bluuebunny/crossref_metadata_2025_split huggingface dataset:
SWOG S1505: A randomized phase II study of perioperative mFOLFIRINOX versus gemcitabine/nab-paclitaxel as therapy for resectable pancreatic adenocarcinoma.
Authors: Sohal Davendra , McDonough Shannon L , Ahmad Syed A. , Gandhi Namita , Beg Muhammad Shaalan , Wang-Gillam Andrea , Guthrie Katherine A , Lowy Andrew M. , Philip Philip Agop , Hochster Howard S. 
Published: January 2019

TPS547 Background: Clinical outcomes after curative therapy for resectable pancreatic ductal adenocarcinoma (PDA) remain suboptimal. Series show that 70-85% of patients die of systemic recurrence. Improved overall survival (OS) in the metastatic setting with the use of multi-agent chemotherapy regimens (FOLFIRINOX, gemcitabine/nab-paclitaxel) holds the promise of progress in the curative setting as well. However, aggressive systemic therapy is usually not feasible after major pancreatic surgery. Therefore, early control of systemic disease by increased preoperative chemotherapy may improve outcomes. Furthermore, the perioperative platform facilitates early identification of patients with chemotherapy-resistant tumors and allows prospective biomarker studies in the future. Methods: This is a randomized phase II study intended to choose the most promising perioperative regimen to test in a larger trial. Eligibility requirements include adult patients with an ECOG PS of 0 or 1, a confirmed histopathologic diagnosis of PDA, and resectable disease as confirmed by central radiology review: no involvement of the celiac, common hepatic, or superior mesenteric arteries (and, if present, variants); no involvement, or < 180° interface between tumor and vessel wall, of the portal or superior mesenteric veins; patent portal vein/splenic vein confluence; no metastases. Treatment includes 12 weeks [either 6 doses of mFOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin – without bolus 5-FU and leucovorin), or 9 doses of gemcitabine/nab-paclitaxel, on standard schedules] of preoperative chemotherapy, followed by surgical resection and 12 weeks of identical postoperative chemotherapy. Primary outcome is 2-year OS, using a “pick the winner” design with minimum two-year OS of 40% assuming a 58% alternative hypothesis, 88% power, and a 1-sided α of 0.05, providing 90% probability of selecting the better regimen with a total sample size of 150 patients. Correlative studies are planned. The study opened through the National Clinical Trials Network (NCT02562716), and is supported by NIH/NCI/NCTN grants CA180888, CA180819, CA180821, CA180833. Clinical trial information: NCT02562716.
AGITG nabnec: A randomised phase II study of nab-paclitaxel in combination with carboplatin as first line treatment of gastrointestinal neuroendocrine carcinomas.
Authors: Chantrill Lorraine A. , Lipton Lara Rachel , Hofman Michael , Gebski Val , Gill Anthony , Markman Ben , Yip Sonia , Karapetis Christos Stelios , Pavlakis Nick , Wong Shu Fen , Ransom David Turner , Sjoquist Katrin Marie , Nagrial Adnan , Michael Michael , Rayani Uzma , Oostendorp Martinus , Simes John , Khasraw Mustafa 
Published: January 2019

TPS548 Background: Neuroendocrine carcinomas (NEC WHO grade 3) are rare and aggressive cancers. There are no randomised trials to date to establish standard therapy for advanced gastrointestinal (GI) NECs. Extrapolating from small cell lung cancer data, standard practice is to treat GI-NECs with etoposide and carboplatin. Paclitaxel is also active in NECs however there is no data on the role of nab-paclitaxel. NABNEC aims to establish if the carboplatin and nab-paclitaxel combination is an effective and tolerable treatment for advanced GI-NECs and to enhance our understanding of the biology and imaging characteristics of NECs. Methods: Design: Randomised, non-comparative, stratified, multicentre phase 2 trial. Primary endpoint (n=70): objective response rate (RR) by RECIST 1.1 at 6 months. Secondary endpoints: progression free survival, overall survival, adverse events by NCI-CTCAE V4.03 and quality of life (EORTC QLQC30, QLQ-GINET21 questionnaires). Translational endpoints include 1) blood and tissue biomarkers (prognostic and/or predictive) correlated with clinical endpoints including circulating tumour cells, mutation profile (whole exome sequencing), DNA methylation profile; 2) correlation of 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) to early response and other clinical endpoints. Sample Size: 70 patient’s gives 80% power and 95% confidence to rule out a 30% RR in favour of a clinically relevant RR of 50% at 6 months. Population: Adults with advanced or metastatic non-resectable GI-NEC (includes small cell and large cell NEC). Treatment: Randomisation 2:1 to Arm A IV nab-paclitaxel 100 mg/m2 on Day (D) 1 weekly and IV carboplatin AUC=5 on D1, 3 weekly; and Arm B IV etoposide 100mg/m2 on D1-3, and IV carboplatin AUC=5 on D1, 3 weekly to continue until disease progression or unacceptable toxicity. Assessments: 68Ga Octreotate PET at baseline, CT scan at baseline and every 9 weeks, FDG PET at baseline, 9 weeks then every 18 weeks and QOL questionnaires every 9 weeks until disease progression. NABNEC is enrolling patients at 12/20 planned study sites in Australia and New Zealand. ANZCTR #. Clinical trial information: 12616000958482.
Safety of trifluridine/tipiracil (TAS-102) in combination with temozolomide for metastatic neuroendocrine tumors.
Authors: Uboha Nataliya Volodymyrivna , Deming Dustin A. , Lubner Sam Joseph , Mulkerin Daniel , Eickhoff Jens C. , LoConte Noelle K. 
Published: January 2019

TPS549 Background: Low and intermediate grade neuroendocrine tumors (NETs) are incurable once they metastasize. Cytoreductive surgery and locoregional therapies play an important role in their management, but ultimately most patients are treated with systemic therapies. In clinical studies, combination of temozolomide (TMZ) and capecitabine (CAP) demonstrated significant response rates (> 50%) in patients with advanced pancreatic NETs. Trifluridine/tipiracil (FTD/TPI), also known as TAS-102, is a new anti-metabolite agent that is non-cross resistant with 5-fluorouracil (5-FU) and CAP and that has a different toxicity profile from CAP. In clinical trials, FTD/TPI has been associated with limited toxicities in patients with chemotherapy refractory (including 5-FU and CAP) metastatic colorectal cancer. Given that CAP has demonstrated activity in metastatic NETs, we hypothesize that FTD/TPI in combination with TMZ will be well tolerated and will be efficacious in metastatic NETs. Methods: This is a two-part investigator-initiated phase IB clinical trial (NCT02943733). Part 1 is a dose escalation portion of the study that will determine maximum tolerated doses of FTD/TPI administered in combination with TMZ in patients with advanced NETs. Patients with low and intermediate grade NETs of any origin are eligible for part 1. This part follows a classical “3+3” design to establish the phase 2 doses. Both drugs are oral agents that are administered on a 28 day cycle. FTD/TPI is taken twice a day on days 1-5 and days 8-12. TMZ is taken daily on days 8-12. This schedule was selected based on the pre-clinical data demonstrating schedule-dependent synergism between 5-FU and TMZ. Because of concern for overlapping bone marrow toxicities between the two agents, TMZ is started at the dose of 100 mg/m2 and escalated to a goal dose of 200mg/m2 daily if no dose limiting toxicities are observed. FTD/TPI is started at a goal dose of 35 mg/m2. Part 2 of the study will enroll estimated 15 patients with metastatic pancreatic NETs. Primary endpoint of part 2 is overall response rate, and secondary endpoints are progression free survival, disease control rate and overall survival. Part 1 of the trial is currently open to enrollment. Clinical trial information: NCT02943733.
Adjuvant FOLFOX-Nab-paclitaxel (FOLFOX-A) for pancreatic cancer: A phase II Brown University Oncology Research Group (BrUOG) trial.
Authors: Safran Howard , Charpentier Kevin , Mantripragada Kalyan C. , Breakstone Rimini , Miner Thomas J. , DiPetrillo Thomas A. , Marks Eric I , Rosati Kayla , Mitchell Kristen , Rossiter Rachael , Luppe Denise , Rago Molly , Schumacher Andrew , Cavanagh Lindsey 
Published: January 2019

TPS550 Background: The FOLFOX-A regimen was developed by BrUOG, in response to the activity of nab-paclitaxel (nP) in metastatic pancreatic cancer (mPC), by substituting nP for irinotecan in FOLFIRINOX. In a phase I/II study of FOLFOX-A in mPC, median overall survival (OS) was 15 months (Safran H, et al. Am J Clin Oncol, 2016 Dec;39(6):619-622), which motivated evaluation of the tolerability and efficacy of this aggressive regimen in the adjuvant setting. Therefore, a phase II study of FOLFOX-A was initiated for patients with resected pancreatic cancer. Methods: Eligibility criteria included potentially curative resection of pancreatic adenocarcinoma (positive margins allowed if all gross tumor was removed), pathologic stages T1-3/N0-1/M0, interval between surgery and registration of 21-70 days and post resection serum CA19-9 ≤ 180 units/mL. All patients received nab-paclitaxel 150mg/m2, oxaliplatin 85mg/m2 and leucovorin 400mg/m2, followed by fluorouracil 2400mg/m2 infused over 46 hours. Cycles were repeated every 2 weeks. The primary objective is to assess the feasibility of administering at least 10 of 12 planned cycles of FOLFOX-A without unacceptable toxicity in 25 patients. Secondary endpoints include progression-free survival and OS. Results: Between June 2014-August 2017, 19 patients have been enrolled, 8 male and 11 female. Median age is 63 (43-68). Fifteen patients had positive lymph nodes on pathology with stages T1N0(n = 2), T3N0(n = 2), T1N1(n = 1), T3N1(n = 14) [AJCC Cancer Staging Manual, 7th Edition (2010)]. Conclusions: This study is testing the tolerability of administering adjuvant FOLFOX-A to patients with resected pancreatic cancer. Accrual is expected to be complete by January 2018. Clinical trial information: NCT02022033.
Prospective multicenter study of the impact of the 12-gene assay recurrence score on adjuvant chemotherapy treatment recommendations for stage II/III colon cancer in the post-IDEA era: SUNRISE-Decision Impact study.
Authors: Yamanaka Takeharu , Sato Takeo , Nakashima Sayoko , Yoshino Takayuki 
Published: January 2019

TPS868 Background: The results of IDEA collaboration study in ASCO 2017 suggested that adjusting the duration of adjuvant chemotherapy (CTx) for stage III colon cancer may be possible according to patient’s risk (T and N factors) and treatment regimen (FOLFOX and CAPOX) in order to balance the benefit and neurotoxicity of oxaliplatin-based CTx. The 12-Gene Assay Recurrence Score (12-gene RS), known as Oncotype DX, has been validated to predict the recurrence risk of stage II/III colon cancer patients through several studies, including our SUNRISE study (J Clin Oncol, 2016), and thus to personalize adjuvant CTx taking account of individual recurrence risk. The objective of this SUNRISE-DI study is to determine the impact of the 12-gene RS on adjuvant CTx treatment recommendations, including the decision for the duration of oxaliplatin-based CTx in stage III patients as well as that for oxaliplatin-based CTx versus 5FU-based monotherapy in stage II/III patients. This study enables us to evaluate how physicians employ the IDEA collaboration results combined with the 12-gene RS to determine the regimen. Methods: Patients who have a curatively resected Stage II/IIIA/IIIB colon cancer, an age of more than 20, and an ECOG PS of 0-1 are eligible. Treating physicians will formulate a treatment recommendation and complete a pre-assay questionnaire, and the 12-gene assay will be performed. Following receipt of the RS result, the treatment recommendation will be revised and a post-assay questionnaire completed. The primary endpoint is the proportion of changes in treatment recommendations between pre- and post-assay across all patients. Secondary endpoints include the proportion of changes by stage; the proportion of changes in the duration of oxaliplatin-based CTx (3 months vs 6 months); the proportion switched to observation only, 5-FU mono, or 5-FU plus oxaliplatin; and changes in expressed physician confidence level. The enrollment target is 200 patients with stage IIIA/IIIB and 100 patients with stage II from 15 centers in Japan. Clinical trial registry number: UMIN000028784
Phase I/IIb trial: In-situ vaccine for metastatic colorectal cancer.
Authors: Kundranda Madappa N. , Dragovich Tomislav , Price Andrew , Lanauze Philippe , Bloch Miriam , Bishop Michael , Chang John , Har-Noy Michael 
Published: January 2019

TPS871 Background: Except for MSI-H tumors, CRC does not respond to immunotherapy. CRC does respond to the graft vs. tumor (GVT) immune effect that occurs after allogeneic stem cell transplantation. GVT is associated with GVHD toxicity which limits the clinical application. A bioengineered allograft (BAG) has been developed which can elicit host-mediated GVT-like effects without GVHD toxicity, chemotherapy conditioning or a HLA-matched donor. BAG are Th1 memory cells derived from blood of healthy donors with CD3/CD28 microbeads attached. These cells have immunomodulatory properties which enable modulation of Th1/Th2 balance and dysregulation of immunosuppressive circuits. We are evaluating the safety and efficacy of BAG in third-line mCRC. Methods: The study uses a standard 3+3 design followed by an expansion phase with the optimal dosing pattern. The protocol has four components: (A) priming; (B) in-situ vaccination; (C) extravasation and trafficking; and (D) counter immune suppression/avoidance. Priming involves intradermal injections of BAG cells which activates NK cells and develops allo-specific Th1/Tc1 immunity. In-Situ vaccination involves tumor cryoablation to release endogenous HSP which chaperone tumor neoantigens, followed immediately by the intralesional injection of BAG cells as adjuvant. Released HSP are engulfed and processed by immature dendritic cells (DC) attracted to the tissue damage. The inflammatory microenvironment created by the BAG and the subsequent allo-rejection response amplified by the priming induces DC maturation. These DC display processed tumor antigens on upregulated MHCI/II and express co-stimulatory CD80/86 enabling priming of a tumor-specific Th1/Tc1 response. CD40L and interferon-gamma expressed by BAG activates allo-specific and tumor-specific memory cells upon intravenous infusion, permitting trafficking to tumor. The host rejection of BAG releases endogenous danger signals creating a sustained systemic inflammatory cytokine release which serves to counter-regulate immunosuppressive mechanisms. Longitudinal CT scans biopsies, PBMC and serum samples are collected for analysis to verify immune events within each phase of the protocol. Clinical trial information: NCT02380443.
PIER trial: Neoadjuvant therapy with panitumumab (P) and mFOLFOX-6 in an enriched population of patients with T3 rectal adenocarcinoma of the middle third with clear mesorectal fascia.
Authors: Fernandez-Martos Carlos , Aparicio Jorge , Ayuso Juan , Capdevila Jaume , Gallego Javier , Losa Ferran , Maas Monique , Maurel Joan , Pericay Carles , Rodriguez Salas Nuria , Safont Maria Jose , Tobeña Maria , Valladares Manuel , Vera Ruth 
Published: January 2019

TPS875 Background: Retrospective data suggest that patients with advanced colorectal carcinoma wild-type (WT) for RAS, BRAF or Pi3K achieve increased response rates from anti-EGFR therapy as compared with mutated tumors. Neoadjuvant chemotherapy with oxaliplatin/fluoropyrimidine combination has shown to induce encouraging pathological complete response (pCR) in clinically staged T3 rectal cancer tumours (Schragg et al, JCO 2014 and Fernandez-Martos et al, The Oncologist 2014). We hypothesize this efficacy could be improved in a selected population (quadruple WT [4WT]) combining chemotherapy and anti-EGFR therapy. The objective is to assess the feasibility, efficacy and safety of neoadjuvant therapy with mFOLFOX-6 + P in rectal adenocarcinoma patients of intermediate risk and 4WT. Methods: PIER is a prospective, phase II, single-arm, multicentre, open-label clinical trial (NCT03000374). Key eligibility criteria include patients < 75 years with rectal adenocarcinoma in the middle third , clear mesorectal fascia, candidate for R0 resection with sphincter preservation surgery and absence of mutations in KRAS (exon 2 [codons 12/13], exon 3 [codons 59/61] and exon 4 [codon 117/146]), NRAS ( exon 2 [codons 12/13], exon 3 [codons 59/61] and exon 4 [codons 117/146]), BRAF (exon 15 [codon 600]) and PI3KCA in exons 9 and 20. All pre- and post-treatment MRI scans are centrally reviewed. Treatment: 6 induction cycles of mFOLFOX6 + P every 14 days. After the last cycle, a CT-scan, MRI and rectal endoscopy will be performed and patients will undergo TME surgery within 4 weeks +/- 1 week after the last dose. In case of progression patients will receive standard preoperative chemoradiation. The primary end point is pCR; key secondary end points include R0 resection rate, and clinical complete response. Statistical design: 42 evaluable patients (assuming a P0 of 16% and a P1 35%, with 0.1 alfa and 0.1 beta); 2-stage Simon’s optimal design. Enrolment in PIER is ongoing. Clinical trial information: NCT03000374.
INNOVA: A phase II randomized study comparing INterval versus NeOadjuVAnt chemotherapy in magnetic resonance imaging-defined high risk rectal cancer.
Authors: Seshadri Ramakrishnan Ayloor , Ganesan Trivadi S. , M N Arunkumar , Sundersingh Shirley 
Published: January 2019

TPS879 Background: Patients with rectal cancers treated with neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy are not exposed to systemic doses of chemotherapy until very late in the treatment schedule. Preoperative chemotherapy, either in the neoadjuvant or interval setting can lead to early treatment of micrometastasis, improve the tumor response and possibly the overall survival. Phase II studies of neoadjuvant chemotherapy in rectal cancer have shown good response to chemotherapy with no tumor progression and good compliance. A phase II study evaluating the effect of giving chemotherapy in the interval waiting period between chemoradiation and surgery has shown acceptable toxicity and high pathological complete response rates. Methods: This single centre, randomized, open label, phase II trial compares the safety and efficacy of two pre-operative regimens in locally advanced MRI defined high-risk rectal cancers. Based on the Simon optimal two-stage design, 94 patients will be randomised to either Arm A [3 cycles of neoadjuvant chemotherapy (capecitabine and oxaliplatin) followed by chemoradiation (50.4 Gy with capecitabine) and then surgery] or Arm B [neoadjuvant chemoradiation followed by 3 cycles of interval chemotherapy and then surgery]. Patients in both arms receive 3 cycles of adjuvant chemotherapy. The primary end-point is the pathological complete response rate. Secondary end-points include frequency and severity of adverse events, RO resection rates, tumor regression grading and compliance to treatment. The inclusion criteria: age 18 to 70 years; ECOG performance status 0-2; non-metastatic, locally advanced rectal cancer with any one of the following features on high-resolution thin slice MRI: any T3/T4 tumor in the lower rectum, T3c/T3d/T4 tumor in the mid rectum, N2 disease, threatened mesorectal fascia, or extramural vascular invasion. Patients are randomly assigned to one of the two intervention arms in a 1:1 ratio. Prespecified activity goal for the first stage of accrual was met; second stage accrual began in July 2017. Clinical trial information: CTRI/2015/01/005385.
Toca 511 and Toca FC in patients with gastrointestinal tumors in the Toca 6 study.
Authors: Merchan Jaime R. , Ostertag Derek , Jolly Douglas J. , Tejera Dalissa , Gruber Harry E. , Shorr Jolene 
Published: January 2019

TPS880 Background: Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector (RRV). RRVs selectively infect cancer cells due to defects in innate and adaptive immune responses found in cancers that support virus replication, and the requirement for cell division for virus integration into the genome. Toca 511 spreads through tumors, stably delivering an optimized cytosine deaminase (CD) gene that converts the prodrug, Toca FC (investigational, extended-release 5-FC) into 5-FU. 5-FU kills infected dividing cancer cells and diffuses and kills surrounding cancer cells, myeloid derived suppressor cells, and tumor associated macrophages, thus reestablishing tumor immunity (Cloughesy et al. Neuro Oncol 2016). In a Phase 1 study, resected high grade glioma tumors expressed CD protein following intravenous (IV) Toca 511.1 In animal models of metastatic colorectal cancer, IV Toca 511 infected metastatic sites, and subsequent 5-FC treatment resulted in decreased tumor size and improved survival (Yagiz et al. Mol Therapy 2015). Methods: Toca 6 is a Phase 1b, multicenter, open-label study (NCT02576665) that aims to investigate changes in immune activity after treatment with Toca 511 & Toca FC in patients with solid tumors, including gastrointestinal tumors. A total of 30 patients who have advanced malignancies, including colorectal and pancreatic cancer, with molecular characteristics that may increase sensitivity to 5-FU or viral infection, or IDH1 mutated solid tumors (e.g., intrahepatic cholangiocarcinoma) will be enrolled. In these patients, Toca 511 is injected IV daily for 3 days, then intratumorally after biopsy. Oral Toca FC is started ~4 weeks later and repeated every 4-6 weeks. Changes from baseline in intratumoral immune activity (infiltrating T-cell subpopulations, B cells, monocytes) at 4 weeks after start of Toca FC are assessed. Contemporaneous peripheral blood is analyzed for effector, memory, Treg, and myeloid lineage cells. Viral RNA, DNA, and CD protein expression in tumor after IV Toca 511 are measured. Safety and efficacy will be determined. Concomitant checkpoint inhibitor therapy may be given following immune activity assessments. The study has enrolled 3 patients. Clinical trial information: NCT02576665.