uLMS models. Among 22 uLMS patients with median 3 prior lines, O+T demonstrated mPFS 6.9 mo and ORR 27% (Ingham M. et al. ASCO 2021: #11506). In correlative analysis, alterations in HR genes including PALB2 and RAD51B or absence of RAD51 foci formation by a functional assay were observed in patients with prolonged PFS (Bose S. et al. ASCO 2022: #11509). Based on these results, we designed a randomized phase 2/3 study to further evaluate O+T in advanced, pretreated uLMS. Methods: Alliance for Clinical Trials in Oncology A092104 is a randomized, open-label phase 2/3 clinical trial of O+T versus investigator’s choice in advanced uLMS. Eligible patients have ECOG performance status ≤2, progression on ≥ 2 prior treatment lines and measurable disease. Patients are randomized 1:1 to receive T 75 mg/m2 orally daily + O 200 mg orally twice daily on days 1-7 in 21-day cycles (Arm 1) or investigator’s choice of trabectedin 1.5 mg/m2 over 24 hours every 21 days or pazopanib 400-600 mg orally daily (Arm 2). For phase 2, the primary endpoint is PFS. The design evaluates for an improvement in PFS from 4 mo to 8 mo, requires 70 patients, and yields 90% power and 1-sided alpha 0.10. If phase 2 is positive, phase 3 will enroll. For phase 3, the primary endpoint is overall survival (OS). The design evaluates for an improvement in OS from 13 mo to 23 mo, requires 165 patients (including 70 from phase 2) and yields 90% power with 1-sided alpha 0.025. Secondary endpoints include ORR, duration of response, safety and patient-reported outcomes. Archival tissue will be collected and evaluated with a RAD51 foci formation assay. Genomic sequencing results will be obtained where available. The study opened to accrual in 1/2023. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . Clinical trial information: NCT05633381 .
Engagement of patient participation in genomics research by the Osteosarcoma and Leiomyosarcoma Count Me In Projects of the Cancer Moonshot funded PE-CGS Network.
Authors: George Suzanne , Diehl Diane , Cibulskis Carrie , Merriam Priscilla , Smart Maeve , Doucette Jordan , Anastasio Elana , Zola Benjamin , Matthews Ashley , Ceca Evelina , Arssath Noorshifa , Lazo De La Vega Lorena , Benich Sidney , Sukharevsky Ellen , Winnicki Sarah , Fisher Lauren , Reardon Brendan Michael , Van Allen Eliezer Mendel , Mack Jennifer W. , Janeway Katherine A. 
Published: June 2023

TPS11588 Background: Osteosarcoma (OS) and Leiomyosarcoma (LMS) are sarcomas with complex genomes for which there has been limited progress in identifying new treatments and improving outcomes. Slow progress in OS and LMS is partially due to insufficient characterization of the genomic landscape. Generating large genomic datasets in OS and LMS is challenging because of the rarity of these sarcomas and recruitment barriers such as care fragmentation between institutions and specialties. The OS and LMS Project research studies aim to: 1) establish a network of engaged pediatric and adult participants with OS and LMS who will co-create a shared database of clinical, genomic, molecular, and patient reported data to enable research; 2) define the clinicogenomic landscape of OS and LMS; and 3) optimize the approach to direct patient engagement in cancer research. Methods: Count Me In, a research initiative with prior success in angiosarcoma, working with patients and advocates created websites (OSProject.org and LMSProject.org) where patients register and consent to participation. Projects were launched in September, 2022. After 5 months of accrual, 306 patients age 6-79 from 149 Institutions have consented. Blood and saliva are collected from consented participants, tumor samples are obtained from pathology departments and medical records are requested from treating hospitals. WES and WGS of tumor and normal, and RNASeq of tumor is performed. ctDNA is obtained and sequenced. Results are shared with patient, advocacy, physician and research communities in several ways. Individual participants receive a shared learning report describing the somatic variants identified in their tumor from paired tumor-normal WES and are offered genetic counseling and clinical germline testing. Registered participants receive updates via email and Project websites. There are regular pre-publication data releases to the genomic data commons and to cBioPortal. A physician engagement committee meets regularly to discuss clinical insights and conundrums from shared learning reports and germline testing. Patient accrual over the next 3 years is anticipated to result in sequencing of 750 tumor-normal pairs and 500 ctDNA samples.
A phase II study of palbociclib combined with retifanlimab in patients with advanced dedifferentiated liposarcoma.
Authors: D'Angelo Sandra P. , Rosenbaum Evan , Gularte Mérida Rodrigo , Dickson Mark Andrew , Keohan Mary Louise , Gounder Mrinal M. , Chi Ping , Movva Sujana , Kelly Ciara Marie , Avutu Viswatej , Chan Jason Earl , Cho Jae , Biniakewitz Matthew , Cho Grace , Erinjeri Joseph Patrick , Lefkowitz Robert A , Antonescu Cristina R. , Qin Li-Xuan , Singer Samuel , Tap William D. 
Published: June 2023

TPS11590 Background: Dedifferentiated liposarcoma (DDLPS) is characterized by near universal amplification of the cyclin-dependent kinase 4 ( CDK4) gene. Palbociclib (P) is a selective CDK4/6 inhibitor that has demonstrated promise in phase II studies of DDLPS. Anti-PD-1 therapy has also shown signals of efficacy, with an approximate overall response rate of 10% in DDLPS patients. CDK4/6 inhibitors upregulate antigen processing and presentation, suppress regulatory T cells, and increase inflammation within the tumor microenvironment. Combined with anti-PD-1 blockade, they can induce an inflamed T cell phenotype and tumor regression in pre-clinical models. We hypothesize that P combined with the anti-PD-1 inhibitor retifanlimab (R) will be safe and tolerable and have synergistic activity leading to activation of T cells and resultant clinical responses. Methods: NCT04438824 is a phase II study of P plus R with a safety lead-in phase. Patients with unresectable or metastatic DDLPS who have received any number of prior therapies are eligible to enroll. On the safety lead-in phase, 6 patients received P (125 mg once daily orally for 21 days followed by 7 days off) plus R (500 mg IV flat dose), repeated in 28-day cycles. P was initiated as monotherapy two weeks prior to initiation of R. The primary endpoint of the safety lead-in was to confirm the recommended phase two dose of the combination. Accrual to the safety lead-in has been completed and a pre-planned phase II expansion portion was opened to accrual. A study amendment was passed that revised the treatment schedule on the expansion cohort to start both P and R concomitantly on day 1 of each cycle. This revised schedule was based on recent data demonstrating the superior safety of a concurrent, rather than staggered, dosing schedule. The primary endpoint of the expansion phase is to estimate the best overall response rate (ORR) by RECIST 1.1. Secondary endpoints include describing the safety and estimating clinical benefit rate, duration of response, progression-free, and overall survival. A total of 30 patients treated with the revised dosing scheme will be enrolled onto the expansion phase. Twelve patients have been enrolled to date. An ORR of 5% will be considered not promising, while an ORR of 25% will be considered promising. The null hypothesis will be rejected if 4 or more patients have a confirmed objective response to treatment. This design has a type I error rate of 0.06 and a type II error rate of 0.04. Mandatory pre- and on-treatment biopsies will be performed for correlative analyses. Clinical trial information: NCT04438824 .
Comprehensive geriatric assessment based multidisciplinary team intervention for hospitalized frail patients in oncology: COMPASS-ONCO/KCSG AL21-13.
Authors: Lee Yun-Gyoo , Hwang In Gyu , Koh Su-Jin , Hong Soojung , Kim Jin Won , Kim Jee Hyun 
Published: June 2023

TPS12138 Background: Comprehensive geriatric assessment (CGA) is a multidimensional, interdisciplinary assessment for evaluating older patients’ medical, psychological, physical functions and social status. CGA-based multidimensional intervention is the gold standard in geriatric oncology to identify patients at high risk of adverse outcomes and optimize cancer and overall management. Numerous studies have demonstrated that CGA could modify oncologic treatment decision. However, little is known about the treatment outcomes of a multidisciplinary team intervention based on CGA. Methods: The COMPASS study is the first pragmatic multicentre trial within a cohort comprising three randomized controlled trials focusing on focusing on CGA and multidisciplinary intervention for hospitalised elderly patients in various healthcare settings of Korea. COMPASS-ONCO compares the effect of an oncologist-led multidisciplinary team intervention based on the CGA to that of conventional treatment for older cancer patients without the involvement of geriatricians. The patients will be randomised into the intervention or control groups in a 1:1 ratio. The inclusion criteria are as follows: (1) 65 years of age or older, (2) prefrail or frail status assessed by Korean version of the Fatigue, Resistance, Ambulation, Illnesses and Loss of Weight scale questionnaire, (3) having two or more of the following diseases; hypertension, diabetes, ischaemic heart disease, chronic lung disease, arthritis, stroke, depression, chronic kidney disease and dementia. (4) living at home for more than 3 months before hospitalization, (5) subject to palliative chemotherapy and (6) histologically confirmed gastric, colorectal, lung, pancreatic or biliary tract carcinoma. The intervention includes CGA and CGA-based multidisciplinary interventions by oncologists, nurses, nutritionists and pharmacists. The multidisciplinary intervention includes nutritional support, medication review and adjustment, rehabilitation, early discharge planning and prevention of geriatric syndromes (falls, delirium, pressure sore and urinary retention). The analysis will be based on an intention-to-treat principle. The primary outcome is overall treatment utility which is a clinical outcome incorporating objective and subjective measures of anticancer efficacy, tolerability and acceptability. Additionally, recognition of advance directives, changes in body composition and validity of anticancer drug toxicity prediction model will also be assessed. Approximately 1040 patients will be required for COMPASS study, and 260 will be enrolled in the COMPASS-ONCO substudy at five hospitals in Korea. Participants have been recruited from 2 November 2021, and recruitment will continue until December 2024. Clinical trial information: KCT0006270 .
Digital voice analysis as a measure of frailty and distress: A feasibility study (DIVAN).
Authors: Vetter Marcus , Hemm Simone , Schmid Cédric , Gaertner Jan 
Published: June 2023

TPS12139 Background: Assessing of frailty is essential not only in older patients with cancer, because frailty changes management of cancer therapy. Same is true for the routine assessment of distress to identify patient suffering and initiate adequate symptom control or psychosocial interventions. Here we present new potential method of frailty and distress assessment with digital voice analysis as a proof of concept trial. (NCT requested pending, DIVAN-1). Methods: Adult patients with the diagnosis of active incurable cancer can be enrolled into this study. Every participant will describe two to four images presented to him or her on a tablet computer in up to four sessions, and the patient`s voice will be recorded digitally. Baseline characteristics including cancer type, stage, therapy, G8 questionnaire and distress questionnaire (ESAS) will be collected at every session. Acoustic features like mean fundamental frequency (F0) and first few formants (F1, F2, etc.), jitter (variation in F0 from cycle to cycle), shimmer (variation in peak-to-peak amplitude), etc. will be explored digitally along with for example and voice strength (volume). Additionally, a vowel test will conducted and explored. Depending on the distribution of the data, the Pearson R correlation test or the Spearman’s R correlation test will be applied for each variable. The primary research question of this feasibility study is to identify quantitative parameters out of the audio signal to describe the changes in patient’s state in relation to frailty and distress. Trial enrolment has begun in December 2022 and 11 out of 100 patients have been included. Clinical trial information: NCT05783401 .
The CROWN study (CaRdiac outcomes with near complete estrogen deprivation): A multicenter, prospective cohort study of cardiovascular outcomes in premenopausal women with hormone receptor positive breast cancer treated with ovarian suppression and an aromatase inhibitor.
Authors: Douglas Emily H. , Park Carolyn J. , O'Connell Nathaniel S. , Ansley Katherine C. , Richardson Karl M. , Dent Susan Faye , Hackney Mary Helen Helen , D'Agostino Ralph , Hundley W. Gregory , Jordan Jennifer H. , Thomas Alexandra 
Published: June 2023

TPS12142 Background: Treatment for premenopausal women with high or intermediate risk hormone receptor (HR)+ breast cancer (BC) now includes the concurrent use of ovarian function suppression (OFS) and an aromatase inhibitor (AI) to induce near complete estrogen deprivation (NCED). The long-term cardiovascular (CV) sequela for women treated with NCED is unknown. Premature menopause in non-cancer populations is associated with CV disease. Taken together with the CV morbidity associated with other aspects of BC treatment and the future life-years of these women, the CV impact of NCED warrants further study. The CROWN study will use sophisticated imaging assessments of cardiac dysfunction to understand the evolution of CV injury, as well as biomarker and demographic correlates, with the goal of developing tools to assess and mitigate CV risk. Methods: This is a NIH funded prospective cohort study conducted at 3 regional NCI-supported Cancer Centers (Atrium Health Wake Forest Baptist, Virginia Commonwealth and Duke) that will include premenopausal women, age ≤ 55, with Stage I-III BC following completion of planned chemotherapy, surgery and radiation with an ECOG 0-1. HR+ BC patients will receive an AI and OFS. Women with HR- BC are included as comparators. CV imaging and biomarkers will be obtained at baseline, 1 year and 2 years (Table 1). These assessments will include serial cardiac magnetic resonance (CMR) and coronary computed tomography angiography (CCTA) imaging as well as laboratory measurements, including exploratory biomarkers. The primary objective is to determine the 24-month difference in stress myocardial blood flow as measured by adenosine CMR imaging in both groups. We will correlate CMR imaging with CCTA to provide complementary detail of coronary plaque changes. The study will also assess the relevance of pre-existing risk factors on study outcomes, including an emphasis on racial disparities, and dynamic change in modifiable and treatment related risk factors. We plan to enroll 90 women, 67 in the NCED group and 23 in the HR-group, allowing for a 10% drop out rate. There are two primary types of statistical analyses. The first includes testing hypotheses between group (NCED vs HR-) and within group (longitudinal changes within the NCED group). The second analyses, involve developing predictive equations utilizing a stepwise linear regression approach to determine if patient demographics, clinical parameters and serum biomarkers are associated with cardiovascular changes over time. Present accrual is 4. Clinical trial information: NCT05309655 . [Table: see text]
A randomized phase III clinical trial of acupuncture for chemotherapy-induced peripheral neuropathy in survivors of cancer.
Authors: Lopez-Nieves Ivana , Chiang Christopher , Han Katherine , Piulson Lauren , Seluzicki Christina , Weitzman Matthew , Zhang Yi Lily , Zhi Iris , Bao Ting 
Published: June 2023

TPS12144 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect in cancer survivors that can last long after completion of neurotoxic chemotherapy. Patients with CIPN often experience neuropathy symptoms such as pain, tingling, numbness, paresthesia, and dysesthesia, which can lead to significant functional decline and diminished quality of life. This outcome highlights the importance of developing effective CIPN treatments to improve quality of life for this population. Identifying nonpharmacological approaches to reduce CIPN symptoms and improve cancer survivors’ outcomes is urgently needed. Acupuncture is a widely used, minimally invasive Traditional Chinese Medicine technique that has shown promising evidence as an effective and safe treatment for CIPN. We hypothesize that acupuncture may reduce CIPN pain and improve overall CIPN symptoms in cancer survivors. Methods: We are conducting a two-arm, parallel randomized clinical trial comparing electroacupuncture (EA) versus sham acupuncture (SA) in cancer survivors. The EA arm includes ten sessions of EA over eight weeks using a standardized, semi-fixed protocol developed by our group. The SA arm includes a sham technique that uses a combination of non-acupuncture points and a non-insertion procedure in ten sessions over eight weeks. The primary outcome of this study is the Brief Pain Inventory-Short Form average pain item. The secondary outcomes are quantitative sensory testing measures and patient-reported outcomes that include the Neuropathic Pain Scale, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, CIPN-20, PROMIS Global Health Scale, and Patients' Global Impression of Change. The primary end point is week 12 and the secondary end point is week 24; treatment effects are assessed at baseline and at weeks 4, 8, 12, 18, and 24. The eligibility criteria includes: 1) Patients must be have no evidence of disease or have stable disease; 2) CIPN diagnosis with moderate-to-severe CIPN pain, defined by a score of 4 or greater on a scale 0-10 numerical scale rating; 3) completed neurotoxic chemotherapy at least three months prior; and 4) no changes in anti-neuropathy medications within three months of enrollment. As of February 2023, we have accrued 89 participants, with a total accrual target of 250 participants. Accrual completion is anticipated by December 2024. The demographic breakdown of our participants is as following: 71% white, 15% black or African American, 10% Asian, 3% more than one race, and 1% Native Hawaiian or Pacific Islander. 89% of the participants are non-Hispanic or Latino, 10% are Hispanic or Latino, and 1% are unknown. 71% of the participants are female and 29% are male. Clinical trial information: NCT04917796 .