bluuebunny/crossref_metadata_2025 huggingface dataset:
Update for NCI-COG Pediatric MATCH: Active trial cohorts for children, adolescents and young adults with refractory cancers.
Authors: Parsons Donald Williams , Janeway Katherine A. , Laetsch Theodore Willis , Irwin Meredith , Alva Elizabeth , Pratilas Christine A. , Franson Andrea Flynn , Patton David R. , Saguilig Lauren , Piao Jin , Alonzo Todd Allen , Berg Stacey L. , Fox Elizabeth , Hawkins Douglas S. , Mooney Margaret M. , Takebe Naoko , Tricoli James V. , Seibel Nita ,   NCI-COG Pediatric MATCH Team
Published: June 2023

TPS10071

Background: The National Cancer Institute–Children's Oncology Group Pediatric Molecular Analysis for Therapy choice (MATCH) trial seeks to facilitate evaluation of molecular-targeted therapies in biomarker-selected cohorts of childhood and young adult patients with cancer by screening tumors for actionable alterations. The Pediatric MATCH screening protocol and first seven treatment arms were activated in July 2017 for patients treated at COG sites across the United States; six additional treatment arms were activated between 2017 and 2020. In 2022 a major screening protocol amendment discontinued centralized tumor testing at MATCH laboratories and mandated use of molecular profiling reports from outside laboratories to determine treatment arm eligibility. Methods: The trial assigns patients aged 1 to 21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase 2 treatment arms of molecularly-targeted therapies based on the genetic alterations detected in their tumor. Starting in January 2022, a clinical tumor molecular profiling report from a CAP/CLIA-approved laboratory has been required for patients to enroll in the screening protocol. The treating site indicates which molecular alteration in the submitted report is believed to be actionable as well as the open Pediatric MATCH study arm for which the patient is proposed to be eligible. The submitted report is then reviewed by the study Molecular Review Committee to determine if an actionable alteration is present (based upon study-defined levels of preclinical and clinical evidence): if so, the patient is assigned to the relevant MATCH treatment arm. Other treatment arm eligibility requirements are typical of phase 2 pediatric trials including adequate patient performance status and standard washout periods for prior therapy. Each treatment arm follows a one (arms A, D, F, M, N) or two (arm K) stage design with a 20 patient primary cohort and option for histology-specific expansion cohort(s) if at least 3 objective responses are seen in a tumor histology. The primary endpoint is objective response rate; secondary endpoints include safety/tolerability and progression-free survival. Therapy is discontinued if there is evidence of progressive disease or drug related dose-limiting toxicity that requires removal from therapy; therapy may otherwise continue for up to 2 years. As of January 2023, 6 of the 13 Pediatric MATCH treatment arms remain open to enrollment (Table). Clinical trial information: NCT03155620 . [Table: see text]
Phase IIa study of αDC1 vaccines targeting HER2/HER3 combined with pembrolizumab in patients with asymptomatic brain metastasis from triple negative breast cancer or HER2+ breast cancer.
Authors: Gandhi Shipra , Forsyth Peter A. J. , Opyrchal Mateusz , Ahmed Kamran A. , Attwood Kristopher , Levine Ellis Glenn , O'Connor Tracey L. , Early Amy P. , Fenstermaker Robert Alan , Prasad Dheerendra , Takabe Kazuaki , Czerniecki Brian J. , Kalinski Pawel
Published: June 2023

TPS1112

Background: Brain metastases develop in up to 50% patients (pts) with metastatic triple negative breast cancer (TNBC) and HER2+ BC, constituting an increasing source of morbidity and mortality. HER3, overexpressed in triple negative and HER2+ brain metastatic breast cancer (BMBC), is a resistance factor to HER2-targeted therapies and a driver of CNS metastasis. Disease progression is associated with loss of anti-HER2 and anti-HER3 immunity. Previously, we have demonstrated that glioma-specific peptide-loaded αDC1 which produce CXCL9, CXCL10, CXCL11, CCL5, the chemokines which attract CXCR3- and CCR5- expressing cytotoxic T-lymphocytes (CTLs) and T-helper 1 (Th1) cells, induce clinical responses and long-term disease stabilization in pts with aggressive recurrent primary brain tumors (Okada et al. JCO 2011. PMID: 21149657). We hypothesized that anti-HER2/3-loaded αDC1 in combination with PD1 blockade will result in strong Th1/CTL response against HER2/3 epitopes (Basu A et al. Cancer Immunol Res. 2022 PMID: 34785506), being effective against brain lesions and systemic disease. Methods: This is a phase II single-arm, non-randomized multicenter study (NCT04348747). Eligibility includes pts with triple negative and HER2+ BMBC ≥18 years, ECOG PS ≤1, normal marrow and organ function with asymptomatic untreated brain metastases ≥ 5 mm who will receive αDC1 q3 weeks x 3 along with pembrolizumab every 3 weeks. Thereafter, αDC1 booster doses (if available) would be administered every 3 months until disease progression, intolerable side effects or withdrawal from study, up to 24 months. Baseline and 9-week post-αDC1 peripheral biopsies (non-CNS) are required for six pts. 1 of the planned 21 pts have been enrolled and is undergoing treatment. Primary endpoint is CNS response rate (RR) by RANO-BM criteria. If no CNS response is observed after 12 pts, study will be terminated. If ≥ 1 response observed, then 9 more pts will be enrolled, for a total of 21 pts. If ≥ 3 CR are observed, the proposed therapy will be considered as promising for further evaluation. Secondary endpoints include non-CNS RR per RECIST v1.1, median CNS, non-CNS and overall progression-free survival, overall survival and safety. Exploratory endpoints include changes in intratumoral biomarkers (CTLs, PDL1, chemokines) in pre- and post-treatment peripheral tumor biopsies and immune changes in the blood. Clinical trial information: NCT04348747 .
VERITAC-2: A global, randomized phase 3 study of ARV-471, a proteolysis targeting chimera (PROTAC) estrogen receptor (ER) degrader, vs fulvestrant in ER+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer.
Authors: Campone Mario , Ma Cynthia X. , De Laurentiis Michelino , Iwata Hiroji , Hurvitz Sara A. , Wander Seth Andrew , Danso Michael A. , Lu Dongrui Ray , Perkins Smith Julia , Liu Yuan , Tran Lana , Anderson Sibyl , Hamilton Erika P.
Published: June 2023

TPS1122

Background: ARV-471 is an oral PROTAC ER degrader that binds to and degrades wild-type ER and clinically relevant mutants. ARV-471 directly recruits the ubiquitin-proteasome system to degrade ER, whereas selective ER degraders (SERDs) indirectly cause ER degradation. In a first-in-human phase 1/2 study, ARV-471 monotherapy was well tolerated and showed clinical activity in heavily pretreated patients with ER+/HER2- advanced breast cancer. The phase 3 monotherapy dose (200 mg once daily [QD]) was chosen due to comparable efficacy and favorable tolerability relative to 500 mg QD and robust ER degradation in paired tumor biopsies. The randomized phase 3 VERITAC-2 study (NCT05654623) will compare efficacy and safety of ARV-471 vs the SERD fulvestrant in patients with ER+/HER2- advanced breast cancer after prior combination cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy and endocrine therapy (ET). Methods: Eligible patients (aged ≥18 years) have a confirmed diagnosis of ER+/HER2- locoregional recurrent or metastatic breast cancer not amenable to surgical resection or radiation; 1 prior line of combination CDK4/6 inhibitor therapy and ET; ≤1 additional line of ET; most recent ET given for ≥6 months before disease progression; and radiological disease progression during or after the last line of therapy. Prior chemotherapy in the locally advanced or metastatic setting and prior fulvestrant are not permitted. Patients (N~560) are randomized 1:1 to receive 200 mg ARV-471 orally QD continuously or fulvestrant intramuscularly on days 1 and 15 in the first 28-day cycle and on day 1 in subsequent cycles; patients are stratified by ESR1 mutation status and presence of visceral disease. The primary endpoint, progression-free survival, will be assessed by blinded independent central review in the intention-to-treat population and the ESR1 mutation sub-population. Secondary outcome measures include overall survival, antitumor activity (objective response rate, duration of response, and clinical benefit rate), safety, and quality of life assessments. Clinical trial information: NCT05654623 .
CAPTOR-BC: Comprehensive analysis of spatial, temporal and molecular biomarkers predicting response and resistance to first-line treatment with ribociclib + ET in HR+, HER2- advanced breast cancer.
Authors: Fasching Peter A. , Brucker Sara , Huebner Hanna , Thewes Verena , Volmer Lea Louise , Hartkopf Andreas Daniel , Kolberg Hans-Christian , Lex Benno , Aktas Bahriye , Ditsch Nina , Haeberle Lothar , Seitz Katharina , Anetsberger Daniel , Nabieva Naiba , Roos Christian , Belleville Erik , Schneeweiss Andreas , Mueller Volkmar , Janni Wolfgang , Fehm Tanja N.
Published: June 2023

TPS1124

Background: The combination of an oral CDK4/6 inhibitor with endocrine therapy (ET) has become the standard first-line therapy for women with advanced HR+ HER2- breast cancer. In this context, the broadest clinical trial data are available for ribociclib, a highly selective CDK4/6 inhibitor, with three phase III trials (MONALEESA-2, -3 and -7) consistently showing a significant overall survival benefit compared to ET monotherapy regardless of treatment line, menopausal status or combination partner. However, de novo or acquired resistance to CDK4/6 inhibitors does occur and biomarkers predicting treatment response or providing information on resistance mechanisms are only beginning to be understood. Comprehensive identification and validation of biomarkers before and during ribociclib therapy is needed to better understand mechanisms leading to disease progression, which will be the first step towards developing novel therapies and optimizing treatment sequences. Methods: CAPTOR-BC (NCT054552213) is a single-arm, open-label phase IV study evaluating the combination of ribociclib and ET according to SmPC in the first-line treatment of HR+ HER2- advanced breast cancer to identify and validate molecular and non-molecular biomarkers predictive of drug response and resistance. First patient first visit occurred in October 2022 and at least 1000 patients across more than 75 sites in Germany will be enrolled until October 2025. Progression-free survival (PFS) and overall survival (OS) at 12 months are the co-primary endpoints, quality of life (QoL) and toxicity are secondary endpoints. Exploratively, a comprehensive multi-omics biomarker discovery and validation program is integrated into the study: Besides tumor tissue, liquid biopsies profiling circulating tumor (ct)DNA, ctRNA, whole blood RNA, proteins from serum and plasma, and circulating immune cells will be evaluated before, during and after treatment or upon progression to determine correlations with PFS, OS, QoL and adverse events. Clinical trial information: NCT05452213 .
A phase 1b/2 dose escalation and expansion study of OP-1250 in combination with ribociclib or alpelisib in patients with advanced and/or metastatic estrogen receptor–positive (ER+)/HER2-negative (HER2-) breast cancer.
Authors: Borges Virginia F. , Chan Arlene , Lin Nancy U. , Tonda Margaret Eleanor , Shilkrut Mark , Alemany Carlos A.
Published: June 2023

TPS1127

Background: Therapies targeting the estrogen receptor (ER) are standard of care in the management of ER+/HER2- metastatic breast cancer (MBC) and when administered concurrently with cyclin-dependent kinase (CDK) inhibitors are the most effective first-line therapy. CDK 4/6 inhibitors plus endocrine therapy improve progression-free survival and, for some agents, overall survival for patients with MBC. However, most patients will acquire resistance, highlighting an unmet need for more effective endocrine options in ER+ disease. OP-1250 is a small molecule oral complete estrogen receptor antagonist (CERAN) and selective estrogen receptor degrader (SERD) that binds the ligand binding domain of ER and completely blocks ER-driven transcriptional activity. OP-1250 potently inactivates both wild-type and mutant forms of ER, the latter of which confers ligand independent activity as a mechanism of resistance to standard of care endocrine therapies. In preclinical studies, OP-1250 in combination with CDK4/6 inhibitors demonstrated synergistic activity in models of both wild-type ER and those with ESR1 (the gene that encodes ER) activating mutations, and in brain metastasis. OP-1250 is orally bioavailable with a favorable pharmacokinetic (PK) profile supportive of once-daily dosing, and a low probability of drug:drug interactions, making it an attractive agent for patients with ER+/HER2- MBC. Methods: The study (NCT05508906) is an open-label, multicenter, 2-part study of OP-1250 in combination with either the CDK4/6 inhibitor ribociclib or the PI3K inhibitor alpelisib for patients with MBC. Eligibility includes adults with evaluable (measurable or non-measurable) ER+/HER2- recurrent, locally advanced or MBC confirmed by histology/cytology, ≤2 prior hormonal regimens (prior CDK4/6 inhibitors allowed) and ≤ 1 prior line of chemotherapy. Patients in the alpelisib arm must have a PIK3CA mutation. A total of 30 patients will be enrolled in each arm. The dose escalation cohorts will evaluate the safety and PK of varied OP-1250 doses (30mg, 60mg, or 120mg) administered orally (PO) every day (QD) in combination with approved dosages of either ribociclib 600 mg PO QD or alpelisib 300 mg PO QD to identify the recommended phase 2 doses (RP2D). The dose expansion cohorts will assess additional safety and PK parameters and further explore the anti-tumor activity of OP-1250 in combination with ribociclib or alpelisib. Tolerability, safety and PK of OP-1250 in combination with ribociclib or alpelisib constitute the primary endpoints. Overall response rate, clinical benefit rate and duration of response are key secondary endpoints. Enrollment at approximately 20 sites in the United States and Australia is ongoing. Clinical trial information: NCT05508906 .
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 .
Phase 2 study to assess the efficacy, safety, and tolerability of the GDF-15 inhibitor ponsegromab in patients with cancer cachexia.
Authors: Crawford Jeffrey , Lubaczewski Shannon L , Tarachandani Anil , Harrington Magdalena A , Weng Yan , Qiu Ruolun , Collins Susie M , Rossulek Michelle I , Revkin James H
Published: June 2023

TPS12147

Background: Cancer cachexia is a multifactorial metabolic syndrome of wasting characterized by anorexia, unintended weight loss, and decreased skeletal muscle mass, leading to progressive functional impairment, fatigue, diminished quality of life, poor response to anticancer therapy, and reduced survival. One of the biomarkers associated with cancer cachexia is cytokine growth differentiation factor 15 (GDF-15), which is secreted by tumor cells. Preliminary phase 1 data suggest that suppression of GDF-15 may lead to improvement in cachexia-related symptom burden. Ponsegromab is a potent and selective humanized monoclonal antibody that inhibits GDF-15-mediated signaling. The primary objective of this study (NCT05546476) is to assess the effect of ponsegromab on body weight in patients with cancer, cachexia, and elevated circulating GDF-15 concentrations. Secondary objectives include assessing physical activity, gait, anorexia/appetite, nausea and vomiting, fatigue, and safety. Exploratory objectives include evaluating pharmacokinetics, pharmacodynamics, and immunogenicity. Methods: This phase 2 study will enroll approximately 168 adults with non–small cell lung, pancreatic, or colorectal cancers who have cachexia and elevated GDF-15 concentrations. The study will be conducted in 2 parts. The initial 12-week treatment period will be a randomized, double-blind, placebo-controlled study wherein participants who meet eligibility criteria will be randomized 1:1:1:1 to one of 3 dose groups of ponsegromab (administered subcutaneously [SC] every 4 weeks [Q4W]) or placebo. The double-blind period will be followed by optional open-label treatment (OLT) with ponsegromab Q4W SC for up to 1 year. Upon completion of the optional OLT period, there will be a follow-up visit at Week 72. Participants who do not proceed with the optional OLT period will complete the Week 12 visit and a follow-up visit at Week 16. The primary endpoint is the mean change from baseline in body weight at Week 12. A mixed model for repeated measures followed by a Bayesian Emax model will be used for the primary analysis. Secondary endpoints include physical activity and gait measured by remote digital sensors; patient-reported appetite-related symptoms assessed by Functional Assessment of Anorexia-Cachexia Therapy scores; anorexia/appetite, nausea, vomiting, and fatigue evaluated according to questions from the Cancer-related Cachexia Symptom Diary; and incidence of adverse events, safety laboratory tests, vital signs, and electrocardiogram abnormalities. © 2023 American Association for Cancer Research®. Reused with permission. Clinical trial information: NCT05546476 .
Study for the prevention of oral mucositis.
Authors: Oganesyan Artem , Harutyunyan Lusine , Vanoyan Araksya , Martirosyan Nare , Badikyan Maria , Ghahramanyan Nerses , Oseyan Hasmik , Evoyan Levon , Farmazyan Armine , Chakhoyan Amalya , Grigoryan Hayk , Ter-Grigoryan Anahit , Sevoyan Anna , Gharibyan Avetis , Aynajyan Anahit , Hakobyan Karapet , Hakobyan Yervand
Published: June 2023

TPS12149

Background: Oral mucositis (OM) is a serious complication of cancer treatments characterized by erythema and ulcerations of the mouth. Consequences of OM include pain, diminished functionality, and infections leading to decreased quality of life and discontinuity in therapy. About 20-40% of patients receiving chemotherapy develop OM within 7 days of treatment initiation. Current clinical guidelines recommend prophylactic oral care, cryotherapy, KGF-1, palifermin, and photobiomodulation to prevent OM in specific patient groups. Benzydamine is approved for the prevention of OM in head and neck cancer patients receiving radiotherapy or radio-chemotherapy but has not been well studied for chemotherapy alone. The effectiveness of oral topical treatments is limited by dilution in the saliva and swallowing shortening the duration of their action. Bocaliner is a novel medical device that is hypothesized to enhance the effects of treatments by prolonging the oral retention of topical therapies within the oral cavity. Methods: The Study for the Prevention of Oral Mucositis (SPOM) is a randomized controlled Phase I/II trial that aims to evaluate the efficacy of two different tools (benzydamine mouthwash and Bocaliner) in reducing the incidence and severity of OM in patients undergoing systemic chemotherapy (NCT05338398). A total of 100 adult patients with hematologic malignancies undergoing chemotherapy in a centralized hematology center in Armenia will be randomized into two different treatment groups: saline mouthwash and benzydamine mouthwash (0.15%, 120mL) 3-5 times a day for a total of two weeks. Half of the patients within each group will also randomly receive Bocaliner, which will be placed inside of their mouth immediately after the application of the mouthwash for 20 minutes. Block randomization will be applied with 4 patients per block with 1:1 randomization based on gender, Bocaliner use, and mouthwash type. The primary endpoint is the difference in OM incidence measured by the WHO Oral Toxicity Scale. The secondary endpoints are differences in OM symptoms evaluated using a modified version of the PROMS questionnaire. Safety and tolerability of the medical device will be determined for the Phase I component of the study based on responses to standardized tryout (Day 0) and follow-up questionnaires (Day 14). Other outcomes include the duration and severity of OM. Statistical analysis will explore further clinically meaningful associations between patient data, received therapies, and outcomes. Forty-two patients have already completed the study, while the enrollment of other participants continues and is planned to be completed by the end of 2023. Clinical trial information: NCT05338398 .
Exploratory study investigating the efficacy and safety of olanzapine prophylaxis for opioid-induced nausea and vomiting (JORTC-PAL20).
Authors: Satomi Eriko , Ishikawa Ayaka , Arakawa Sayaka , Ishiki Hiroto , Amano Koji , Kobayashi Tomomi , Sakiyama Naomi , Otsuka Ryo , Maeda Makoto , Hashimoto Hironobu , Oyamada Shunsuke , Ariyoshi Keisuke , Kihara Kota , Mizushima Akio
Published: June 2023

TPS12151

Background: In opioid therapy for cancer pain, it is essential to manage opioid-related adverse effects. Opioid-induced nausea and vomiting (OINV) is common, occurring in 20–40% of patients during initial opioid treatment or after opioid doses are increased. Tolerance to OINV develops within a few days to a week. In patients with cancer, OINV results in decreased quality of life as well as failure to relieve pain due to poor opioid adherence, thus increasing the psychological barriers to opioid use. Therefore, antiemetics are used for OINV prophylaxis, but their efficacy and safety in this context have not yet been fully elucidated. Olanzapine is a promising antiemetic for prophylaxis against nausea and vomiting induced by highly emetogenic chemotherapy, and it is less likely to cause extrapyramidal symptoms than haloperidol and prochlorperazine. We are conducting this exploratory study to evaluate the efficacy and safety of olanzapine prophylaxis against OINV. Methods: This single-arm, single-center exploratory study will evaluate the prophylactic antiemetic efficacy and safety of olanzapine (5 mg PO once a day for 5 days) in patients with cancer pain reserving initial regular opioid therapy. Thirty-five patients will be enrolled. This study was designed to provide preliminary efficacy data, with a primary objective of assessing the proportion of patients who achieved complete control (CC) of OINV during 120 hours of opioid treatment. CC was defined as the absence of emetic episodes, the lack of a need for rescue medication to treat nausea, and minimal or no nausea (3 or less on an 11-point categorical scale). Secondary endpoints include the following: the complete response (CR) rate, defined as the percentage of patients with no emetic episodes and no rescue medication use; the total control (TC) rate, defined as the percentage of patients with no emetic episodes, no rescue medication use, and no nausea during the 120 hours of opioid treatment; the time from opioid initiation to the first emetic episode; the time from opioid initiation to the first administration of a rescue antiemetic; the time to treatment failure, defined as the time from opioid initiation to the first emetic episode or to the administration of a rescue antiemetic; the number of emetic episodes; the levels of nausea, anorexia, sleepiness, pain, and fatigue, all determined using a numerical rating scale (0–10); the impact of antiemetic therapy on daily life severity and patient satisfaction, determined using a 7-grade categorical scale; and adverse events graded by PRO-CTCAE ver.1.0 and CTCAE ver. 5.0. The study is currently open, and 25 patients have been enrolled at time of abstract submission. Clinical trial information: jRCTs031220008 .