bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-invasive volatile organic compound analysis from exhaled breath for the diagnosis of gastroesophageal cancer.
Authors: Markar Sheraz , Hanna George 
Published: February 2017

TPS225 Background: The work carried out in our laboratory using Selective Ion Flow-Tube Mass Spectrometry (SIFT-MS) analysis of volatile organic compounds (VOCs) in exhaled breath has identified compounds that can differentiate gastro-esophageal cancer from non-cancer patients. A model has been developed based on 220 patients with upper gastrointestinal pathology (81 cancer, 88 positive control and 51 patients with endoscopically normal gastrointestinal tract). Methods: Clinical trial registry number: 14/LO/1136. Study 1: Refinement of VOC exhaled breath model. Exhaled breath from 120 patients undergoing diagnostic lower endoscopy for the investigation of gastrointestinal symptoms will be used to refine the existing model by studying the influence of lower gastrointestinal diseases and in particular colorectal cancer, upon VOC analysis. To date 94 patients have been recruited. Study 2: Blinded validation multi-centre study for the use of exhaled Breath SIFT-MS analysis to predict gastro-esophageal cancer. This study will be conducted across four centers and will utilize SIFT-MS exhaled breath analysis, for comparison of predicted cancer risk based upon the VOC exhaled breath model compared to endoscopic findings and histology biopsies in order to determine the overall diagnostic accuracy for this non-invasive test. Sample Size – Based upon a prevalence of cancer of 50% in the study population and maintaining a sensitivity and specificity of 80% for the diagnostic model derived from our previous research, the sample size estimated is 325 patients. Inclusion criteria:Patients with upper gastrointestinal symptoms attending for endoscopy or surgery. Exclusion criteria: Patients with a documented active infection or liver disease. Statistical methods: Comparison of predicted cancer risk and actual OGD findings or histology from endoscopic biopsies will then be made, and the overall diagnostic accuracy (sensitivity, specificity, positive and negative predictive value, ROC curve analysis) for this non-invasive diagnostic investigation will be determined. Deliverables: The diagnostic accuracy of the exhaled breath test for the prediction of oesophago-gastric cancer. Clinical trial information: 14/LO/1136.
Optimal prophylactic method of venous thromboembolism for gastrectomy in Korean patients: A prospective randomized trial.
Authors: Song Kyo Young 
Published: February 2017

TPS229 Background: Whereas routine prophylaxis for venous thromboembolism (VTE) is frequently utilized in the West, Asian physicians employ it much less often, based on its recorded rarity amongst their patients. This trial is to examine the incidence of VTE and to determine the optimal method of thromboembolic prophylaxis following gastrectomy for cancer. Methods: In this prospective randomized trial, patients will be assigned to either an intermittent pneumatic compression (IPC) only or an IPC plus enoxaparin. The primary end point of this study is to determine the VTE incidence rate within 30 days of surgery. A history with physical examinations for VTE and a serum d-dimer test is scheduled on postoperative days (POD) 0, 1, 4, and 7. Duplex ultrasonography (DUS) was performed as an objective test for deep vein thrombosis at POD 4. The number of patients to be randomized was calculated to be 682. Clinical trial information: NCT01448746.
A phase IIb, randomized, controlled, multicenter, open-label study of the efficacy and immune response of GVAX pancreas vaccine and CRS-207 compared to chemotherapy or to CRS-207 alone in adults with previously treated metastatic pancreatic adenocarcinoma (ECLIPSE Study).
Authors: Le Dung T. , Wang-Gillam Andrea , Picozzi Vincent J. , Crocenzi Todd S. , Morse Michael , Zeh Herbert , Fine Robert Lance , Murphy Aimee , Skoble Justin , Lemmens Ed , Ferber Sandy , Rosen Allan , Grous John J. , Dubensky Thomas , Brockstedt Dirk G. , Lutz Eric , Jaffee Elizabeth M. 
Published: February 2017

TPS489 Background: A prime-boost vaccination strategy using GVAX pancreas vaccine and CRS-207 is showing activity in patients with metastatic pancreatic adenocarcinoma (PDA). GVAX is composed of lethally-irradiated, allogeneic pancreatic cancer cells modified to express GM-CSF. GVAX induces a response against multiple tumor antigens and is given after low-dose cyclophosphamide (CY) to inhibit regulatory T cells. CRS-207 is live-attenuated Listeria monocytogenes engineered to express the tumor-associated antigen mesothelin. CRS-207 boosts responses against mesothelin and stimulates both innate and adaptive immunity by activating T cells and NK cells. Results from a phase 2 study demonstrated CY/GVAX plus CRS-207 improved overall survival (OS) compared to CY/GVAX alone (p-value<0.05; Le, GI ASCO 2014). Methods: This is a phase 2b study comparing CY/GVAX and CRS-207 to chemotherapy or to CRS-207 alone in patients with previously-treated metastatic PDA. Patients will be enrolled in two cohorts: 150 patients into a primary cohort of patients with at least two prior chemotherapy regimens for metastatic disease (third + line) and 90 patients into an exploratory cohort of patients with only one prior chemotherapy regimen for metastatic disease (second line). Patients will be randomized in a 1:1:1 ratio to receive 2 doses of CY/GVAX and 4 doses of CRS-207 (Arm A), six doses of CRS-207 (Arm B) or physician’s choice of single-agent chemotherapy (Arm C). The primary objective is to compare OS between Arms A and C in the primary cohort. Secondary/exploratory objectives include: comparison of OS in both primary and exploratory cohorts between all treatment arms, assessment of safety and clinical responses (tumor assessments and CA19-9 levels) and correlation of Lm- and mesothelin-specific T cell and other immunological responses with clinical responses. Updated enrollment will be reported. (Sponsor: Aduro BioTech, Inc.; NCT02004262). Clinical trial information: NCT02004262.
Treatment and underlying mechanisms of pancreatic cancer cachexia (PANCAX study).
Authors: Khanuja Jasleen , Gresham Gillian , Osipov Arsen , Tuli Richard , Hendifar Andrew Eugene 
Published: February 2017

TPS491 Background: Advanced pancreatic adenocarcinoma is characterized by progressive weight loss and nutritional deterioration, resulting in a cachexia-anorexia syndrome. This wasting has been linked to poorer survival, alterations in host defenses, and decreased functional ability and quality of life. Gut microbiota alterations affect muscle composition and have been demonstrated in mouse models of cancer cachexia. The relationship between pancreatic cancer cachexia and the composition of the fecal microbiome will be investigated. We propose the first prospective study of peptide-based enteral nutritional support in cachectic advanced pancreatic adenocarcinoma patients undergoing chemotherapy. We aim to establish the feasibility and efficacy of enteral nutrition as measured by changes in weight, lean body mass, and hand-grip strength. We will also explore the relationship between anorexia-cachexia with gut hormone changes and alterations in the fecal micro-biome, which may account for resultant malnutrition and muscle loss. Methods: Eligible patients will have a diagnosis of both pancreatic adenocarcinoma and cachexia, defined as greater than 5% unintentional weight loss within the previous 6 months. Peptamen 1.5 will be administered via a jejunal tube for 12 weeks. Lean body mass, evaluated by DEXA, and weight will be assessed at predefined intervals. Oral food intake will measured by 24 hour food recall and a taste and smells alteration survey. Secondary outcomes including, response to chemotherapy, survival, and quality of life will be studied. Fecal microbiome, serum inflammatory markers, and gut hormone levels will be assessed at pre-defined intervals. We have received funding from NIH/NCATS Grant # UL1TR000124 and opened enrollment in September 2014.
A randomized, open-label, phase I/II trial of gemcitabine plus nab-paclitaxel with or without FG-3019 as neoadjuvant chemotherapy in locally advanced, unresectable pancreatic cancer.
Authors: Rocha Flavio G. , Helton Scott , Picozzi Vincent J. 
Published: February 2017

TPS500 Background: Only 15% of patients with pancreatic ductal adenocarcinoma (PDAC) are eligible for resection. Patients with locally advanced PDAC may become candidates for surgery following donwstaging with neoadjuvant therapy. PDAC often exhibits a high degree of desmoplasia, characterized by extensive connective tissue stroma. FG-3019 is a recombinant human monoclonal antibody that binds to connective tissue growth factor and significantly reduces tumor growth, neovascularization, and metastases in mouse models of PDAC. Therefore, FG-3019 may change the fibrotic character of PDAC to one more amenable to resection. In a phase I trial of stage III/IV patients, FG-3019 did not add toxicity when combined with gemcitabine and erlotinib. Methods: Phase 1/2, randomized, open-label trial to evaluate safety and tolerability of gemcitabine plus Nab-paclitaxel with FG-3019 or gemcitabine plus Nab-paclitaxel in subjects with locally advanced, unresectable PDAC (clinicaltrials.gov #NCT02210559). Primary endpoint is treatment-related adverse events. Secondary endpoints include R0 resection rate, surgical complications, tumor response, and survival. Patients with biopsy-proven PDAC are included following radiographic and laparoscopic confirmation of irresectability and no metastases. Sample size of 40 is based on clinical judgment for initial exploration of safety, tolerability, and treatment effect. Each cycle is 28 days and subjects receive up to six cycles of treatment. Those who complete treatment undergo resection based on the following criteria: reduction in CA 19-9 level by more than 50%, FDG-PET SUVmax decrease by >30%, or radiological tumor response per RECIST to meet the definition of resectable or borderline resectable. Safety will be assessed through adverse event monitoring, clinical laboratory testing, ECG, ECOG performance status, vital signs, and physical exam until 28 days after the last FG-3019 infusion. All resected subjects will be followed for 30 days after discharge and undergo safety assessment per standard of care. Since the trial opened in 8/2014, we have enrolled 1/40 patients. Clinical trial information: NCT02210559.
Treatment of neuroendocrine tumors (NETs) with combination of everolimus and lu-177 radiolabeled somatostatin analogue.
Authors: Aljubran Ali Husain , Tuli Mahmoud , Raef Hussein 
Published: February 2017

TPS502 Background: Treatment of Grade 1 and 2 NET is complex and involves surgical, Locoregional and systemic modalities depending on the manifestations as well as extent of disease. Of the emerging new systemic modalities are everolimus and radiolabelled somatostatin analogue. everolimus is FDA approved for advanced pancreatic NET whereas radiolabelled somatostatin analogue is still not standard therapy in the USA. However, it is gaining popularity especially in Europe as effective systemic therapy for somatostatin receptor positive tumors. Subclinical animal model research showed synergistic effect of the combination of everolimus and the Lu-177 radiolabeled somatostatin analogue. The goal of this study is to assess the safety and efficacy of the combination of Everolimus and the intravenous radiolabeled Lu-177 DOTATOC Therapy in the treatment of unresectable G1-2 neuroendocrine tumors of all gastrointestinal, lung and pancreatic origins. Methods: This is a phase 1 – 2 study. The phase 1 part involves finding the maximum tolerating dose (DLT) of everolimus and accordingly to recommend dose for the phase II part. The second part is a standard phase II trial assessing the efficacy and toxicity of the regimen at the recommended dose. A total of 30 patients will be enrolled, based on the expected response of the combination to be 20% with power of 80 and type 1 of.05, compared to the known everolimus alone overall all response of 5%. In phase 1, three patients will be treated with 5mg daily with expansion to six patients if one of the three patients experienced DLT. If DLT occurred in none of three or no more than one of six patients, everolimus dose will be escalated to 10 mg and will be considered the recommended dose for phase 2 part. Otherwise, everolimus dose will be kept at 5 mg daily and will be considered the recommended dose for phase II part. DLT in more than two of six patients will be considered unacceptable, and the trial will be closed because of high toxicity.
A phase 3 open-label, randomized, multicenter study of Imprime PGG in combination with cetuximab in patients with KRAS wild type metastatic colorectal cancer.
Authors: Huhn Richard Dale , Lowe Jamie , Grady Michele , Taitt Corina Candiani , Gargano Michele Anne , Braun Ada H. 
Published: February 2017

TPS787 Background: Imprime PGG (Imprime) is a novel immune modulator (complex carbohydrate biologic), which harnesses innate immune cells to enhance killing of antibody-targeted tumor cells. In a phase 2 single-arm clinical trial in mCRC, the combination of Imprime with cetuximab resulted in 24% ORR, 62% disease control rate (DCR), and median time to progression (TTP) of 12 wks (Tamayo ME, Ann Onc 2010), representing approximate 100% increases vs historical control (Cunningham, NEJM 2004). ORR was 45%, DCR, 82% and TTP, 24 wks in pts with KRAS WT tumors (post hoc analysis). Single-agent cetuximab has been shown to improve objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in patients (pts) with epidermal growth factor receptor (EGFR) expressing, KRAS wild-type (WT) metastatic colorectal cancer (mCRC) who failed oxaliplatin- and irinotecan-based therapy or are intolerant to irinotecan. The mechanism of action of cetuximab is thought to rely on competitive blockade of endogenous ligand binding and downstream signaling, internalization and down regulation of EGFR, as well as antibody-dependent cellular cytotoxicity (ADCC) (Erbitux SmPC). The current trial, sponsored by Biothera (registered with ClinicalTrials.gov NCT01309126) is to confirm these findings in phase 3. Methods: Eligible pts will have had prior oxaliplatin- and irinotecan-based therapy or be intolerant to irinotecan, and will meet key inclusion criteria including measurable disease and ECOG performance status of 0 or 1. In a 2:1 randomization, stratified by geographic region, prior chemotherapy and site, approximately 795 pts will receive weekly open-label Imprime plus cetuximab or cetuximab alone. The primary endpoint of the study is OS and primary analysis will occur when ~709 deaths have occurred. Secondary endpoints include PFS, ORR (based on RECIST 1.1), quality of life, safety and pharmacokinetics. Exploratory endpoints include biomarker analyses. Pt screening and enrollment is underway in the United States and Europe. Clinical trial information: NCT01309126.
E7208: A randomized phase II trial of irinotecan and cetuximab (IC) versus IC plus ramucirumab (ICR) in second line therapy of KRAS wild type colorectal cancer (CRC).
Authors: Hochster Howard S. , Catalano Paul J. , Mitchell Edith P. , Cohen Deirdre Jill , O'Dwyer Peter J. , Benson Al Bowen 
Published: February 2017

TPS793 Background: Anti-angiogenic therapy for CRC has been accepted as standard therapy with approval of bevacizumab (bev) in both first-line and second-line settings. At the time this study was started, the benefit of continuing an anti-angiogenic in second line therapy was unproven. Ramucirumab (RAM, IMC 1121b) is a humanized antibody directed against the VEGF-R2 receptor, which may prove to have different activity compared to anti-VEGF antibody (bev). Additionally, while combining the anti-EGFR antibody, cetuximab (CMAB), with bev in first-line unselected patients was not effective, it is unknown whether the same may be true with RAM plus CMAB in a second-line setting for KRAS-selected patients. Methods: The study was designed as a randomized phase II trial with 147 patients assigned to IC = irinotecan (I) 180 mg/m2 IV plus CMAB 500 mg/m2 IV q2w versus ICR = IC plus RAM 8 mg/kg IV q2w. Eligibility included prior treatment on one prior oxaliplatin and bev-containing regimen and progression within 42 days of last bev, PS 0-1, KRAS codon 12,13 wild-type and standard other chemo and bev criteria. Doses were modified for neutropenia, diarrhea, mucositis, rash and grade 3 other toxicities. The study was activated 10/8/10. The first 35 patients were enrolled and accrual was held 6/24/12 for toxicity analysis per protocol. More grade 3 events of mucositis, diarrhea, neutropenia and perforation events (including peri-rectal abscesses) were seen in the ICR arm. The study has been modified reflect the actual doses received, and now uses modified ICR (mICR) = I 150 mg/m2, CMAB 400 mg/m2 and RAM 6 mg/kg IV q2w. The study was re-activataed in May 2014. An additional 100 pts will be accrued to the revised study, giving 85% power to detect improved median PFS from 4.5 to 7.65 months. New eligibility criteria include any progression from first-line chemo (on or off), normal albumin, no bowel perforation or obstruction in last 6 months. This study is now open to accrual in ECOG-ACRIN and in SWOG with endorsement, and via CTSU. Clinical trial information: NCT01079780.
Preemptive therapy of cetuximab-induced skin rash using doxycycline, sunscreen, hydrocortisone, and moisturizer in colorectal and head and neck cancer patients.
Authors: Redman Rebecca Ann , Perez Cesar Augusto , Sledjeski Lauren , Kessans Knable Mika , Sharma Vivek R. 
Published: February 2017

TPS796 Background: Toxicities associated with the use of cetuximab include infusion reactions, dermatologic toxicity and electrolyte disturbances. Of these, skin toxicity including acneiform rash, dry skin and fissuring, paronychial inflammation, infectious sequelae and hypertrichosis occur most commonly, with acneiform rash developing in 76-88% of patients. These skin toxicities are rarely life-threatening, but they impact the quality of life of patients receiving therapy and directly affect adherence. The purpose of this study is to determine if preemptive therapy with doxycycline, sunscreen, hydrocortisone 1% cream, and moisturizer will reduce the incidence and severity of > grade 2 acneiform rash according to CTCAE v.4 in patients with colorectal and head and neck cancer receiving therapy with cetuximab. Methods: This is a single-institution, prospective, open-label, randomized study of 100 patients with colorectal and head and neck cancer receiving cetuximab in the locally advanced or metastatic setting. Those randomized to preemptive therapy will receive doxycycline 100 mg twice daily, sunscreen SPF 30, hydrocortisone 1% cream, and moisturizer beginning three days prior to the first dose of cetuximab for a duration of 8 weeks. Those randomized to standard of care will receive treatment of skin toxicity per national guidelines and treating physician discretion. Objectives are to evaluate the incidence of cetuximab-induced rash, compare the severity of cetuximab-induced rash between the preemptive treatment group and the standard care group, and monitor the toxicity of the preemptive therapy. Secondary objectives include quality of life, adherence rates, disease-specific outcomes, and survival. Patients will be evaluated at enrollment, 3 weeks into treatment and at the end of treatment for adherence, side effects and quality of life. They will be followed for up to two years for treatment outcomes and survival. With alpha of 0.05 and a power of 80%, we will be able to detect if the incidence of skin rash differs by 24% between the two groups using a two-sample one-sided binomial test. As of September 2014, 15 of 100 patients have been enrolled. Clinical trial information: NCT01874860.
A phase I study of investigational agent SGI-110 combined with irinotecan in previously treated metastatic colorectal cancer patients.
Authors: Wang Judy Sing-Zan , Gootjes Elske C. , Uram Jennifer N. , Zahurak Marianna , El-Khoueiry Anthony B. , Verheul Henk M.W. , Ahuja Nita , Azad Nilofer Saba 
Published: February 2017

TPS797 Background: Studies have suggested that epigenetic modifications may play a role in oncogenesis and acquired chemoresistance in certain cancers including colorectal cancer (CRC). Our preclinical data has shown that DNA hypermethylation may confer acquired chemoresistance, and that combining a hypomethylating agent can re-induce tumor sensitivity to irinotecan in CRC cell lines. We propose a phase I study to assess the safety and tolerability of SGI-110 with irinotecan therapy in metastatic colon cancer previously treated with irinotecan. This will be followed by a randomized phase II study to evaluate efficacy of the combination. Methods: We will enroll 12-22 patients at two institutions with metastatic colon adenocarcinoma previously treated with irinotecan to our phase I study. Dose escalation will be performed in a traditional 3+3 design, where patients receive SGI-110 30-45mg/m2 SQ days 1-5 in combination with irinotecan 125mg/m2 days 1, 8, and 15 (depending on the dose level) every 28 days, with or without G-CSF. Patients will be monitored for safety and tolerance with laboratory studies, clinical exam, and periodic CT scans to assess response to therapy. In addition, pharmacokinetic studies on peripheral blood and paired tumor biopsies will be obtained to assess for global demethylation and evaluation of biomarkers. Major eligibility criteria include measureable disease with accessibility for paired tumor biopsies, and prior treatment with irinotecan without limit on number of total therapies. Current Enrollment: Dose level 1 enrolled 6 patients and encountered 1 DLT following expansion for safety assessment. Dose level -1 enrolled 3 patients and encountered 2 DLTs, which has since prompted amendments for additional dose levels with modifications to scheduled growth factor support. Dose level -1G enrollment began in September 2014. Clinical trial information: NCT01896856.