bluuebunny/crossref_metadata_2025_split huggingface dataset:
An investigator sponsored phase Ia/Ib trial of selinexor in combination with irinotecan in patients with adenocarcinoma of stomach and distal esophagus.
Authors: Soares Heloisa P. , Kim Richard D. , Almhanna Khaldoun , Willians-Elson Irene , Kothari Nishi , Mahipal Amit 
Published: February 2017

TPS176 Background: The karyopherin protein Exportin 1 (XPO1) is highly expressed and associated with poor prognosis in gastroesophageal tumors. XPO1 is responsible for nuclear export of major tumor suppressor proteins and other proteins including topoisomerases leading to carcinogenesis and drug resistance. KPT-330 (selinexor) is an oral, first in class, covalent Selective Inhibitor of Nuclear Export that specifically blocks XPO1. In gastric cancer xenograft models, treatment with selinexor resulted in > 75% inhibition of tumor growth. Synergistic activity has been observed with the combination of XPO1 inhibitors and topoisomerase inhibitors. Methods: This is a phase I study with cohort expansion that utilizes the standard 3+3 design for dose escalation. The primary endpoint is to evaluate the safety, tolerability and determine the maximally tolerated dose (MTD) of selinexor in combination with irinotecan. Patients with recurrent, metastatic or unresectable histologically confirmed gastric or distal esophageal adenocarcinomas are eligible for this study. Patients must have received at least one line but less than three lines of prior systemic therapies. Secondary endpoints are to explore the safety, tolerability and efficacy of this combination at the established MTD and characterize its pharmacokinetics. Correlative studies will be performed to assess if differential levels of serum and tissue biomarkers including XPO1, cytokine levels and changes in gene expression, before and after selinexor dosing, correlate with clinical outcomes. Circulating tumor cells will be collected in the expansion cohort. Up to 18 patients will be enrolled in 3 dose level cohorts (40, 50 and 65mg/m2) of selinexor in combination with irinotecan (125mg/m2). Selinexor will be given orally on days 1, 3, 8 and 10 of a 21 days cycle. Irinotecan will be given on days 1 and 8. The MTD is defined as the highest dose level at which 1 or less of 6 patients experience a DLT. An additional cohort of 15 patients will be accrued once the recommended dose for expansion is determined. As per September 2015, 3 patients have been included on cohort 1. Clinical trial information: NCT02283359 Clinical trial information: NCT02283359.
A phase II study of laparoscopic hyperthermic intraperitoneal chemoperfusion (HIPEC) for gastric carcinomatosis or positive cytology.
Authors: Badgwell Brian D. , Blum Mariela A. , Das Prajnan , Elimova Elena , Mansfield Paul F. , Ajani Jaffer A. 
Published: February 2017

TPS186 Background: Over the last 2 decades, intraperitoneal chemotherapy has been found to have activity for select subgroups of patients with carcinomatosis from colon, ovarian, appendiceal, and recently, gastric origins. However, there is little data to support an aggressive surgical approach of cytoreduction (debulking) and HIPEC for patients with gastric cancer and positive cytology or carcinomatosis. The morbidity and mortality rates of cytoreduction and HIPEC, in combination with gastrectomy, are significant and the survival rates of this approach may not extend beyond that of treatment with systemic chemotherapy. The purpose of this clinical trial, therefore, is to perform HIPEC in a neoadjuvant fashion via a minimally invasive approach without cytoreduction for patients with gastric cancer and positive cytology or low volume carcinomatosis. Patients found to have resolution of all extra-gastric disease will then be candidates for gastrectomy. Methods: Patients with gastric and gastroesophageal adenocarcinoma and positive peritoneal cytology or radiologically-occult carcinomatosis that have completed treatment with systemic chemotherapy are offered participation in the study. Type and duration of systemic chemotherapy is left to the discretion of the treating medical oncologist. Laparoscopic HIPEC consists of Mitomycin C 30 mg and Cisplatin 200 mg in 3-7 liters of infusate circulated using an extracorporeal circulation device at a flow rate of 700-1500 mL/minute for 60 minutes, performed no sooner than 3 weeks after completion of systemic chemotherapy. The Laparoscopic HIPEC procedure may be performed up to 5 times, with a minimum of 3 weeks between procedures. After laparoscopic HIPEC, subjects whose disease did not progress will proceed to surgery with diagnostic laparoscopy and possibly exploratory laparotomy to assess resectability, and if their cancer is resectable will undergo gastrectomy. After completion of study–related treatment, subjects will be followed until recurrence and/or death for up to five years. Fourteen of planned 30 patients have been enrolled (NCI-2014-01105). Clinical trial information: NCI-2014-01105.
PLATFORM: Planning treatment of oesophago-gastric (OG) cancer—A randomised maintenance therapy trial.
Authors: Cafferkey Catherine , Chau Ian , Thistlethwaite Fiona , Petty Russell D. , Starling Naureen , Watkins David , Rao Sheela , Saffery Claire , Patel Bijal , Peckitt Clare , Cunningham David 
Published: February 2017

TPS187 Background: Outcomes for patients with advanced OG cancer remain poor, median overall survival for fit patients treated with platinum and fluoropyrimidine based chemotherapy is less than one year, with second line chemotherapy resulting in a modest (approximately 6 weeks) survival benefit for selected patients. Evidence from NSCLC trials suggests a survival benefit from maintenance treatment following first line chemotherapy. Emerging data also supports the use of immunotherapy in previously treated OG cancer. The PLATFORM study aims to evaluate maintenance therapy in patients with advanced OG cancer. Methods: This is a prospective, open label, multicentre, randomised phase II clinical trial which will recruit at multiple UK cancer centres. Eligible patients are those who have measurable stable disease or better following completion of first line chemotherapy (at least 6 cycles) for locally advanced unresectable or metastatic disease. First line chemotherapy regime should contain a platinum and 5-fluoropyridimine (with trastuzumab if HER2 +), doublet or triplet drug combinations are permitted. Maintenance strategies are split by HER 2 status. For HER2 negative patients these are: Arm A1: surveillance, Arm A2: capecitabine, Arm A3: MEDI 4736 (anti PDL1 inhibitor) and for HER2 positive patients; Arm B1: trastuzumab, Arm B2: in development. Target recruitment is six hundred and sixteen patients, 154 patients will be recruited to each arm, with an interim analysis following recruitment of 61 patients to each arm. An adaptive trial design enables ineffective treatments to be discontinued early, with the opportunity to add novel treatment arms as the trial progresses. Primary endpoint is progression free survival. Secondary endpoints are progression free rate at 3, 6 & 12 months, overall survival, objective response rate by RECIST 1.1, toxicity and analysis of efficacy endpoints according to biomarker status for selected arms. Thirty two patients have been registered for the study with 3 patients randomised, recruitment is ongoing. Clinical trial information: EUDRACT: 2014-002169-30.
A phase I study of veliparib (ABT-888) in combination with capecitabine (C) and temozolomide (T) in patients (pts) with advanced well-differentiated unresectable neuroendocrine tumors (wdNET).
Authors: Thota Ramya , Dahlman Kimberly Brown , Koyoma Tatsuki , Berlin Jordan 
Published: February 2017

TPS466 Background: Veliparib (V) is a novel orally bioavailable PARP-1 and -2 inhibitor which potentially synergizes with temozolomide (T). A single arm phase II study combining C and T has shown promising activity in well-differentiated NETs with overall response rate of 43%. Hence, we propose to combine V with C and T optimizing the interaction of V with T by dosing the V during the T to produce improved clinical activity in pts with wdNETs. Methods: This is an investigator initiated, single institution, phase I, dose-escalation trial using a modified Toxicity Probability Interval (mTPI) design. The primary objective is to estimate the maximum tolerable dose (MTD), which is defined as the dose level at which the probability of dose limiting toxicities (DLTs) is 0.33. Secondary objectives include assessing safety profile, antitumor activity and progression free survival. Inclusion criteria: Pathologically confirmed metastatic unresectable well-differentiated (low grade and intermediate grade) NETs that demonstrate progressive disease in the prior 12 months, ECOG PS 0-2 and adequate organ function. Exclusion criteria: severe hypersensitivity reaction to C, 5-FU, T or dacarbazine or uncontrolled chronic illness. Prior treatment with both C and T. Administration and design: We initially will fix doses of C and T at C: 750 mg/m2 po twice a day (BID) on days 1-14 and T at 100 mg/m2 po BID on days 10-14. V is given orally on days 10-14 along with T. We have 5 planned V dose levels (20, 40, 60, 80, 100 mg). If dose level 1 is too toxic we will go to C 600 mg/m2, T 75 mg and V 20 mg. Patients will be enrolled in cohorts of 3. The dose escalation/de-escalation will be as per pre-specified guidelines from the mTPI design. The planned sample size is 21 based on the anticipated number of patients available for this study within 18 months. This trial will be terminated when the maximum sample size (21) is reached or if the lowest dose is deemed too toxic. The study will start enrolling patients October 2015.
APACT: Phase III randomized trial of adjuvant treatment with nab-paclitaxel (nab-P) plus gemcitabine (Gem) versus Gem alone in patients (pts) with resected pancreatic cancer (PC).
Authors: Tempero Margaret A. , Cardin Dana Backlund , Goldstein David , O'Reilly Eileen Mary , Philip Philip Agop , Riess Hanno , Macarulla Teresa , Yung Lotus , Li Mingyu , Lu Brian D. , Biankin Andrew 
Published: February 2017

TPS473 Background: Gem therapy improves outcomes in pts with resected PC. However, disease recurrence is common, prompting a need for improved regimens. nab-P + Gem was superior to Gem alone in MPACT, a phase III trial of pts with metastatic PC (mPC) for all endpoints, including overall survival (OS; median, 8.7 vs 6.6 months; hazard ratio [HR] 0.72; P < 0.001). Toxicities were manageable and consistent with prior studies. The APACT trial will compare adjuvant nab-P + Gem vs Gem alone in pts with resected PC. Methods: Pts (≈ 800) with confirmed PC (R0 or R1 resection); stage T1 - 3, N0 - 1, M0; Eastern Cooperative Oncology Group performance status ≤ 1; adequate organ function; and CA19-9 < 100 U/mL within 14 days of randomization are eligible. Pts with mixed-origin tumors; present or previous mPC; any other malignancy within 5 years of randomization; HIV or hepatitis B or C infection; or prior neoadjuvant treatment or radiotherapy for PC are ineligible. Randomization should occur once pts adequately recover from surgery but ≤ 12 weeks after surgery. Pts will receive 6 cycles of either nab-P 125 mg/m2 plus Gem 1000 mg/m2 or Gem 1000 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Stratification factors are resection (R0 vs R1) and nodal (LN+ vs LN−) status and geographic region (North America vs Europe vs Australia vs Asia Pacific). Pts with > 2 dose reductions will be discontinued. The primary endpoint is independently assessed disease-free survival (DFS). Secondary endpoints are OS and safety. Quality of life and correlation of tumor heterogeneity with clinical outcome are exploratory outcomes. At least 489 DFS events from 800 pts will allow 90% power to detect an HR for DFS of 0.74 at a 2-sided significance level of 0.05. Interim analyses, 1 for safety (after 100 pts are treated for ≥ 2 cycles) and 2 for efficacy (the first for futility and the second for futility and superiority), will be performed. As of July 2015, > 400 pts were enrolled, and 80% of all activated study sites (n = 141) randomized ≥ 1 pt. Of the 674 screened pts, ≈ 25% were ineligible, mainly due to postsurgical disease recurrence identified at screening. Pt enrollment is ongoing. ClinicalTrials.gov: NCT01964430. Clinical trial information: NCT01964430.
A randomized, multicenter, double-blind, placebo-controlled study of the Bruton tyrosine kinase inhibitor, ibrutinib, versus placebo in combination with nab-paclitaxel and gemcitabine in the first-line treatment of patients with metastatic pancreatic adenocarcinoma (RESOLVE).
Authors: Tempero Margaret A. , Coussens Lisa M , Fong Lawrence , Manges Robert , Singh Priyanka , Li Yunfeng , Cole George W. , James Danelle Frances , Tabernero Josep 
Published: February 2017

TPS483 Background: Advanced pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis and short survival. Nab-paclitaxel/gemcitabine (Nab-P/GCB) is a preferred regimen for front-line treatment. The Bruton tyrosine kinase (BTK) inhibitor ibrutinib (ibr) shows antitumor activity in preclinical PDAC models, in part, due to modulation of the tumor microenvironment. Ibr treatment inhibits mast-cell degranulation and decreases tumor-associated inflammation and desmoplasia with simultaneous enhanced presence and activity of cytotoxic T cells in tumors (Affara et al, Cancer Cell, 2014; Masso-Valles et al, Cancer Res, 2015). This randomized trial will evaluate the efficacy of ibr in combination with Nab-P/GCB. Methods: The randomized, multicenter, double-blind RESOLVE trial (NCT02436668; PCYC-1137-CA) will compare ibr vs. placebo in combination with Nab-P/GCB in approximately 320 patients with untreated metastatic PDAC. Key eligibility criteria include histologically confirmed metastatic PDAC; stage IV diagnosis within 6 weeks of randomization; adequate hematologic, hepatic, and renal function; and Karnofsky performance score ≥ 70. Key exclusion criteria include prior therapies (chemotherapy for primary PDAC, BTK inhibitor, or radiotherapy), neuroendocrine or acinar pancreatic carcinoma, known brain or leptomeningeal disease, and history of stroke or intracranial hemorrhage < 6 months prior to enrollment. Patients will be randomized to oral ibr (560 mg) or matched placebo given daily in combination with Nab-P (125 mg/m2) and GCB (1,000 mg/m2) on days 1, 8, and 15 of a 28-day cycle until disease progression or treatment is no longer tolerated. A safety run-in phase will evaluate the ibr combination prior to the randomization portion of the study. The primary endpoint is progression-free survival; secondary endpoints include overall survival and safety. Enrollment in the trial has been initiated. Clinical trial information: NCT02436668.
Ibrutinib + durvalumab (MEDI4736) in patients (pts) with relapsed or refractory (R/R) pancreatic adenocarcinoma (PAC): A phase Ib/II multicenter study.
Authors: Borazanci Erkut Hasan , Hong David S. , Gutierrez Martin , Rasco Drew W. , Reid Tony R. , Veeder Michael H. , Tawashi Ahmed , Lin Jennifer , Dimery Isaiah W. 
Published: February 2017

TPS484 Background: PAC is an aggressive disease characterized by poor prognosis and is inadequately treated with available therapies. Ibrutinib is a first-in-class, oral inhibitor of Bruton’s tyrosine kinase (BTK) that was shown to inhibit mast cell degranulation in the PAC tumor microenvironment with subsequent inhibition of tumor cell proliferation, angiogenesis, and collagen deposition (Chang, 2011; Masso-Valles, 2015). Durvalumab, a human IgG1 monoclonal antibody (mAb), binds PD-L1 with high affinity and prevents interaction with PD-1 and CD80 (IC50values of 0.1 nM and 0.04 nM, respectively), facilitating antitumor T-cell responses (Stewart, 2015). Ibrutinib + anti-PD-L1 mAbs inhibited tumor cell growth and led to enhanced anti-tumor immune responses in mouse models (Sagiv-Barfi, 2015). This trial (PCYC-1135; NCT02403271) evaluates the safety and efficacy of ibrutinib + durvalumab in pts with PAC, breast cancer, and non-small cell lung cancer. Study details presented here focus on the cohort of pts with PAC. Methods: Key inclusion criteria include pathologically confirmed PAC, R/R disease (failed ≥ 1 prior systemic therapy), stage III-IV disease, ≥ 1 measurable lesion by RECIST 1.1 criteria, and adequate hematologic, renal, hepatic function. Key exclusion criteria include any history of central nervous system involvement; prior treatment with ibrutinib/BTK inhibitor or treatment with antibodies targeting PD-1, PD-L1, PD-L2, CD137, or CTLA-4; history of allogeneic organ transplant; or treatment with a strong cytochrome P450 3A inhibitor. Primary objectives are safety, tolerability, and efficacy of the combination; secondary objectives include pharmacokinetics and pharmacodynamic assessments of the combination. The phase 1b portion will assess the dose-limiting toxicities (DLTs) and determine the recommended phase 2 dose (RP2D). Ibrutinib will be administered at the standard dose with the potential for dose level reductions if DLTs occur in combination with durvalumab. After RP2D determination, enrollment in phase 2 will occur until a total of 130-160 pts (across all 3 disease cohorts) are treated. Enrollment for phase 1b began in March 2015. Clinical trial information: NCT02403271.
Bridging community and academic cancer centers using nurse navigation.
Authors: Miller Eleanor 
Published: February 2017

102 Background: The Penn Cancer Network was formed in the early 1990’s to bridge a connection between the community oncology setting and The University of Pennsylvania, an academic medical center. Aspects of the network contracts include cancer program assessment and development, accreditation preparation, and most recently dedicated access to cancer care via the network nurse navigator. This poster emphasizes the impact of a network nurse navigator has as a highly sought link between health systems, providers and patients to streamline patient referrals, with a formal process evolving over time. Methods: The establishment, growth and success of the referral process can be attributed to multiple efforts on behalf of the nurse navigator and administration, including but not limited to strong relationship development among nurse navigators and administrators at the hospitals and a formalized process developed by the nurse navigators using an online portal for referrals directly to the nurse navigator. Metrics are also maintained to demonstrate clinical and financial outcomes. Results: Since the establishment of a dedicated nurse navigator in 2010, referrals have increased year over year and two hospitals have since joined Penn Medicine, in part due to these strong relationships. Systematic chart reviews and data analysis have been completed annually to present to administration, with hundreds of patients being referred annually for second opinions, complex surgeries or clinical trials. A comprehensive financial analysis has been done to demonstrate the impact of these patient referrals on the health system, increasing annually. Conclusions: Access to the network nurse navigator has been emphasized as a major advantage to being a network hospital. A nurse navigator is well positioned to triage to subspecialties, assess patient and provider needs, and be knowledgeable in the operations of both systems. Data analysis has been paramount in demonstrating the impact of this program, both clinically and financially. This process could be done for formal network relationships or informal, but it certainly builds a great pattern to improve patient’s access to care.
Bringing provincial improvements to oral chemotherapy prescribing through co-ordinated regional initiatives.
Authors: Simanovski Vicky , Ahmad Noor , Kaizer Leonard , Redwood Erin , Vu Kathy , Fox Colleen , Meertens Elaine , Krzyzanowska Monika K. 
Published: February 2017

107 Background: Oral chemotherapy delivery is complex, making safe medication practices a high priority. Cancer Care Ontario, the provincial government agency responsible for continually improving cancer services in Ontario, undertook a jurisdiction-wide quality improvement initiative to ensure that all oral chemotherapy drugs are prescribed using Computerized Prescriber Order Entry (CPOE) or standardized Pre-printed Orders (PPO). The initiative was further enabled by changes to the provincial funding approach that flows facility funding for oral chemotherapy delivery. Methods: All 35 facilities prescribing chemotherapy in Ontario across 14 regions implemented strategies to work towards the common aim of reducing handwritten/verbal oral chemotherapy prescribing to zero by June 30th, 2015. Baseline audits were completed between Sept-Nov 2014; repeat audits were performed between Mar-May 2015. Each facility reported the number of patients that received an oral chemotherapy prescription, and the method of prescribing. Results: At baseline, 30% of audited prescriptions across the province were handwritten or verbal, which decreased to 9% by June 2015. Improvements were seen in thirteen of the 14 regions. Thirteen out of 35 facilities met the aim of 0 handwritten/verbal orders, with an additional 16 facilities seeing an improvement. Alignment with funding mechanisms, an early physician engagement strategy, and education of key stakeholders on CPOE systems were identified as key enablers to implementation. Conclusions: Though the goal of zero handwritten/verbal prescriptions was not met by all facilities, the initiative encouraged a change in implementing safe prescribing practices for oral chemotherapy. Further audits will assess that the gain was sustained and that the provincial goal is achieved. This initiative is part of a larger strategy to standardize care for systemic treatment patients and promote a culture of safety in hospitals. [Table: see text]