bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line chemotherapy in patients (pts) with advanced HER2-negative gastric or gastroesophageal junction cancers: The ARMANI phase III trial.
Authors: Morano Federica , Niger Monica , Corallo Salvatore , Lonardi Sara , Tamberi Stefano , Di Donato Samantha , Giommoni Elisa , Giuliani Francesco , Frassineti Giovanni Luca , Tomasello Gianluca , De Vita Ferdinando , Cardellino Giovanni Gerardo , Pinotti Graziella , Brizzi Maria Pia , Rimassa Lorenza , Scartozzi Mario , Berardi Rossana , De Braud Filippo G. , Pietrantonio Filippo , Di Bartolomeo Maria 
Published: May 2019

TPS4151 Background: Platinum/fluoropyrimidine regimens are the backbone of first-line therapy for advanced gastric cancer (AGC). The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only 40% of AGC pts are eligible for second-line treatment. This study aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after a first-line with a platinum/fluoropyrimidine regimen. The hypothesis is that the early administration of an active, non-cross resistant regimen may delay disease progression and, consequently, improve pts’ quality of life. This strategy may also rescue all those subjects that become ineligible for a second-line therapy due to the rapid clinical deterioration. Methods: This is a randomized, open-label, multicenter, phase III trial. Eligibility criteria are: unresectable/metastatic HER-2 negative AGC or gastroesophageal junction (GEJ) cancer; ECOG PS 0-1; measurable and/or evaluable disease by RECIST v1.1; no progression after 3 months of therapy with either FOLFOX4, mFOLFOX6 or XELOX . The primary endpoint is to compare PFS of pts in ARM A (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine) versus ARM B (switch maintenance to ramucirumab and placlitaxel). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of pts receiving a second-line therapy per treatment arm, safety and quality of life. Exploratory analyses to identify primary resistance and prognosis biomarkers are planned, including Next-Generation Sequencing (NGS) on archival tumor tissues. The ARMANI study is sponsored by the Fondazione IRCCS Istituto Nazionale dei Tumori and it is ongoing at 29 Italian centers with a planned population of 280 pts. Clinical trial information: NCT02934464.
NUC-1031 in combination with cisplatin for first-line treatment of advanced biliary tract cancer.
Authors: Knox Jennifer J. , McNamara Mairead Geraldine , Palmer Daniel H. , Evans T.R. Jeffry , Goldstein David , Bridgewater John A. , Valle Juan W. 
Published: May 2019

TPS4156 Background: Cisplatin and gemcitabine (CisGem) is the global standard of care for 1st-line treatment of patients (pts) with advanced biliary tract cancer (BTC). No agents have regulatory approval for this disease. CisGem achieves an objective response rate (ORR) of 26% and median overall survival (OS) of 11.7 months (ABC-02). Key cancer resistance mechanisms limit gemcitabine efficacy. NUC-1031, a phosphoramidate transformation of gemcitabine, is designed to overcome resistance mechanisms associated with poor gemcitabine response. Promising signs of efficacy have been observed with single agent in a phase I study in solid tumors (Blagden et al 2018) and in the phase Ib ABC-08 study of NUC-1031 + cisplatin 25 mg /m2 d1, d8 q 21 days for the 1st-line treatment of advanced BTC. 14 pts have been enrolled across 2 cohorts (NUC-1031: 625 mg/m2 and 725 mg/m2). In 11 pts evaluable for response ORR was 64% (1 CR, 6 PRs) and DCR was 73%. PFS/OS data is maturing. The combination was very well-tolerated with no unexpected adverse events or dose-limiting toxicities. The RP2D in combination with cisplatin is 725 mg/ m2. Safety, coupled with encouraging efficacy signal has led to initiation of a global Phase III development program. Methods: A Phase III, open-label, randomized head-to-head study of NUC-1031 + cisplatin versus CisGem for the 1st-line treatment of advanced BTC will include pts ≥18 years with histologically- or cytologically-proven BTC (including cholangiocarcinoma, gallbladder, or ampullary cancer), that is not resectable and who have had no prior systemic chemotherapy for locally advanced/metastatic disease. A total of 828 pts will be randomized (1:1) to either 725 mg/m2 NUC-1031 + 25 mg/m2 cisplatin or 1000 mg/m2 gemcitabine + 25 mg/m2 cisplatin, administered on Days 1 and 8 of a 21-day cycle, respectively. Primary objectives are OS and ORR. Secondary objectives include further measurements of efficacy, safety, pharmacokinetics, and patient-reported quality of life. The study will be conducted at approximately 120 sites across North America, Europe and Asia Pacific countries. Clinical trial information: NCT02351765.
Phase 2 trial of Lu-177-DOTATATE in inoperable pheochromocytoma/paraganglioma.
Authors: Lin Frank , Del Rivero Jaydira , Carrasquillo Jorge A. , Jha Abhishek , Gonzales Melissa K , Lindenberg Liza , Turkbey Baris , Lin Emily , Mena Esther , Millo Corina , Chen Clara , Herscovitch Peter , Choyke Peter L. , Pacak Karel 
Published: May 2019

TPS4159 Background: Pheochromocytoma/paraganglioma (PHEO/PGL) is a rare malignancy that arises from chromaffin cells of typically the adrenal medulla but can also be of extra-adrenal origin. These tumors produce excessive catecholamines such as epinephrine and norepinephrine which causes labile hypertension, tachycardia, and flushing. Lu-177-DOTATATE (Lu-177-dodecanetetraacetic acid‐tyrosine-3-octreotate) is a radiolabeled somatostatin analog that is FDA approved for somatostatin receptor-positive neuroendocrine tumors. It is being being investigated in PHEO/PGL, which overexpress somatostatin receptors. Amino acid solutions containing lysine/arginine (L/A) are routinely co-administered with Lu-177-DOTATATE for renal radioprotection, although solutions containing other amino acids are also used. Methods: This is a prospective, single center, open label Phase 2 study evaluating the efficacy of Lu-177-DOTATATE in PHEO/PGL. Ninety patients will be enrolled, divided into two cohorts of 45 patients each ( SDHx mutation vs. apparent sporadic). Lu-177-DOTATATE is given at a fixed dose of 200 mCi with a co-administration of L/A amino acid solution q8 weeks for 4 cycles. The primary endpoint is the progression-free-survival (PFS) rate at 6 months. Secondary endpoints include response rate, overall survival, time to progression, quality of life measures, and examination of potential biomarkers such as biochemical profiles, Ga-68-DOTATATE PET, and F-18-FDG PET scans. Eligibility criteria include inoperable disease (including non-metastatic), histological confirmation of PHEO/PGL, evidence of disease progression by RECIST 1.1, ECOG performance status of 1 or better, and a positive Ga-68-DOTATATE PET scan. Exclusion criteria include prior treatment with systemic radionuclide therapy such as I-131-MIBG, brain parenchymal metastases, and standard organ dysfunction limitations. Interim analysis using a Simon two-stage optimal design will be performed separately for each cohort after enrollment of 18 patients. First patient accrual to this ongoing study was in the Fall of 2017, and as of February 2019, fourteen patients have been accrued. Preliminary results will be reported at the completion of stage 1 for each cohort. Clinical trial information: NCT03206060.
A randomized phase II trial of niraparib plus either nivolumab or ipilimumab in patients with advanced pancreatic cancer whose cancer has not progressed on platinum-based therapy.
Authors: Reiss Kim Anna , Mick Rosemarie , O'Hara Mark H. , Teitelbaum Ursina R. , Karasic Thomas Benjamin , Schneider Charles John , O'Dwyer Peter J. , Karlson Danielle , Cowden Stacy , Fuhrer Mary Jane , Carpenter Erica L. , Pantel Austin A , Makvandi Mehran , Mankoff David A. , Nathanson Katharine , Maxwell Kara Noelle , Beatty Gregory Lawrence , Domchek Susan M. 
Published: May 2019

TPS4161 Background: The treatment paradigm for advanced pancreatic ductal adenocarcinoma (PDAC) typically involves ongoing chemotherapy until either disease progression or clinical deterioration. A subset of patients with advanced PDAC have exceptional responses to platinum-based chemotherapy. We hypothesized that durable platinum sensitivity in patients with advanced PDAC might be indicative of a DNA repair deficiency, and that these patients may respond to a combination of niraparib, a PARP inhibitor, plus immune checkpoint blockade. Methods: We have enrolled 25 of 84 planned patients on study NCT 03404960. Eligibility criteria include inoperable PDAC and stability on platinum-based chemotherapy for ≥16 weeks without evidence of progressive disease. Patients who have progressed on platinum-based treatment or who have received prior therapy with PARP inhibitors are excluded. Patients are randomized to receive oral niraparib 200mg PO daily plus nivolumab 240mg IV every two weeks in continuous 28 day cycles or oral niraparib 200mg PO daily plus ipilimumab 3mg/kg IV every three weeks for four doses in continuous 21 day cycles. The primary endpoint is progression-free survival at 6 months. Secondary endpoints include response rate, duration of response and overall survival. Paired biopsies are obtained, as well as serial blood collections for circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and peripheral blood mononuclear cells (PBMCs). Correlative assays will include germline whole exome sequencing and analyses of serially collected PBMCs, CTCs and ctDNA to identify genomic and immunologic innate and adaptive resistance mechanisms. Clinical trial information: NCT 03404960.
Improving cascade genetic testing for families with inherited pancreatic cancer (PDAC) risk: The genetic education, risk assessment and testing (GENERATE) study.
Authors: Yurgelun Matthew B. , Furniss C. Sloane , Kenner Barbara , Klein Alison , Lafferty Catherine C. , Lowy Andrew M. , McAllister Florencia , Mork Maureen E , Nelson Scott H. , Robertson Alison , Stopfer Jill E. , Underhill Meghan , Ocean Allyson J. , Madlensky Lisa , Petersen Gloria M. , Garber Judy Ellen , Lippman Scott Michael , Goggins Michael , Maitra Anirban , Syngal Sapna 
Published: May 2019

TPS4162 Background: 4-10% of PDAC patients harbor pathogenic germline variants in cancer susceptibility genes, including APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, and TP53. For families with such pathogenic variants, the greatest potential impact of germline testing is to identify relatives with the same pathogenic variant (cascade testing), thereby providing the opportunity for early detection and cancer interception of PDAC and other associated malignancies. Numerous factors limit cascade testing in real-world practice, including family dynamics, widespread geographic distribution of relatives, access to genetic services, and misconceptions about the importance of germline testing, such that the preventive benefits of cascade testing are often not fully realized. The primary aim of this study is to analyze two alternative strategies for cascade testing in families with inherited PDAC susceptibility. Methods: 1000 individuals (from approximately 200 families) with a confirmed pathogenic germline variant in any of the above genes in a 1st/2nd degree relative and a 1st/2nd degree relative with PDAC will be remotely enrolled through the study website (www.generatestudy.org) and randomized between two different methods of cascade testing (individuals with prior genetic testing will be ineligible): Arm 1 will undergo pre-test genetic education with a pre-recorded video and live interactive session with a genetic counselor via a web-based telemedicine platform (Doxy.me), followed by germline testing through Color Genomics; Arm 2 will undergo germline testing through Color Genomics without dedicated pre-test genetic education. Color Genomics will disclose results to study personnel and directly to participants in both arms. Participants in both arms will have the option of pursuing additional telephone-based genetic counseling through Color Genomics. The primary outcome will be uptake of cascade testing. Secondary outcomes will include participant self-reported genetic knowledge, cancer worry, distress, decisional preparedness, familial communication, and screening uptake, which will be measured via longitudinal surveys. Enrollment will begin February, 2019. Clinical trial information: NCT03762590.
PRIMUS-002: A multicentre, open-label, phase II study examining FOLFOX and nab-paclitaxel (FA) and nab-paclitaxel and gemcitabine (AG) as neoadjuvant therapy for (borderline) resectable pancreatic cancer (PC), focusing on biomarker and liquid biopsy development.
Authors: Grose Derek B. , McKay Colin J , Cooke Susie , Graham Janet Shirley , Duthie Fraser , Jamieson Nigel , Ravikumar Reena , Duffton Aileen , McIntosh David , Goody Rebecca , Radhakrishna Ganesh , Hawkins Maria A , Colville Dave , Willshire Christine , Stobo Jon , Paul James , Bradley Sarah , Dixon-Hughes Judith , Biankin Andrew Victor , Chang David Kuang-Fu ,   Andrew Biankin
Published: May 2019

TPS4166 Background: There is increasing evidence suggesting benefit from a neoadjuvant approach to PC. However, the optimal regimen is unclear and will likely require a precision medicine approach, where patient and tumor attributes define therapy. Platinum-containing regimens have shown survival benefit for PC, with occasional exceptional responders, but biomarkers (BM) of response are not well defined and treatment decisions are often based on patient performance status (PS) and co-morbidity. Tumors with defects in BRCA1/2and other Fanconi Anemia genes show defective DNA damage response (DDR), conferring potential selective sensitivity to DNA-damaging agents (e.g. platinum) and newer targeted agents. We have shown that DDR deficiency (DDRd) is present in up to 20% of PC. This study aims to exploit DDRd as a therapeutic vulnerability, with integrated analysis to define candidate BM for FA and AG response. Methods: PRIMUS-002 will enroll patients registered on the Precision-Panc Master Protocol who are molecularly profiled using the Precision-Panc Clinical Cancer Genome including a novel DDRd assay, and the transcriptome with longitudinal sampling (pre-, during, and post-treatment). Patients receive either FA ( nab-paclitaxel 150mg/m2IV,oxaliplatin 85mg/m2, folinic acid 350mg flat dose, fluorouracil infusion 2400mg/m2continuous IV infusion), orAG ( nab-paclitaxel 125mg/m2, gemcitabine 1000 mg/m2) for 3 months,based on patient age and PS.Following initial safety analysis, chemoradiation may be introduced. The primary endpoint is disease progression (DP) during neoadjuvant therapy. The study is designed to detect a 20% difference in DP between the BM+ve (10%) and BM –ve (30%) in patients treated with FA (90% power, 5% 1-sided level of statistical significance)., Exploratory translational endpoints include surrogate therapeutic response assessment using CA19.9, PET-CT SUV, DWI-MRI and ctDNA. Current Enrolment: 2 patients enrolled to date: 1 to receive FA and 1 to AG treatment. Clinical trial information: ISRCTN34129115.
A randomized phase II study of atezolizumab plus recombinant human IL-7 (CYT107) or atezolizumab alone in patients with locally advanced or metastatic urothelial carcinoma (mUC): A Cancer Immunotherapy Trials Network Trial (CITN-14).
Authors: Yu Evan Y. , Fling Steven , Salim Bob , Sweis Randy F. , Chatta Gurkamal S. , Jain Rohit K. , Delacroix Scott Edward , Moon Helen , Lacroix Andreanne , Kaiser Judith C , Sharon Elad , Cheever Martin A. , Pachynski Russell 
Published: May 2019

TPS4586 Background: Atezolizumab is a regulatory-approved PD-L1 antagonistic antibody for the post-platinum mUC setting. Responses to atezolizumab are highly efficacious in a subset of patients, but suboptimal or absent in most patients. IL-7 (CYT107) is a homeostatic growth factor that promotes proliferation, differentiation, and survival of T lymphocytes. We recently demonstrated CYT107 significantly increases peripheral absolute lymphocyte and T cell numbers in metastatic castration-resistant prostate cancer patients when administered after sipuleucel-T. We hypothesize expansion of T cells by CYT107 may improve responses to PD-L1 inhibition. To test this hypothesis, we designed a randomized trial (NCT03513952) in mUC comparing the combination of CYT107 and atezolizumab to atezolizumab alone. Methods: Patients with ECOG PS ≤2 and RECIST v1.1 measurable mUC with disease recurrence after platinum-based chemotherapy are eligible. A safety run-in of 6 patients with staggered enrollment to atezolizumab plus CYT107 will be followed by randomization if <2 patients experience a DLT. An additional 48 patients will then be randomized 1:1 to atezolizumab 1200 mg IV q3wks with or without CYT107 10 ug/kg IM qwk X 4, started 1 wk before atezolizumab. The primary endpoint is RECIST v1.1 ORR, with H0 14.8% and HA 45%, one-sided α 0.10; power 88%. An interim futility analysis will be performed after 24 randomized patients have their first disease assessment; cessation of the trial will occur if an O’Brien-Fleming futility boundary of <-0.0063 in the ORR scale is observed between the experimental and control arm. Secondary endpoints include clinical benefit rate, PFS, DOR, OS, results by PD-L1 expression stratification, and safety. Exploratory correlative evaluations of tumor-infiltrating immune cells, interferon γ expression, inflammatory gene expression, ELISPOT, T cell receptor sequencing, serum metabolite levels, gut microbiome, and PK analyses will be performed. Current state: Trial accrual has begun and is anticipated to complete around mid-2020. Clinical trial information: NCT03513952.
A phase III randomized open label study comparing bempegaldesleukin (NKTR-214) plus nivolumab to sunitinib or cabozantinib (investigator's choice) in patients with previously untreated advanced renal cell carcinoma.
Authors: Tannir Nizar M. , Agarwal Neeraj , Pal Sumanta K. , Formiga Maria Nirvana , Guo Jun , George Daniel J. , Tagliaferri Mary Ann , Hannah Alison L. , Zhang Jenny Yanzhen , O'Keeffe Bridget A. , Cho Daniel C. 
Published: May 2019

TPS4595 Background: Bempegaldesleukin (NKTR-214) is a CD122-preferential IL-2 pathway agonist that stimulates proliferation and activation of tumor antigen-specific CD8+ T cells and natural killer cells within the tumor microenvironment and increases PD-1/PD-L1 expression. These properties make bempegaldesleukin (NKTR-214) a potentially promising agent for combination therapy with checkpoint inhibitors that target and inhibit the PD-1/PD-L1 pathway. In phase 1 studies, NKTR-214 plus nivolumab demonstrated encouraging objective response rates (ORR) in first-line renal cell carcinoma (RCC) and an acceptable safety profile. Immunotherapy with NKTR-214 plus nivolumab may lead to greater clinical benefit than tyrosine kinase inhibitors (TKIs), standard-of-care agents, in this patient population. Methods: This multicenter, randomized, open-label phase 3 study (NCT03729245) will evaluate the efficacy and safety of bempegaldesleukin (NKTR-214) plus nivolumab compared with investigator’s choice of TKI (sunitinib or cabozantinib) in patients with previously untreated advanced or metastatic RCC with clear cell component. Exclusion criteria include active brain metastasis and autoimmune disease. Approximately 600 patients will be randomized in a 1:1 ratio, stratified by PD-L1 status (≥1% vs < 1% or indeterminate), International Metastatic RCC Database Consortium prognostic score (1-2 [intermediate risk] vs 3-6 [poor risk]); and TKI (sunitinib or cabozantinib; cabozantinib percentage to be capped at 50%). Combination therapy will consist of bempegaldesleukin (NKTR-214) 0.006 mg/kg intravenously (IV) every 3 weeks (Q3W) plus nivolumab 360 mg IV Q3W until progression or death or maximum of 2 years. TKI therapy will consist of sunitinib 50 mg orally once daily (QD) for 4 weeks followed by 2 weeks off or cabozantinib 60 mg orally QD. Primary objectives are ORR by blinded independent central radiology (BICR) assessment and overall survival. Secondary objectives are progression-free survival by BICR, safety, predictive value of PD-L1 expression, and quality of life. Enrollment is ongoing. Clinical trial information: NCT03729245.
PROSPER: A phase III randomized study comparing perioperative nivolumab (nivo) versus observation in patients with renal cell carcinoma (RCC) undergoing nephrectomy (ECOG-ACRIN 8143).
Authors: Harshman Lauren Christine , Puligandla Maneka , Haas Naomi B. , Allaf Mohamad , Drake Charles G. , McDermott David F. , Signoretti Sabina , Cella David , Gupta Rajan T. , Shuch Brian M. , Choueiri Toni K. , Lara Primo , Kapoor Anil , Heng Daniel Yick Chin , Jewett Michael A.S. , Master Viraj A. , Michaelson M. Dror , Leibovich Bradley C. , Maskens Deb , Carducci Michael Anthony ,   On Behalf of the PROSPER RCC Investigators
Published: May 2019

TPS4597 Background: The anti-PD-1 antibody nivo improves overall survival (OS) in metastatic RCC and is well tolerated. There is no standard adjuvant (adjuv) systemic therapy that increases OS over surgery alone for non-metastatic RCC. Priming the immune system prior to surgery with anti-PD-1 has shown an OS benefit compared to a pure adjuv approach in mouse solid tumor models. Multiple ph 2 studies in bladder, lung and breast cancers have shown remarkable pathologic responses with neoadjuvant (neoadj) PD-1 blockade. Two ongoing ph 2 studies of perioperative nivo in M0 RCC patients are showing preliminary feasibility and safety with no surgical delays (NCT02575222; NCT02595918). PROSPER RCC (NCT03055013) aims to improve clinical outcomes by priming the immune system prior to nephrectomy with neoadj nivo and continued engagement with adjuv blockade in patients with high risk RCC compared to surgery alone. Methods: This global, unblinded, phase 3 National Clinical Trials Network study is currently accruing patients with clinical stage ≥T2 or TanyN+ RCC of any histology planned for nephrectomy. Oligometastases are permitted if can be rendered NED. We amended the study to enhance accrual and patient quality of life by changing nivo dosing to 480mg q4 wks and requiring baseline tumor biopsy only in the nivo arm. The investigational arm receives 1 dose of nivo prior to surgery followed by 9 adjuv doses. The control arm undergoes standard nephrectomy followed by observation. Randomized patients are stratified by clinical T stage, node positivity, and M stage. Accrual of 805 patients provides 84.2% power to detect a 14.4% absolute benefit in recurrence-free survival (RFS) at 5 years assuming the ASSURE historical control of ~56% to 70% (HR = 0.70). The study is powered to evaluate a significant increase in OS (HR 0.67). Critical perioperative therapy considerations such as safety, feasibility, and quality of life endpoints have been integrated. PROSPER RCC embeds a wealth of translational work aimed at investigating the impact of the baseline immune milieu, the changes induced by neoadjuvant anti-PD-1 priming, and how both may predict clinical outcomes. Clinical trial information: NCT03055013.