bluuebunny/crossref_metadata_2025_split huggingface dataset:
bTMB-High Basket trial: A multicenter phase II trial of nivolumab monotherapy in patients with advanced gastrointestinal cancers with high blood tumor mutational burden (bTMB).
Authors: Nakamura Yoshiaki , Komatsu Yoshito , Kato Ken , Shinozaki Eiji , Bando Hideaki , Kato Takeshi , Nishina Tomohiro , Esaki Taito , Nomura Shogo , Ogawa Gakuto , Sugama Ayako , Fukutani Miki , Sato Akihiro , Odegaard Justin , Kuwata Takeshi , Matsushima Kouji , Nakatsura Tetsuya , Nakajima Hiromichi , Yoshino Takayuki 
Published: January 2019

TPS179 Background: Tumor mutational burden (TMB) is an emerging biomarker for immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). Analysis of circulating tumor DNA (ctDNA) has been reported to effectively identify patients likely to respond to ICIs by effectively and non-invasively evaluating the TMB in the tumor in NSCLC and gastric cancer. Methods: We are conducting an investigator-initiated multicenter phase II basket trial to investigate efficacy and safety of nivolumab monotherapy in patients with advanced gastrointestinal (GI) cancers with high bTMB identified by ctDNA analysis as part of the Nationwide Cancer Genome Screening Project (SCRUM-Japan GI-SCREEN). Eligibility criteria include histologically confirmed unresectable or recurrent GI malignancies; ECOG PS of 0 or 1; refractory or intolerant to the standard therapies; and high bTMB identified by a 73-gene sequencing ctDNA panel (Guardant360) regardless of microsatellite instability status. Patients will be enrolled into one of four disease-specific cohorts (colorectal, gastric, esophageal, and other GI cancer cohort), and receive intravenous nivolumab monotherapy of 360 mg every 3 weeks. The bTMB score is calculated by adjustment of mutation count by tumor fraction, and tentative bTMB level cut-offs were determined according to objective response rate (ORR) reported for ICI treatment for each tumor subtype in previous trials. The trial will utilize a two-stage design with a Bayesian hierarchical model, and tentative bTMB level cut-off will be re-assessed in the first stage. Primary endpoint in each stage is the disease control rate at 6 week and the ORR assessed by investigators per RECIST v1.1, respectively. Target sample size is determined as 70 in total so that the statistical power in each disease-specific cohort calculated based on a Bayesian posterior distribution attains 70 to 80% with one-sided alpha level in each cohort of approximately 10%. For biomarker analysis, tumor tissue and ctDNA will be serially collected and analyzed by whole-exome, transcriptome, and T cell receptor sequencing. This trial was initiated since September 2018. Clinical trial information: UMIN000033182.
Phase I/II trial of perioperative avelumab in combination with chemoradiation in the treatment of stage II/III resectable esophageal cancer.
Authors: Uboha Nataliya Volodymyrivna , Maloney James D. , McCarthy Daniel , Deming Dustin A. , LoConte Noelle K. , Matkowskyj Kristina , Eickhoff Jens C. , Mulkerin Daniel , DeCamp Malcolm M. , Lubner Sam Joseph , Turk Anita Ahmed , Bassetti Michael Frederick 
Published: January 2019

TPS181 Background: Neoadjuvant chemoradiation (CRT) followed by resection is the standard treatment for patients with stage II and III esophageal cancer. However, about 50% of patients develop recurrent disease after treatment completion. Patients with residual disease at the time of resection (~ 75%) and especially those with persistent lymph node involvement have the worst prognosis. Hence, novel strategies are needed to improve outcomes. A number of preclinical and clinical studies demonstrated synergism between radiation and immunotherapy. In esophageal cancers, CRT has been shown to alter tumor microenvironment with upregulation of PD-L1 expression and increase in CD8+ T lymphocyte infiltration. Immune checkpoint inhibitors have demonstrated promising activity in metastatic gastroesophageal cancer. Utilizing these agents in earlier disease stages and combining with chemoradiation may increase their efficacy by taking advantage of potential synergism with radiation. This trial will evaluate safety and efficacy of avelumab in combination with CRT in resectable esophageal cancer. Methods: This is a two-part phase I/II clinical trial evaluating safety and efficacy of perioperative avelumab plus CRT in patients with resectable esophageal cancer. This trial will enroll a total of 24 subjects with untreated resectable esophageal cancer (including gastroesophageal junction). Part 1 will be a run-in phase that enrolls 6 patients for safety evaluation. Part 2 will enroll 18 additional patients for efficacy and additional safety evaluation. The primary endpoint for the phase II component is the pathological complete response rate. Subjects will receive neoadjuvant radiation (41.4 Gy in 23 fractions) with weekly carboplatin (AUC 2) and paclitaxel (50 mg/mg2). Three doses of avelumab (10 mg/kg, every 14 days) will be administered starting on day 29 of treatment, to coincide with the last chemotherapy dose. Esophagectomy will be performed ~ 8 weeks after CRT completion. Subjects will receive 8 doses of avelumab after resection. This study is actively enrolling patients at University of Wisconsin. Clinical trial information: NCT03490292.
HGCSG 1603: Phase II study of ramucirumab and irinotecan combination therapy as second-line treatment in patients with metastatic or advanced gastric cancer.
Authors: Ishiguro Atsushi , Kawamoto Yasuyuki , Yuki Satoshi , Kobayashi Yoshimitsu , Harada Kazuaki , Sogabe Susumu , Tsuji Yasushi , Nakano Shintaro , Sawada Kentaro , Muranaka Tetsuhito , Nakatsumi Hiroshi , Dazai Masayoshi , Sasaki Takahide , Eto Kazunori , Nakamura Michio , Muto Osamu , Sakata Yuh , Sakamoto Naoya , Komatsu Yoshito 
Published: January 2019

TPS183 Background: As second-line chemotherapy for gastric cancer, a survival benefit has been shown in several clinical trials. Irinotecan and taxanes are recommended as second-line regimen. However, therapeutic outcomes have remained unsatisfactory and more effective treatment are expected. Ramucirumab (RAM) is a fully human IgG1 monoclonal vascular endothelial growth factor receptor-2 (VEGFR-2) antibody that prevents ligand binding of VEGF-A, VEGF-C, and VEGF-D and the receptor-mediated pathway activation in endothelial cells, subsequently inhibiting neovascularization. In the REGARD study, RAM monotherapy for previously treated advanced gastric or gastro-esophageal junction adenocarcinoma improved median overall survival (mOS) compared with placebo. Moreover, in the RAINBOW study, RAM plus paclitaxel (PTX) versus placebo plus PTX, mOS showed significantly longer in RAM plus PTX group than in placebo plus PTX group. In contrast, there are no data on the efficacy of RAM and irinotecan in the second-line treatment for gastric cancer. The WJOG 4007 study demonstrated an equivalent efficacy between irinotecan and PTX. In this study, we propose to examine the efficacy of RAM plus irinotecan. Methods: This study is carried out as a multicenter, non-randomized, single arm, prospective, phase II study. The patients with metastatic or advanced gastric cancer that is refractory or intolerance to primary chemotherapy are eligible for this study. RAM and irinotecan combination therapy is administered every two weeks, which is continued until progression or emergence of adverse events requiring discontinuation. The primary endpoint is progression-free survival rate at six months, and the secondary endpoints are OS, progression-free survival, response rate, safety, and dose intensity for each drug. A total of 35 cases areplanned for registration. This study is registered with the University Hospital Medical Information Network. Clinical trial information: UMIN000030372.
GA CPI 613: A single arm, open-label phase I study of CPI-613 in combination with gemcitabine and nab-paclitaxel for patients with locally advanced or metastatic pancreatic cancer.
Authors: Alistar Angela Tatiana , Morris Bonny , Harrison Lawrence , Bickenbach Kai , Ginder Nancy , Proulx Jonathan , McIlwain Laura , Luther Sanjeev 
Published: January 2019

TPS459 Background: Pancreatic cancer is the third leading cause of cancer death in the USA. The most effective treatments for first-line metastatic pancreatic cancer are FOLFIRINOX and gemcitabine plus nab-paclitaxel, which provide a median overall survival of 11·1 months and 8·5 months with moderate toxicity. Safer and more effective treatments are needed. The glycolic and mitochondrial metabolism are aberrant in pancreatic cancer and translate into chemoresistance. Inhibition of glutamine metabolism can potentially synergize with therapies that increase intracellular reactive oxygen species such as Nab-Paclitaxel. CPI- 613 is a novel antimitocondrial developed by Rafael Pharmaceuticals that showed preclinical activity in pancreatic cancer cell lines as well as promising clinical activity in combination with modified FOLFIRINOX in patients with stage IV pancreatic cancer. Preclinical data suggests possible synergy of CPI- 613 with nab-paclitaxel. Methods: This is a single arm, open-label, nonblinded phase I study of CPI-613 in combination with gemcitabine and nab-paclitaxel in patients with locally advanced or metastatic pancreatic cancer. Key eligibility criteria include: histologically or cytologically documented and measurable locally advanced or metastatic pancreatic adenocarcinoma, ECOG performance status 0-2, first line treatment for both locally advanced or metastatic. CPI-613 will be infused intravenously with a starting dose of 500 mg/m2 followed by 125 mg/m2 nab-paclitaxel and 1,000 mg/m2 gemcitabine on day 1, 8, 15 of a 28-day cycle. The study is comprised of a two-stage dose-escalation schema to evaluate the MTD of CPI-613. At least six months of treatment is planned for patients who have a response. Primary endpoint of the study is MTD of CPI 613 when combined with gemcitabine and nab-paclitaxel and secondary endpoints of the study are treatment related adverse events, CR and PR. This study was initiated in February 2018 at Atlantic Health System and within first seven months of the study, 11 out of 24 planned patients have been enrolled. Clinical trial information: NCT03435289.
Precision-Panc Master Protocol: Personalizing treatment for pancreatic cancer ISRCTN14879538—Part of Precision-Panc United Kingdom.
Authors: Valle Juan W. , Evans T.R. Jeffry , McKay Colin J , Dixon-Hughes Judith , Paul James , Stobo Jamie , Cooke Susie , Willshire Christine , Williams Nicola , Duthie Fraser , Biankin Andrew , Chang David Kuang-Fu 
Published: January 2019

TPS460 Background: A major challenge of lower incidence cancer types is that to make significant advances a network approach is required to coordinate research, generate greater clinical capacity and recruit sufficient patients. This is particularly the case for pancreatic cancer (PC). To address this, we established Precision-Panc, a synergistic and dynamic platform aligning “discovery”, “preclinical” and “clinical” therapeutic development. Methods: Central to the clinical development is the Precision-Panc Master Protocol, a multi-centre “portal” protocol recruiting patients with known or suspected PC, to enable enrolment into PRIMUS (Pancreatic canceR Individualised Multi-arm Umbrella Study), examining different treatment regimens and/or biomarker development. Eligible patients are identified prior to the diagnostic biopsy to obtain Stage 1 (Screening) Consent for extra tissue to be taken in the same biopsy setting. Patients who already have a diagnosis are asked to provide additional research biopsy. Once the PC diagnosis is made, Stage 2 (Registration) Consent is obtained for molecular profiling at the central reference laboratory using Precision-Panc NGS Diagnostic (bespoke clinical grade assay), including germline testing of 12 PC predisposition genes. The results may inform eligibility for a PRIMUS study. There is no sample size calculation due to the nature of the Master Protocol; however, individual PRIMUS studies will be appropriately powered according to their study design and primary endpoint. Results: Adults (aged >16 years) with either a hypodense pancreatic mass highly suspicious of PC (+/- distant metastases) or histologically/cytologically confirmed PC and its variants; willing and able to undergo tumour biopsy to obtain sufficient tissue for molecular profiling; deemed suitable to receive chemotherapy and/or radiotherapy and/or surgery pending stage of disease; must give both Stage 1 and 2 informed consent. Conclusions: The study opened on 28 Dec 2017; by 25 Sep 2018, 67 patients have been screened for Precision-Panc, 43 of whom have gone on to be registered and 19 have then been randomised to the PRIMUS-001 study (first-line metastatic). Clinical trial information: ISRCTN14879538.
Trial design for a phase 3 study evaluating pemigatinib (INCB054828) versus gemcitabine plus cisplatin chemotherapy in first-line treatment of patients with cholangiocarcinoma with FGFR2 rearrangement.
Authors: Bekaii-Saab Tanios S. , Valle Juan W. , Borad Mitesh J. , Melisi Davide , Vogel Arndt , Féliz Luis , Lihou Christine Francis , Zhen Huiling , Abou-Alfa Ghassan K. 
Published: January 2019

TPS462 Background: Dysregulation of fibroblast growth factor receptor (FGFR) signaling by FGFR genetic alterations is implicated in many cancers, including cholangiocarcinoma (CCA). FGFR2 translocations with fusion partners occur in ≈10% to 20% of intrahepatic CCA tumors. Pemigatinib is a selective oral inhibitor of FGFR-1, 2, 3. Preliminary data from the ongoing phase 2 study show efficacy and tolerable safety in patients (pts) with CCA with FGFR2 translocations. We present the design for a phase 3, open-label, randomized trial investigating pemigatinib monotherapy versus gemcitabine plus cisplatin chemotherapy in the first-line treatment of pts with advanced/metastatic or unresectable CCA with FGFR2 rearrangement. Methods: Eligible pts (target, N = 432) are ≥ 18 years (≥ 20 years for Japanese pts) and have ECOG performance status ≤ 1 and histologically confirmed advanced (locally advanced, metastatic, or recurrent) CCA with a documented FGFR2 rearrangement. Key exclusion criteria include prior systemic therapy, excluding adjuvant/neoadjuvant treatment completed ≥ 6 months before enrollment; current evidence of clinically significant corneal or retinal disorder; history of calcium and phosphate homeostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues; and known, untreated CNS metastases or history of uncontrolled seizures. Pts are randomized 1:1 and stratified by geographic region and tumor burden into 2 treatment groups: pemigatinib starting dose 13.5 mg once daily continuously on a 3-week cycle; or gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) administered intravenously on days 1 and 8 of every 3-week cycle for up to 8 cycles until disease progression or unacceptable toxicity. Crossover to pemigatinib may be allowed once progressive disease is confirmed. The primary endpoint is progression-free survival (based on independent central review using RECIST v1.1). Secondary endpoints include overall response rate, overall survival, duration of response, disease control rate, safety and tolerability, and impact on quality of life. Clinical trial information: NCT03656536.
Celiac plexus radiosurgery for pain management in advanced cancer patients: An international phase II trial.
Authors: Lawrence Yaacov Richard , Meron Tikva , Dicker Adam P. , Zimmermann Camilla , Ben-Ayun Maoz , Hausner David , Golan Talia , Morag Ofir , Ackerstein Aliza , Pfeffer Raphael M. , Dawson Laura A. , Shlomo Nir , Ohri Nitin , Narayana Ashwatha , Gaya Andrew , Diaz Pardo Dayssy Alexandra , Yanovsky Inessa , Fluss Ronen , Freedman Laurence S , Symon Zvi 
Published: January 2019

TPS466 Background: Many cancer patients, especially those with pancreatic cancer, suffer from severe back/epigastric pain. Contemporary approaches (opioids, celiac blocks, systemic chemotherapy) are often inadequate. This clinical trial investigates a new approach in which high-dose radiation (radiosurgery) is focused on the retroperitoneal celiac plexus nerve bundle. Preliminary results from a single institution pilot trial NCT02356406 are promising: pain relief is substantial and side effects minimal. The main aim of the trial is to establish safety/efficacy in the setting of an international multicenter study. Exploratory analyses will examine the relationship between pain reduction and subjects’ quality-of-life, functionality, and caregiver burden. Methods: Eligibility criteria include a diagnosis of metastatic/unresectable malignancy, uncontrolled pain defined as ≥ 5 on 11-point BPI-SF scale despite analgesic use, typical retroperitoneal pain syndrome, prognosis > 8 weeks, ECOG 0-2, anatomical involvement of the celiac plexus (e.g. any pancreatic cancer, or any other cancer involving the celiac trunk). Exclusion criteria include previous upper abdo. radiation. The intervention consists of a single 25 Gy radiation fraction delivered to the celiac plexus, using anterolateral aspect of the aorta from the 12th thoracic to 2nd lumbar vertebral body as a surrogate structure. The primary tumour may be irradiated at physicians’ discretion. Dose-painting technique limits dose to organs at risk. Pain intensity will be measured using Brief Pain Inventory Short Form (BPI-SF), and quality of life with FACT-Hep. The primary endpoint is complete or partial pain response, defined as a decrease between the score immediately before treatment and 3 weeks’ post-treatment. A change of two or more on the BPI 11-point pain scale is defined as clinically significant. Secondary endpoints include other BPI pain endpoints, pain at 6 weeks, analgesic use, toxicity (CTCAE v4.03), quality of life and functional measures. Analgesia is not restricted. Expected accrual is 100 subjects over three years. Supported by Gateway for Cancer Research, additional support from Israel Cancer Association. Clinical trial information: NCT03323489.
A phase Ib trial of anti-VEGFR/PDGFR vorolanib combined with immune checkpoint inhibitors (CPIs) in solid tumors.
Authors: Bagegni Nusayba Ali , Tan Benjamin R. , Park Haeseong , Kraft Katlyn , Amin Manik A. , Lim Kian-Huat , Morgensztern Daniel , Pedersen Katrina , Suresh Rama , Trikalinos Nikolaos , Wang-Gillam Andrea 
Published: January 2019

TPS472 Background: Immune CPIs have become a standard treatment option for many advanced malignancies, including gastric (G)/GE junction (GEJ) and hepatocellular cancer (HCC), but resistance is inevitable. Data suggests angiogenesis plays a key role in tumor-mediated immune regulation. Vascular endothelial growth factor (VEGF) can inhibit intra-tumor T cell trafficking, while anti-VEGF therapy can improve T cell infiltration, potentially enhancing response to CPIs to overcome resistance. Vorolanib (V), a potent oral VEGFR/PDGFR inhibitor, has anti-angiogenic properties with a favorable toxicity profile. This phase 1b study is aimed to assess the safety and efficacy of V + CPIs, pembrolizumab (P) or nivolumab (N), in pts with advanced solid tumors. Methods: The primary objective is to determine the recommended phase 2 dose (RP2D) of V + CPIs. Secondary objectives include safety, toxicity and objective response rate (ORR) and survival outcomes. Correlatives include analysis of angiogenic factors and tumor infiltrating lymphocytes as response biomarkers in archived tumor tissue and peripheral blood. Key eligibility for dose escalation cohort includes pts with solid tumors who can receive standard P or N, and for dose expansion cohort includes pts with PD-L1+ G/GEJ cancer who progressed on one or two lines of chemo, refused or are not candidates for chemo; or HCC Child-Pugh A treated with or refused sorafenib, ECOG PS 0-1 and adequate organ function. Key exclusions include prior CPI, significant bleeding, thrombosis, autoimmune disease or condition requiring corticosteroid use. A 3+3 design will be utilized to determine maximum tolerated dose and RP2D. V starts at 300 mg PO daily, pts receive N 480 mg IV Q 28-day cycle or P 200 mg IV Q 21-day cycle (max 36 pts). Dose level advancement occurs when all pts complete cycle 1 of assessed level. 20 additional pts (10 HCC, 10 G/GEJ cancer) will be treated at RP2D. Response assessment by RECIST v1.1 occurs Q 3 cycles on P or Q 2 cycles on N. ORR of 20% or greater warrants further investigation. Enrollment is ongoing. Clinical trial information: NCT03511222.
A phase II, open-label pilot study evaluating the safety and activity of nal-IRI in combination with 5-FU and oxaliplatin in preoperative treatment of pancreatic adenocarcinoma (NEO-Nal-IRI study).
Authors: Parekh Hiral D. , DeRemer David L. , Hitchcock Kathryn , McGorray Susan P. , Allegra Allison , Daniels Alisha , Fan Z. Hugh , Allegra Carmen Joseph , Zlotecki Robert , Hughes Steven J. , Cioffi Jessica L , Trevino Jose Gilberto , George Thomas J. 
Published: January 2019

TPS476 Background: Neoadjuvant treatment for borderline resectable pancreatic cancer (PCa) is increasing in acceptability, but a standard regimen has yet to be established. Multiple studies have demonstrated feasibility and effectiveness of the FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen in the perioperative setting. However, FOLFIRINOX often requires dose modifications, delays and growth factor support due to excessive toxicity which can complicate care delivery when given neoadjuvantly. Irinotecan liposomal injection (Nal-IRI) is FDA approved with a very tolerable safety profile in refractory metastatic PCa. The current study aims to substitute Nal-IRI for traditional irinotecan in the standard FOLFIRINOX regimen and demonstrate safe and effective delivery in the neoadjuvant setting. Methods: This phase II, open-label, single-arm study targets patients with borderline resectable PCa without metastatic disease. Other key eligibility criteria include age ≥ 18 years, measurable disease by RECIST v1.1, adequate cardiac, renal, hepatic function, and Eastern Cooperative Oncology Group performance status of 0 to 1. Patients receive FOLFNal-IRINOX regimen as per table every two weeks for four months followed by disease reassessment. Patients who remain surgical candidates will undergo surgical resection within four to eight weeks following last dose of therapy. The primary endpoint is to assess safety and feasibility of regimen in perioperative setting. Secondary endpoints include R0 resection rate, clinical, biochemical and radiological response rate and patient-reported quality of life as measured by the NCI validated FACT-G scale. Enrollment continues to a maximum of 28 evaluable patients to demonstrate a reduction in historical 30 day postoperative complication rate. FOLFNal-IRINOX regimen. Clinical trial information: NCT03483038. [Table: see text]