bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I multicenter study of the combination of temozolomide and pazopanib in advanced pancreatic neuroendocrine tumors (PNET).
Authors: Kalyan Aparna , Kircher Sheetal , Denlinger Crystal Shereen , Berlin Jordan , Mulcahy Mary F , Cohen Steven J. , Chiorean E. Gabriela , Zalupski Mark , Benson Al Bowen , Nimeiri Halla Sayed 
Published: February 2017

TPS492 Background: Everolimus and sunitinib targeted therapy have proven efficacy in advanced PNET, with ORR 5-9% and PFS HR < 0.5 compared to placebo.Additionally, a single arm phase II study showed promising activity with temozolomide and capecitabine combination with an ORR of 70%. Rationale:PNETs are distinguished by their vascularlity and up-regulation of VEGF factors. In the preclinical setting, the combination of temozolomide and sunitinib appears to act synergistically by altering the tumor microenvironment enhancing activity of temozolomide. Pazopanib has shown activity in a single arm phase II study in advanced PNETs with a 6-month PFS rate of 80% and ORR of 17%. There is sufficient preclinical and clinical evidence suggesting that the combination of an anti-angiogenic agent with temozolomide is more efficacious, hence, our rationale for the current study. Methods: Objectives: (1) Determine the MTD and toxicity profile of temozolomide + pazopanib. (2) Describe the PK profile of this combination. (3) Observe the ORR. Trial Design:Open label Phase I study to determine the MTD and safety profile employing a 3+3 dose-escalation model of the combination of temozolomide and pazopanib in patients with advanced PNET who have received between 1-4 prior therapies. Cohort 1: temozolomide at 150 mg/m2 on Days 1-7 and 15-21, and pazopanib 400 mg orally once daily continuously throughout cycle of 28 days. Once MTD is determined, PK sampling will be performed in 6 additional patients enrolled at the MTD. To date, eleven patients have been enrolled in cohort 1 and cohort -1. Cohort -1 is currently accruing at the reduced dose level of temozolomide 100mg/m2 and pazopanib 400mg daily for the duration of the cycle. The trial is funded to proceed to a single arm phase II with exploratory end points: (1) Correlation of MGMT expression by IHC to ORR and PFS (2) tumor blood flow (perfusion CT imaging) relationship with ORR. (This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by GlaxoSmithKline.) Clinical Trial information: NCT01465659. Clinical trial information: NCT01465659.
Phase Ib study of PGG beta glucan in combination with anti-MUC1 antibody (BTH1704) and gemcitabine for the treatment of advanced pancreatic cancer.
Authors: Venepalli Neeta K. , Gandhi Chintan Chandrakant , Ozer Howard , Ho Dominic , Lu Yang , Xie Hui , Berg Stephanie A. , Chowdhery Rozina A. , Gargano Michele Anne , Braun Ada H. , Dudek Arkadiusz Z. 
Published: February 2017

TPS493 Background: Mucin 1 (MUC1) is a tumor associated membrane-bound glycoprotein that promotes oncogenesis through promotion of epithelial cell polarity loss, anti-apoptosis, and hypoxia driven angiogenesis. MUC1 overexpression is associated with aggressive behavior and poor outcomes in pancreatic ductal adenocarcinoma (PDAC), and increased resistance to gemcitabine (G) in vitro. BTH1704 (BTH) is a humanized monoclonal antibody (MAb) targeting aberrantly glycosylated MUC1. Imprime PGG (PGG) is a soluble yeast-derived b 1,3/1,6 glucan that binds complement receptor 3 (CR3) on innate immune cells priming them to exert anti-tumor activity against complement (iC3b) opsonized tumor cells. Following incubation of PGG with whole blood from healthy subjects, variability in PGG binding to neutrophils and monocytes has been observed, with higher binding and functional changes correlating with higher levels of endogenous anti-b glucan antibodies. BTH binds to antigens (MUC1), leading to iC3b opsonization of tumor cells thus, allowing PGG-primed leukocytes to kill the iC3b-opsonized tumor cells. This forms the rationale for testing BTH1704 combined with G + PGG. Methods: This is a single institution Phase 1b dose escalation study with a standard 3x3 design to determine the maximal administered dose (MAD) of BTH combined with G + PGG in patients with previously treated advanced PDAC.Each dose cohort includes at least one subject with high and one low PGG binding capability. Primary objectives: establish MAD of BTH combined with G + PGG. Secondary objectives: characterize adverse effects, clinical response, time to progression, progression free and overall survival. Correlative objectives: quantify PGG binding, MDSC phenotyping of PBMC, anti b glucan antibody levels, MUC1 IHC. Inclusion criteria: confirmed advanced PDAC, ECOG PS 0-2, rest period 2-6 weeks from prior first- or second-line treatment. Exclusion criteria: uncontrolled chronic illness. Administration and design: BTH and PGG are administered on days 1, 8, 15, and 22 of a 28-day cycle; G is administered on days 1, 8, and 15. The study is currently enrolling patients. Clinical trial information: NCT02132403. Clinical trial information: NCT02132403.
Neonax (AIO-PAK-0313): Neoadjuvant plus adjuvant or only adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer: A phase II study of the AIO Pancreatic Cancer Group.
Authors: Ettrich Thomas Jens , Berger Andreas W. , Muche Rainer , Lutz Manfred P. , Prasnikar Nicole , Uhl Waldemar , Tannapfel Andrea , Heinemann Volker , Seufferlein Thomas 
Published: February 2017

TPS497 Background: Resectable pancreatic cancer still has an unfavourable prognosis. Neoadjuvant or perioperative therapies might improve the prognosis of these patients. Recently, two phase III trials demonstrated for the first time, a substantial improvement in overall response, PFS and OS in patients with metastatic pancreatic cancer compared to standard gemcitabine (FOLFIRINOX and nab-paclitaxel/gemcitabine). The combination of nab-paclitaxel/gemcitabine has a more favourable toxicity profile compared to the FOLFIRINOX protocol and appears applicable in a perioperative setting. Methods: NEONAX is a study for patients (to be enrolled: n=166) with resectable ductal adenocarcinoma of the pancreas ≤ T3 in two arms: Arm A (perioperative arm): 2 cycles nab-paclitaxel (125 mg/m2)/gemcitabine (1000 mg/m2, d1, 8 and 15 of an 28 day-cycle) - tumor surgery - 4 cycles nab-paclitaxel/gemcitabine, Arm B (adjuvant only arm): tumor surgery - 6 cycles nab-paclitaxel/gemcitabine. NEONAX is an interventional, prospective, randomized, controlled, open label, two sided phase II study with an unconnected analysis of the results in both experimental arms against a fixed survival probability (38% at 18 month with adjuvant gemcitabine). The randomization (1:1) is eminent to achieve two comparable patient groups. Primary objective is DFS at 18 months after randomization. Key secondary objectives are 3-year OS and DFS, progression during neoadjuvant therapy and QoL. In the perioperative group tumor tissue will be collected prior to and post-surgery and subjected to microdissection and exome sequencing of tumor tissue. Tumor regression will be assessed both in the perioperative and the adjuvant group, respectively. In addition, circulating tumor-DNA will be analyzed in patients with the best and the worst responses to the neoadjuvant treatment. Start of trial will be in IV/2014 in 20 high-volume centers for pancreatic surgery in Germany. Clinical trial information: NCT02047513. Clinical trial information: NCT02047513.
A multicenter randomized phase II study of NPC-1C (N) in combination with gemcitabine (G) and nab-paclitaxel (A) versus G and A alone in patients with metastatic or locally advanced pancreatic cancer (PC) previously treated with folfirinox (F).
Authors: Duffy Austin G. , Beg Muhammad Shaalan , Greten Tim F. , Beatson Melony A. , Mavroukakis Sharon , Patel Sandip Pravin , Morse Michael A. , Arlen Philip M. 
Published: February 2017

TPS499 Background: PC carries a poor prognosis. F has improved overall survival (OS) compared to G leading to its use as a 1st line treatment for patients (pts) with advanced PC. Similarly, the combination of G and A has demonstrated OS benefit. No data exists for G/A in the 2nd line setting. Many oncologists continue to sequence F treatment followed upon disease progression by G/A for pts with advanced PC with good performance status. N is a chimeric monoclonal IgG1 antibody recognizing an aberrantly glycosylated MUC5AC specific to GI tumors. Its mechanism of action is through ADCC. An IHC based companion diagnostic assay is utilized to select pts whose tumors express the target (approx. 65-70%). A prior study administering N to pts with advanced PC refractory to chemotherapy was well tolerated with disease stabilization and prolongation of OS. Furthermore 2 of 5 pts receiving the combination of G+N following progression on F remain alive at 10 and 12 months respectively. Methods: The primary objective of this phase 2.5 study is to determine if the combination of N and G plus A can improve the OS for pts who have PC over G plus A alone in the post F setting. The trial is a 2-arm randomized 1:1 multi-institution trial of N plus G and A vs. G and A. Eligible pts would be expected to have an estimated 4.5 to 4.8 month median OS with G alone, but this may be enhanced somewhat with the addition of A. The goal is to determine if the use of N along with G and A will result in pts having an increased median OS of 8 months vs. an estimated 5 months without N. Kaplan-Meier curves and a two-tailed log-rank test will be the primary analysis methods. All pts must have tissue positive for the MUC5AC variant (≥20% by IHC). Because N has been established to be safe when given with G alone but not with the combination of G and A, stopping rules for safety will be adhered to for the first 6 pts randomized to G/A plus N. Enrollment to the study has commenced. Correlative studies will utilize both PBMCs and serum for immune monitoring. Frequency, phenotype and function of different immune cells (including CD8+ T cells, CD4+ T cells, Tregs and MDSCs) will be analyzed. Clinical trial information: NCT01834235.
S1406: Randomized phase II study of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (mCRC).
Authors: Kopetz Scott , McDonough Shannon , Morris Van Karlyle , Lenz Heinz-Josef , Magliocco Anthony M. , Atreya Chloe Evelyn , Diaz Luis A. , Allegra Carmen Joseph , Lieu Christopher Hanyoung , Eckhardt S. Gail , Semrad Thomas John , Kaberle Kimberly , Guthrie Katherine , Hochster Howard S. 
Published: February 2017

TPS790 Background: BRAFV600 mutations are associated with inferior survival and objective responses to the mutated BRAF inhibitor vemurafenib in patients with mCRC. Blockade of BRAFV600 by vemurafenib causes feedback upregulation of EGFR, whose signaling activities can be impeded by cetuximab. In murine models of BRAFV600 mCRC, the addition of irinotecan to vemurafenib and cetuximab leads to greater anti-tumor activity. Recent phase I studies with the combination of BRAF and EGFR inhibition resulted in response rates substantially higher than either agent alone, with objective responses in 4 of 8 BRAFV600 mCRC patients treated with vemurafenib, cetuximab, and irinotecan. Methods: The SWOG 1406 trial (NCT 02164916) is a randomized phase II study of irinotecan (180 mg/m2 IV every 14 days) and cetuximab (500 mg/m2 IV every 14 days) with or without vemurafenib (960 mg PO twice daily). Eligible adult patients have histologically confirmed colorectal adenocarcinoma with metastatic disease. Tumors must have a BRAFV600 mutation and be wild-type for KRAS and NRAS. BRAF testing may be conducted using any CLIA-compliant lab. Alternatively, screening can be provided through a central lab. Patients must have received one or two prior systemic regimens for unresectable locally advanced or metastatic disease and must not have received anti-EGFR agents. Prior treatment with irinotecan is allowed. Patients randomized to the control arm may crossover to the experimental arm at progression. Target enrollment is 78 patients. The primary endpoint is PFS. Optional participation in a co-clinical trial will be offered in selected sites whereby patients’ biopsies will be used to establish patient-derived xenografts to study correlations between patient and PDX with respect to treatment responses and mechanisms of treatment resistance. This trial has support from all adult cooperative groups and utilizes the Central IRB to facilitate study initiation. Conclusions: mCRC patients harboring BRAFV600E mutations may benefit from EGFR and BRAF blockade. We encourage screening for the BRAF mutation early in the course of metastatic disease therapy and for second line therapy on this trial. Clinical trial information: NCT 02164916.
InterAACT: An international multicenter open label randomized phase II advanced anal cancer trial comparing cisplatin (CDDP) plus 5-fluorouracil (5-FU) versus carboplatin (CBDCA) plus weekly paclitaxel (PTX) in patients with inoperable locally recurrent (ILR) or metastatic disease.
Authors: Sclafani Francesco , Adams Richard A. , Eng Cathy , Benson Al Bowen , Glynne-Jones Robert , Sebag-Montefiore David , Arnold Dirk , Roy Amitesh Chandra , Guren Marianne Grønlie , Segelov Eva , Seymour Matthew T. , Bryant Annette , Peckitt Clare , Cunningham David , Bridgewater John A. , Welch Jack , O'Dwyer Peter J. , Dupont Elisabeth , McConnell Andrea , Rao Sheela 
Published: February 2017

TPS792 Background: Metastatic squamous cell carcinoma of the anus (SCCA) is a rare condition with 5-year overall survival (OS) rate of 32%. CDDP/5-FU is commonly used in the first-line treatment of patients with ILR or metastatic disease. This practice is based on retrospective series and data from randomised trials are lacking. Recent retrospective studies showed promising activity of CBDCA/PTX in this setting. Methods: InterAACT is an international, multicentre, open label, randomised phase II trial comparing two chemotherapy regimens in patients with ILR or metastatic SCCA. Eligible patients are randomised in a 1:1 ratio to CDDP (60 mg/mq, D1q21) plus 5-FU (1000 mg/mq/24h, D1-4q21) or CBDCA (AUC 5, D1q28) plus PTX (80 mg/mq, D1,8,15q28). Stratification factors are: performance status, extent of disease, HIV status and country. The primary endpoint is response rate (RR). Secondary endpoints include progression-free survival, OS, toxicity and quality of life. Based on a RR estimate of 40% in the CDDP/5-FU arm 80 patients are to be recruited to detect 10% difference in RR between the two arms with 80% power (phase II selection trial design). Correlative biomarker analyses are planned in tumour tissue and blood samples. The trial is sponsored by The Royal Marsden NHS Foundation Trust and endorsed by the International Rare Cancer Initiative (IRCI) group. Approximately 50 centres in the UK, Europe (EORTC), Scandinavia, US (ECOG-ACRIN) and Australia (AGITG) are estimated to participate and recruitment is anticipated to be completed within 3 years. Recruitment started in December 2013. As of September 16, 2014, 6 sites in the UK are open to recruitment and 6 patients have been randomised (3 to CDDP/5-FU and 3 to CBDCA/PTX). InterAACT aims to provide the first randomised evidence for the treatment of ILR and metastatic SCCA, to identify the optimal chemotherapy backbone to combine with targeted agents in future studies and to confirm the feasibility of conducting an international multicentre trial for this rare tumour. Clinical trial information: NCT02051868.
Preoperative D-dimer measurement for assessment of venous thromboembolism in colorectal cancer cases.
Authors: Hatta Kazuha , Ogawa Shimpei , Bamba Yoshiko , Hirosawa Tomoichiro , Itabashi Michio , Kameoka Shingo 
Published: February 2017

TPS799 Pre-operative D-dimer Measurement for Assessment of Venous Thromboembolism in Colorectal Cancer Cases Background: In Japan, the incidence of venous thromboembolism (VTE) has recently been increasing and gaining attention. Operation or Malignancy is one of the major factors leading to VTE. Thus, there is an urgent need for appropriate pre-operative risk assessment and thorough preventive measures. Caprini score has proven effective and is widely used, however, since the point system is a little cumbersome, there is a strong demand for a risk assessment system that can be more easily used extensively. Methods: This study involving general surgery cases was performed in our department a period of one-half of a year. In order to screen for pre-operative VTE, D-dimer level was measured in 471 general surgical cases (143 colorectal cancer cases, and 99 the other cancer cases, 229 non-cancer cases), and the cases with high D-dimer levels (>1 μg/mL) underwent venous duplex scanning and enhanced computed tomography. Caprini score was measured in all cases for individual VTE risk assessment. By comparing D-dimer levels and Caprini score, the significance of D-dimer testing for VTE screening and risk assessment was reviewed. Results: D-dimer levels were measured in 471 general surgical cases. The 157 cases with high D-dimer levels (>1 μg/mL) underwent venous duplex scanning and enhanced computed tomography. Pre-operative VTE was detected in 16 cases, and the overall prevalence of VTE was 3.4%. For individual VTE risk assessment, Caprini score was derived for all 471cases. Average Caprini score was 5.54 (±1.78) in the high D-dimer group and 4.67 (±1.76) in the low D-dimer group. Using the t-test, Caprini score increased with increasing D-dimer level (P=<0.001). Focused on 143 colorectal cancer cases, 55 with high D-dimer levels and pre-operative VTE detected in 5 cases (3.5%), and Caprini score was 6.51(±1.46) in the high and 5.91(±1.28) in the low (P=0.0141). Conclusion: This observational study suggested that simple D-dimer testing might be worth discussing and considering not only to screen for pre-operative VTE, but also to assess the perioperative VTE risk levels.
The first results of targeted screening with a distress thermometer and initiation of psycho-oncological care of cancer patients.
Authors: Angerer-Shpilenya Maria , Heidenreich Axel 
Published: February 2017

113 Background: Tumor disease has not only somatic but also psychological impact on patients with complete change of life dimension. This resonates not only to the patients, their relatives and friends, but also to the therapy. A precise screening helps to determine the stress factor, to capture the psychological comorbidity and to initiate an early psycho-social care. Methods: 420 patients with various tumors got since October 2011 in the Urological Clinic of Aachen University Hospital screening using a Distress Thermometer. 410 patients were stationary and 10 patients came to the outpatient (ambulant) chemotherapy. 23 of the 40 questions of the Distress Thermometer depend on somatic complaints of patients. The other 17 questions cover the psycho-social problems. Results: 141 of the 420 patients reported to have a low stress level by the tumor. 139 patients showed, according to the Distress Thermometer, an average and 140 patients significantly higher stress level. This means that 279 of the 420 patients need a psycho-oncological counseling and possibly even further care and treatment. The most common entered symptoms were fears, nervousness, sleep disturbances, fatigue, sadness and worry. Depending on the wishes of the patient the psycho-oncological consultation was initiated. Only completing the Distress Thermometer helps the patient to face their problems and worries and makes perhaps the first great step in the perception of the disease. Since January 2012 a new component was inserted into the discharge reports of the tumor patients. This component contains the recommendation, depending on the result of the Distress Thermometer, to start if necessary the professional psycho-oncological support. That gives the patients a sense of security and a feeling not to fight alone against the disease. Conclusions: A targeted screening and an interdisciplinary, together with psycho-oncologists, care to cancer patients support them and their families at all stages of the disease, helps to deal with the new life situation and can possibly also increase the patient's compliance and the therapeutic response.
Does incidental FDG PET uptake in the prostate have significance?
Authors: Brown Anna Mary , Lindenberg Maria Liza , Sankineni Sandeep , Johnson Linda M , Pruthy Suneha , Merino Maria J , Wood Bradford J. , Pinto Peter A. , Choyke Peter L. , Turkbey Baris 
Published: February 2017

115 Background: 18F-FDG PET/CT is widely used to diagnose malignancy, but is not recommended for localized prostate cancer. This study explores the value of multi-parametric MRI (mpMRI) in characterizing incidentally detected prostate FDG uptake. Methods: Thirty-one patients who underwent FDG PET/CT and prostate MRI were eligible for this study. 14 patients were excluded (n=8 insufficient histopathology, n=6 radical prostatectomy before PET), with final analysis of 17 patients. The mpMRI sequences included T2-weighted, dynamic contrast enhancement (DCE), apparent diffusion coefficient (ADC), and MR spectroscopy (MRS). Nuclear medicine physicians, blinded to clinicopathologic findings, identified suspicious areas and maximum standardized uptake values (SUVmax) on FDG PET/CT. The lesion and sector-based imaging findings were correlated with annotated histopathology from whole-mount or MRI/TRUS fusion biopsy samples. Positive predictive values (PPVs) were estimated using generalized estimating equations with logit link. Results were evaluated with Kruskal-Wallis and Dunn’s multiple comparisons tests. Results: The PPV of FDG PET alone in detecting prostate cancer was 0.56. Combining FDG (base parameter) with mpMRI modalities (T2, DCE, ADC, MRS) increased the sector-based PPV to 0.79, 0.82, 0.80, and 0.89, respectively. All benign lesions had SUVmax < 5, and malignant lesions had higher mean SUVmax values that correlated with Gleason scores [Table]. This relationship between SUVmax and Gleason score was significant, with p=0.012 on the Kruskal-Wallis test and p=0.015 on the Dunn’s multiple comparisons test for Gleason 0 vs Gleason ≥ 4+5. Conclusions: Incidental prostate FDG uptake has low clinical utility alone, but these areas may harbor high-grade prostate cancer, especially if the SUVmax is greater than 5. [Table: see text]