bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of laparoscopic stomach preserving surgery with sentinel basin dissection compared with standard gastrectomy with lymphadenectomy in early gastric cancer: A study protocol of a multicenter randomized phase III clinical trial (SENORITA trial).
Authors: Ryu Keun Won , Park Ji Yeon , Kim Young Woo , Nam Byung-Ho , Lee Young Joon , Jeong Sang-Ho , Park Ji-Ho , Hur Hoon , Han Sang Uk , Min Jae-Seok , An Ji Yeong , Hyung Woo Jin , Cho Gyu Seok , Jeong Gui Ae , Jeong Oh , Park Young-Kyu , Jung Mi Ran , Yoon Hong Man , Eom Bang Wool
Published: February 2017

TPS179

Background: Along with marked increase in early gastric cancer (EGC) in Eastern countries, there has been an effort to adopt sentinel node concept in EGC to reduce immediate postoperative complications and preserve gastric function. Based on the promising results from the previous quality control study prior to phase III trial, this prospective multicenter randomized controlled trial aimed to elucidate the oncologic safety of laparoscopic stomach-preserving surgery with sentinel basin dissection (SBD) compared to standard laparoscopic gastrectomy. Methods: This trial is an investigator-initiated, open-label, multicenter randomized controlled phase III trial with non-inferiority design. Patients diagnosed with a single lesion of clinical stage T1N0M0 gastric adenocarcinoma with a diameter of 3cm or less are eligible for the present study. A total of 580 patients (290 per each group) will be randomized to either laparoscopic stomach-preserving surgery with SBD or standard surgery. The primary end-point is 3-year disease-free survival (DFS) and the secondary endpoints include postoperative morbidity and mortality, quality of life, and 5-year DFS and overall survival. The qualified investigators who completed the prior quality control study are exclusively allowed to participate in this phase III clinical trial. Discussion: The proposed trial is expected to verify whether laparoscopic stomach-preserving surgery with SBD achieves the similar oncologic outcomes and improved quality of life compared to the standard gastrectomy in EGC patients. Clinical trial information: NCT01804998.
A study of the combination of oxaliplatin, capecitabine, and herceptin (trastuzumab) and chemoradiotherapy in the adjuvant setting in operated patients with HER2+ gastric or gastro-esophageal junction cancer (TOXAG study).
Authors: Abali Huseyin , Yalcin Suayib , Onal Huseyin Cem , Dane Faysal , Oksuzoglu Berna , Ozdemir Nuriye , Mertsoylu Huseyin , Artac Mehmet , Camci Celalettin , Karabulut Bulent , Bugdayci Basal Fatma , Budakoglu Burcin , Sendur Mehmet Ali Nahit , Goktas Burce , Ozdener Fatih , Calisgan Arzu
Published: February 2017

TPS182

Background: Trastuzumab in combination with chemotherapy has been shown to prolong survival of HER2+ esophago-gastric cancer patients. The primary aim of our study was to evaluate safety and tolerability of trastuzumab (T) in combination with oxaliplatine (O), capecitabine (C) and radiation (R) therapy in the adjuvant setting in curatively resected esophago-gastric cancer patients. Methods: Forty patients with IB or higher stages was planned to be recruited and here we report the interim analyses on 22. We would consider the study positive if at least 64.4% of patients could tolerate the therapy. Eligible patients received T 8 mg/kg intravenously (iv) on Day 1 of cycle 1 and 6 mg/kg iv on day 1 of every following 3-weekly cycle for 1 year as 17 cycles, with O 100 mg/m2 iv on Day 1 of cycles 1-3 and C 850 mg/m2 orally twice daily on days 1-14 of cycles 1-3 and on 5 days per week during chemo-radiotherapy. R was given at a total dose of 45 Gy divided into 25 doses on 5 treatment days per week for 5 weeks starting from the 1st day of cycle 4. Results The median age was 57.5 years (Min-Max: 35-74). Of 22 patients; 15 were male (68.2%), 21 (95.5%) had an ECOG PS score ≤ 1, 21 (95.5%) had D2 lymph node resection. There were 11 serious adverse events. Two patients died on therapy; 1 secondary to pulmonary thrombo-emboli, and the other had to cerebral ischemia (thought to be due to Behçet’s disease), and 7 died of progression. There were 6 dose reductions (1 for T, 2 for O and 3 for C), T was stopped in 1 patient, C was interrupted 8 times (mostly during radiotherapy). Patients who have completed 3 cycles of O, C, T and 4th and 5th cycles of chemo-radiation therapy with C and T were defined as tolerable. Out of 22 patients, 19 (86.4%) were tolerable (Chi Square test: p = 0.0623). Median survival time for interim analysis patients (n = 22) was 22 months (95% CI: 11-23 months). Conclusion T in combination with O, C and chemo-radiation with C and T was tolerable with the tolerability rate of 86.4%, in curatively resected HER2 + esophago-gastric cancer adjuvant treatment. Clinical trial information: NCT01748773.
KEYNOTE-062: Phase III study of pembrolizumab (MK-3475) alone or in combination with chemotherapy versus chemotherapy alone as first-line therapy for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Tabernero Josep , Bang Yung-Jue , Fuchs Charles S. , Ohtsu Atsushi , Kher Uma , Lam Baohoang , Koshiji Minori , Van Cutsem Eric
Published: February 2017

TPS185

Background: Pembrolizumab (pembro) is a monoclonal antibody against PD-1 designed to block its interaction with PD-L1 and PD-L2 and permit an antitumor immune response. In KEYNOTE-012, pembro showed a 22% ORR (RECIST v1.1, central review) and a manageable safety profile in patients (pts) with advanced gastric cancer. The randomized, phase 3 KEYNOTE-062 study (NCT02494583) is designed to compare the efficacy and safety of pembro alone or in combination with cisplatin + a fluoropyrimidine with those of cisplatin + a fluoropyrimidine as first-line therapy for PD-L1+/HER2– advanced gastric or GEJ adenocarcinoma. Methods: Key eligibility criteria include age ≥ 18 y, locally advanced or metastatic PD-L1+/HER2– gastric or GEJ adenocarcinoma, ECOG PS 0-1, no active autoimmune disease or brain metastases, and no prior therapy for advanced disease. Pts are randomized 1:1:1 to pembro 200 mg Q3W (arm 1), pembro + cisplatin 80 mg/m2 Q3W + 5-fluorouracil (5-FU) 800 mg/m2 on days 1-5 of each Q3W cycle (arm 2), or placebo Q3W + cisplatin + 5-FU (arm 3); 5-FU may be replaced with capecitabine 1000 mg/m2 twice daily on days 1-14 of each cycle. Randomization is stratified by region (Europe/North America/Australia vs Asia vs rest of world), disease status (locally advanced vs metastatic), and chosen fluoropyrimidine (5-FU vs capecitabine). Arm 1 is open label; in arms 2 and 3, assignment to pembro vs placebo is double blind. In all arms, treatment will continue for 35 cycles or until progressive disease, unacceptable toxicity, or pt/investigator decision. Response will be evaluated every 6 wk per RECIST v1.1 by central review and per RECIST adapted for immunotherapy response patterns; eligible pts may continue treatment beyond initial RECIST-defined progression. AEs will be assessed throughout treatment and for 30 d thereafter (90 d for serious AEs) and graded per NCI CTCAE v4.0. Pts will be followed for survival every 3 mo. OS and PFS per RECIST v1.1 are the primary study end points; secondary end points include ORR and duration of response. Enrollment in KEYNOTE-062 is ongoing and will continue until ~750 pts have enrolled. Clinical trial information: NCT02494583.
Multi-institutional phase II trial of single agent regorafenib in refractory advanced biliary cancers.
Authors: Soares Heloisa P. , Kothari Nishi , Mahipal Amit , Springett Gregory M. , Kim Jongphil , Tariq Fatima , Sanoff Hanna Kelly , Poklepovic Andrew Stewart , Kim Richard D.
Published: February 2017

TPS468

Background: Currently, there is no standard second line treatment for patients with advanced biliary tract cancer (BC) who have failed prior systemic therapy. Aberrant activation of the Ras/Raf/MEK/ERK pathway occurs in more than 60% of BC indicating the importance of this pathway in biliary carcinogenesis. Furthermore anti-angiogenic agents such as the VEGF-antagonist bevacizumab, and the multikinase inhibitor sorafenib have been tested in BC in the first line setting with modest activity. Regorafenib is an oral multi-kinase inhibitor that targets multiple membrane-bound and intracellular kinases including VEGF, the Ras/Raf/MEK/ERK and PDGFR- ß pathways. Given the pivotal role of these pathways in biliary cancer biology, the clinical evaluation of regorafenib represents a novel and rational approach to treat this disease. Methods: This is a multi-institutional phase II single arm single-stage design trial using regorafenib as single agent. Patients with histologically or cytologically-proven locally advanced or metastatic biliary tract carcinomas that failed no more than 2 prior line of systemic chemotherapy are eligible for this study. Patients must have measurable disease per RECIST 1.1 criteria and never been treated with VEGF inhibitors. Patients will receive regorafenib 160 mg daily (21 days on and 7 days off) and will be evaluated for response every 2 cycles (1cycle = 28 days). The study’s primary endpoint is 6 month overall survival. Secondary endpoints are to define disease control, progression-free survival and toxicity related to treatment. Correlative biomarker studies using plasma samples will be performed to investigate levels of 40 relevant proteins associated with the above-mentioned pathways in the attempt to identify predictive markers of drug benefit. As per September 2015, twelve of the 39 planned patients have been accrued for the study. In addition to Moffitt Cancer Center, this trial will enroll patients at the UNC Lineberger Comprehensive Cancer Center and VCU Massey Cancer Center. Clinical trial information: NCT02115542.
A phase Ia/Ib trial of trametinib in combination with sorafenib in patients with advanced hepatocellular cancer.
Authors: Soares Heloisa P. , Kim Richard D. , Kothari Nishi , Cooksey Jennifer , Springett Gregory M. , Mahipal Amit
Published: February 2017

TPS469

Background: MEK inhibitors have demonstrated preclinical activity in hepatocellular carcinoma (HCC). More importantly, in xenograft models, this class of inhibitors acts synergistically with sorafenib to inhibit tumor growth, prevent metastatic spread and increase survival. In preclinical models, sorafenib leads to overactivation of the MAPK pathway, which can be counterbalanced by the use of MEK inhibitors. Trametinib is a reversible, highly selective, allosteric MEK inhibitor. Methods: This is an open label, single group, phase I study with cohort expansion that utilizes the standard 3+3 design for dose escalation. The primary objective of this study is to determine maximally tolerated dose (MTD) of trametinib in combination with sorafenib as first-line systemic treatment for patients with locally advanced or metastatic HCC. Secondary objectives are to explore and characterize the safety and tolerability of this combination at the established MTD and to explore its efficacy profile. Up to 24 patients will be enrolled in 4 dose levels. Once the MTD is reached and/or the recommended dose for expansion is determined, an additional cohort of 10 patients with advanced HCC will be accrued. Only patients with Child-Pugh score A will be included. Trametinib will be administered orally daily beginning day 8 of cycle 1. Sorafenib will be administered twice daily beginning day 1 of 28 days cycle. Patients will get restaging scans every 2 cycles. Correlative studies between various biomarkers and clinical outcomes will also be performed. Biomarkers will be assessed in archival tumor tissue. The pre- and post-dose expression level of biomarkers including pan and phospho-Mek and Erk will be measured on peripheral blood mononuclear cells during treatment. Pre and post treatment biopsies will be performed for patients participating in the dose expansion cohort for correlative studies including gene expression. As per September 2015, 3 patients have been enrolled in this trial. ClinicalTrials.gov identifier: NCT02292173 Clinical trial information: NCT02292173.
A randomized, open-label phase II study of nanoliposomal irinotecan (nal-IRI)-containing regimens versus nab-paclitaxel plus gemcitabine in patients with previously untreated metastatic pancreatic adenocarcinoma (mPAC).
Authors: Dean Andrew , Chen Li-Tzong , Ramanathan Ramesh K. , Blanchette Sarah , Belanger Bruce , Adib Deyaa , Bayever Eliel
Published: February 2017

TPS482

Background: Two combination chemotherapy regimens have emerged as standard of care options for first-line treatment of mPAC: 5-fluorouracil (5-FU)/leucovorin (LV) + irinotecan + oxaliplatin (FOLFIRINOX), and nab-paclitaxel + gemcitabine. Nal-IRI (MM-398) is a nanoliposomal formulation of irinotecan. In a randomized phase 3 study (NAPOLI-1), of patients with mPAC who had been previously treated with gemcitabine-based therapy, nal-IRI + 5-FU/LV demonstrated its safety and significant clinical activity, increasing overall survival (OS) and progression-free survival (PFS) relative to 5-FU/LV. The goal of this current study is to determine the preliminary safety and efficacy of nal-IRI+ + 5-FU/LV with or without oxaliplatin as compared to nab-paclitaxel + gemcitabine in previously untreated patients with mPAC. Methods: This open-label, phase 2 comparative study will be conducted in two parts. Part 1 is a safety run-in of a nal-IRI+5-FU/LV + oxaliplatin regimen. The safety run-in will enroll small cohorts of patients following a traditional 3 + 3 dose escalation design to confirm the target dose of oxaliplatin (n = ~6-18). The primary objective of Part 1 is the safety and tolerability of nal-IRI + 5FU/LV + oxaliplatin. Part 2 is a randomized, efficacy study of a nal-IRI + 5-FU/LV + oxaliplatin regimen (Arm 1), the nal-IRI + 5-FU/LV combination that previously demonstrated efficacy in the NAPOLI-1 trial (Arm 2), versus a nab-paclitaxel + gemcitabine control arm (Arm 3) (n = ~156-168). The primary objective of Part 2 is to assess the efficacy of nal-IRI-containing regimens in first-line mPAC patients compared to nab-paclitaxel + gemcitabine using the progression-free survival (PFS) rate at 24 weeks as the primary endpoint. Secondary of part 1 is a PK study and Part 2 secondary endpoints will include OS, PFS, objective response rate (per RECIST, v1.1), decrease in CA19-9 levels and quality of life assessments. Clinical trial information: NCT02551991.
Statistical analysis of episensitization using transition probability functions and PFS2 for “ROCKET”, a two stage phase II study of RRx-001, a multi-epigenetic agent, investigating resensitization to irinotecan in colorectal cancer.
Authors: Abrouk Nacer , Reid Tony R. , Fisher George A. , Carter Corey Allan , Thambi Paul M. , Oronsky Bryan , Fanger Gary , Caroen Scott , Parker Christopher , Stirn Meaghan , Scicinski Jan
Published: February 2017

TPS775

Background: The development of resistance to chemotherapies in cancer leads to disease progression resulting in impaired survival. RRx-001, a ROS-mediated DNMT and HDAC inhibitor, may resensitize patients to previously effective, now refractory therapies, improving survival. A randomized two-stage Phase 2 trial of RRx-001 vs regorafenib (ROCKET) is underway to assess the impact of resensitization to irinotecan on overall survival in irinotecan refractory tumors. Transition Probability Functions (TPF) using Markov Chains have previously been used in clinical trials and provide a powerful tool for resensitization analysis. Methods: Patients with metastatic colorectal cancer who previously responded, then progressed on irinotecan-based therapies, with or without bevacizumab, cetuximab or panitumumab and an ECOG PS 0-1 are randomized to receive RRx-001 1x/week or regorafenib until progression or unacceptable toxicity in Stage 1. Patients then advance to Stage 2 to receive irinotecan-based therapies. This trial is designed to detect an increase in median OS of 3 mo., corresponding to a 33% reduction in risk of death. The primary endpoint, overall survival (OS), employs a two-sided log-rank test to compare treatment groups. The hazard ratio and its 95% CI are derived from the Cox proportional hazards model. Kaplan-Meier survival curve estimates are graphically depicted by treatment group. Secondary endpoints include PFS, PFS2 and Transition Probability Functions to address the resensitization hypothesis, KRAS or p53 status dependence. The analysis of PFS2, defined as time to progression (or death) from randomization to progression in Stage 2 (post Irinotecan therapy) is a key secondary endpoint and its analysis uses the standard two-sided log-rank test. TPF estimates will be derived from the Markov Chain transition probability matrix. The study should provide compelling evidence in support of the ability to return to previously beneficial chemotherapy treatment. Recruitment is ongoing. Clinical trial information: NCT02096354.
The ATOM trial: A multicenter, randomized phase II study of modified FOLFOX6 plus bevacizumab and modified FOLFOX6 plus cetuximab for colorectal cancer with liver-limited metastases.
Authors: Emi Yasunori , Muro Kei , Yamanaka Takeharu , Katayose Yu , Uetake Hiroyuki , Sugihara Kenichi , Kakeji Yoshihiro , Unno Michiaki , Hyodo Ichinosuke , Tomita Naohiro , Maehara Yoshihiko
Published: February 2017

TPS777

Background: It remains unresolved which antibody, anti-vascular endothelial growth factor or anti-epidermal growth factor receptor antibody, is the best targeted agent to combine with chemotherapy for patients having liver-limited metastases of KRAS Exon 2 or RAS wild-type colorectal cancer. Methods: The ATOM trial is a Japanese multicenter, randomized phase II study comparing modified FOLFOX6 plus bevacizumab with modified FOLFOX6 plus cetuximab in patients with unsuitable liver metastases for resection (5 or more liver metastatic lesions and/or maximum tumor diameter > 5cm). Patients are enrolled and randomly assigned to receive either treatment in 1:1 ratio from May 2013 to April 2016. Stratification factors for randomization are synchronous or metachronous liver metastases, number (1–4 or ≥ 5) and size ( ≤ 5 cm or > 5 cm) of metastatic lesions, and adjuvant chemotherapy with or without oxaliplatin-containing regimen. All patients are to be followed up to March 2017. Primary endpoint is progression-free survival (PFS). We employed a selection design based on hazard ratios. Planned sample size is 120 patients with 84 estimated PFS events based on the hypothesis to select the superior treatment with the 75.0 % selection probability if the difference of both treatments is a 1-year PFS rate of 5% and the inferior treatment has a 1-year PFS rate of 50%. Secondary endpoints are response rate, tumor shrinkage at week 8, liver resection rate, time to treatment failure, overall survival, quality of life, and adverse events. Exploratory endpoints include pathologic and morphologic assessments, which will be investigated in collaboration with radiologists and pathologists. The plasma factors relating to tumor angiogenesis are assessed sequentially to explore the association with treatment efficacies. As of Aug 20th 2015, 102 patients were enrolled. The results from this trial will show which targeted agents should be used to treat liver-limited diseases from colorectal cancer with WT RAS tumor. Clinical trial information: NCT01836653.
A randomized, phase II study of high-risk colorectal cancer patients (stage IIIC) treated with either regorafenib or standard of care (no treatment) after adjuvant FOLFOX.
Authors: Cartwright Thomas H. , Cohn Allen Lee , Richards Donald A.
Published: February 2017

TPS779

Background: Standard adjuvant treatment for colorectal cancer (CRC) is usually a fluoropyrimidine or FOLFOX. However the relapse rate for stage IIIC patients is high with a median 5 year survival of only 28%. The multi-kinase inhibitor regorafenib has been shown to significantly improve progression-free and overall survival (PFS; OS) compared with placebo as 3rd-line or later therapy for patients with metastatic CRC. Thus it is of interest to explore whether adding regorafenib to standard adjuvant therapy may be able to reduce the high relapse rates in patients with stage IIIC CRC. In addition, texture analysis (spatial variations in pixel intensity) of computed tomography (CT) scans may be a useful prognostic tool for determining risk of recurrence. Methods: The current study is designed to compare the efficacy and safety of adding 6 cycles of regorafenib versus standard of care (no additional systemic therapy) following 6 months of adjuvant FOLFOX in patients with high risk (stage IIIC) CRC. The primary endpoint is to find the starting dose of regorafenib that allows ≥ 75% of patients to complete therapy at the full dose following adjuvant FOLFOX. Secondary endpoints include estimation of disease-free survival (DFS) and OS, assessment of adverse events, and identification of associations between texture analysis results and DFS. The study will enroll 264 adult patients with stage IIIC CRC with no evidence of disease by CT scan after completion of 6 months of adjuvant FOLFOX therapy. The first 50 patients will be randomized to a starting dose of either 120 mg or 160 mg of regorafenib daily for 3 weeks followed by 1 week rest for a total of 6 cycles. Safety analyses will be performed after the first 26 patients complete 3 cycles of study treatment and again after 50 patients. Based on this determination, the remaining 214 patients will be randomly assigned (2:3) to receive 6 cycles of regorafenib at the selected starting dose or standard of care (no additional treatment). CT scans will be sent for texture image analysis and results correlated with DFS. Clinical trial information: NCT02425683. Clinical trial information: NCT02425683.
A multinational, randomized, phase III trial of XELIRI (+bevacizumab) versus FOLFIRI (+bevacizumab) as the second-line chemotherapy for metastatic colorectal cancer: Asian XELIRI project (AXEPT).
Authors: Muro Kei , Kim Tae Won , Park Young Suk , Uetake Hiroyuki , Nishina Tomohiro , Nozawa Hiroaki , Matsumoto Hiroshi , Yamazaki Kentaro , Han Sae-Won , Lee Keun-Wook , Deng Yanhong , Buyse Marc E. , Satoh Taroh , Ryoo Baek-Yeol , Shen Lin , Iwasa Satoru , Morita Satoshi , Sakamoto Junichi , Xu Rui-hua
Published: February 2017

TPS780

Background: Life-prolonging systemic therapy such as chemotherapy (FOLFOX, XELOX, FOLFIRI, 5-FU/LV) with / without molecular targeted agents (bevacizumab, afilibercept, cetuximab, panitumumab) are important treatment for metastatic colorectal cancer (mCRC). On the other hand, it is required to establish an evidence of convenient therapy including oral anticancer agent which is expected lower risk of safety. XELIRI was already examined by various doses in this decade, and result of AIO 0604 was regarded as one of the most appropriate regimen. The BIX phase II study showed the tolerability and promising efficacy of the AIO regimen for Japanese mCRC patients (Hamamoto Y, et al. Oncologist 2014). Methods: Asian XELIRI Project (AXEPT) is an East Asian collaborated, open label, randomized phase III clinical trial designed to demonstrate the non-inferiority of XELIRI (+bevacizumab) to the standard of care FOLFIRI (+bevacizumab) as the second-line chemotherapy in patients with mCRC. The primary endpoint is median overall survival. The secondary endpoints are progression-free survival, time to treatment failure, overall response rate, disease control rate, relative dose intensity, safety, correlation between UGT1A1 polymorphisms (*28, *6) and safety. Eligible patients were 20 years of age and older, had histologically proven CRC, ECOG performance status 0-2, adequate organ function, progression or difficult to continue after first line regimen. Patients were randomized 1:1 to standard FOLFIRI (+bevacizuamb 5mg/kg day1), repeated every 14 days (Group A) or XELIRI, Irinotecan 200mg/m2 day1, and capecitabine 1600mg/m2 day 1-14 (+bevacizumab 7.5mg/kg day1), repeated every 21 days (Group B). A Total of 464 events were needed to show non-inferiority with a two-sided α of 0·05 and a power of 80%, a target sample size of 600 patients was required. (The 95% CI upper limit of the hazard ratio was pre-specified as less than 1.3.). Enrollment has started in December 2013. As of August 2015, 98 centers in the Japan, South Korea and China are participating in this trial. Clinical trial information: NCT01996306. UMIN000012263. Clinical trial information: NCT01996306.
Immunomodulatory switch maintenance therapy in metastatic colorectal carcinoma: The phase III IMPALA study.
Authors: Cunningham David , Scheithauer Werner , Zurlo Alfredo , Salazar Ramon , Ducreux Michel , Waddell Tom Samuel , Tournigand Christophe , Sobrero Alberto F. , Van Cutsem Eric , Arnold Dirk
Published: February 2017

TPS785

Background: The Toll-like receptor 9 agonist MGN1703 was compared to placebo in 59 metastatic CRC (mCRC) patients with disease control after standard induction chemotherapy in the double-blind randomized phase 2 IMPACT study. MGN1703 showed a superior effect over placebo, with a hazard ratio (HR) for the primary endpoint “PFS on maintenance” of 0.55 (p = 0.041) by local assessment and 0.56 (p = 0.070) by independent radiological review. Exploratory PFS analyses identified patients with objective RECIST response, normalized CEA and presence of activated NKT cells at the end of induction treatment to benefit the most from MGN1703. The OS evaluation showed a HR of 0.40 (median 24.5 vs. 15.1 months) for patients with RECIST response after induction therapy. Furthermore, at time of IMPACT study closure, 4 MGN1703 patients were still without progressive disease and continued treatment in compassionate use. As of August 2015, 3 patients were still receiving MGN1703 treatment in excess of three years (47-55 months), with 2 objective responses ongoing over 46 months. Methods: The international, multicenter, open-label phase 3 IMPALA study is conducted in collaboration with the AIO, TTD and GERCOR cooperative groups. In IMPALA, mCRC patients having achieved an objective tumor response following any type of first line induction therapy are randomized to receive MGN1703 switch maintenance monotherapy in the experimental arm or local standard of care in the control arm. In case of relapse, patients will reintroduce induction treatment whenever feasible, with those in the experimental arm continuing to receive MGN1703 therapy in the weeks without infusional chemotherapy. The primary endpoint of the study will be OS. Secondary endpoints include PFS, response rates, safety, and QoL in selected centers. Induction treatment, CEA and activated NKT at baseline are stratification factors and will be prospectively assessed. All randomized patients take part in a comprehensive immune monitoring plan evaluating cytokines and chemokines in serum and the activation status of immune cell populations. Recruitment started in September 2014 and the study is expected to recruit 540 patients within 24 months in 8 European countries. Clinical trial information: NCT02077868.
The ORCHESTRA trial: A phase III trial of adding tumor debulking to systemic therapy versus systemic therapy alone in multi-organ metastatic colorectal cancer (mCRC).
Authors: Gootjes Elske C. , Buffart Tineke E , Tol M.P. , Burger J , Grunhagen Dirk J. , van der Stok Eric P , Meijerink Martijn R. , Ten Tije Albert J. , Meerten Esther Van , van de Ven Peter M , Nuyttens Joost , Haasbeek Cornelis J , Verhoef Cornelis , Verheul Henk M.W.
Published: February 2017

TPS788

Background: In the current multidisciplinary approach of mCRC, local treatment of oligometastases is common practice. Results of large case series of selected patients treated with complete surgical resection of metastatic lesions suggest that this approach substantially improves survival rates to around 30-60%. Other techniques such as radiofrequency or microwave ablation (RFA, MWA), transarterial chemoembolization (TACE) or radiotherapy can also be applied in local treatment. Curative treatment options are generally not available for patients with extensive hepatic and/or extrahepatic mCRC. These patients primarily receive palliative systemic treatment consisting of combination chemotherapy as well as targeted agents. So far, reports on the benefit of local treatment for metastases in multi-organ mCRC have major limitations, including being small, non-randomized, single-center and retrospective. The benefit from local treatment of metastases for these patients should be established to allow for interruption of the standard systemic therapy and exposure to possible adverse events from local treatment. Methods: The ‘ORCHESTRA’ trial is a randomized multicenter clinical trial for patients with multi-organ mCRC, comparing the combination of chemotherapy and maximal tumor debulking versuschemotherapy alone (NCT01792934). We will examine the interplay of both efficacy and toxicity for the combination of systemic chemotherapy and locoregional therapy. Our study design incorporates systemic as well as local therapy in the experimental arm and combines local treatment modalities to pursue maximal tumor debulking. We aim to improve overall survival of patients with multi-organ mCRC by maximal tumor debulking after induction chemotherapy with at least six months. A total of 478 patients will be included to meet the primary endpoint (power 80%, type I error rate 5%). We define local treatments feasible when they can be performed within a 3-month time period to prevent extensive delay of systemic therapy. Currently, 60 patients are included in 22 participating Dutch hospitals. Clinical trial information: NCT01792934.
KEYNOTE-177: First-line, open-label, randomized, phase III study of pembrolizumab (MK-3475) versus investigator-choice chemotherapy for mismatch repair deficient or microsatellite instability-high metastatic colorectal carcinoma.
Authors: Diaz Luis A. , Le Dung T. , Yoshino Takayuki , Andre Thierry , Bendell Johanna C. , Zhang Yinghua , Lam Baohoang , Koshiji Minori , Jäger Dirk
Published: February 2017

TPS789

Background: Mismatch repair deficient (dMMR) tumors are characterized by high mutational load and lymphocyte infiltration and may be good candidates for immune checkpoint blockade. Pembrolizumab is a monoclonal antibody against PD-1 that is designed to block its interaction with PD-L1 and PD-L2 and thus allow an antitumor immune response. In the KEYNOTE-016 proof-of-concept study, pembrolizumab showed promising antitumor activity against dMMR tumors in patients (pts) with treatment-refractory metastatic colorectal carcinoma (mCRC). KEYNOTE-177 is an international, randomized trial designed to evaluate the efficacy and safety of pembrolizumab compared with standard-of-care (SOC) chemotherapy in the first-line setting for dMMR or microsatellite instability-high (MSI-H) mCRC. Methods: Key eligibility criteria include age ≥ 18 y, confirmed MSI-H or dMMR mCRC, ECOG PS 0-1, no active autoimmune disease or brain metastases, and no prior therapy for metastatic disease. Pts will be randomized 1:1 to receive either pembrolizumab 200 mg Q3W or investigator’s choice of SOC chemotherapy. Chemotherapy must be chosen prior to randomization; options include mFOLFOX6 or FOLFIRI alone or in combination with bevacizumab or cetuximab. Treatment will continue until PD, unacceptable toxicity, pt/investigator decision, or completion of 35 cycles (pembrolizumab only). Response will be evaluated every 9 wk per RECIST v1.1 by central review and per RECIST adapted for immunotherapy response patterns. Eligible pts may continue pembrolizumab beyond initial RECIST-defined progression. Pts in the SOC arm who have PD and meet crossover criteria may be eligible to receive pembrolizumab for up to 17 treatment cycles. AEs will be assessed throughout treatment and for 30 d thereafter (up to 90 d for serious AEs) and graded per NCI CTCAE v4.0. Pts will be followed for survival every 9 wk. PFS per RECIST v1.1 is the primary end point; OS and ORR are key secondary end points. Other end points include duration of response and health-related quality of life. Planned enrollment in KEYNOTE-177 is 270 pts.
Improving the treatment of patients with low-risk neutropenic fever: A quality improvement project at the Cleveland Clinic Taussig Cancer Institute (TCI).
Authors: Goodman Lindsey Martin , Lau Jessica , Gallagher Erika M. , Moeller Machelle , Best Carolyn , Stevenson James
Published: February 2017

101

Background: NF is an oncologic emergency and has historically resulted in inpatient (inpt) management. The Multinational Association for Supportive Care in Cancer (MASCC) score can be used to identify NF pts at LR for complications who can be safely managed in the outpatient (outpt) setting. Despite established guidelines supporting outpt management of LRNF, provider awareness is low and inpt admission for intravenous antibiotics (abx) continues to be standard of care. Methods: A multidisciplinary team performed a QI project to improve management of LRNF (baseline cohort of LRNF pts treated from Jan - Mar 2014, N = 13). Inpt provider education began in the Q2 2014. Providers calculated MASCC scores for pts with non-leukemia hematologic malignancies and solid tumors at the time of admission. Data was collected in a prospectively maintained registry. Pts identified as LR by MASCC score were admitted under observation and placed on oral abx. If exclusion criteria and social barriers were not identified, discharge (dc) within 24 hrs of admission was planned. To ensure pt safety, close follow up included phone follow up within 48 hrs of dc and a provider visit within 72 hrs. Results: 52 pts were admitted to the TCI inpt oncology unit with NF from Oct 2014 - June 2015. 34 pts (65%) had LRNF (MASCC score, < 21). 9 pts (26%) were dc within 24 hrs. Only 2 LRNF pts had a culture proven infection – both Enterococcus UTIs. 3 pts required readmission for reasons other than scheduled inpt chemotherapy: 1 high risk pt for new symptoms and 2 LRNF pts (22%) dc within 24 hours for recurrent fever; neither had culture proven infection. Pts with LRNF had an average LOS of 3.3 days compared to 6.2 days in the historical cohort. There were no deaths due to NF in either cohort. Conclusions: Calculating a MASCC score at admission identifies pts who are potential candidates for outpt, oral abx therapy. This pilot study demonstrates that provider education followed by implementation of a system to ensure close follow up may result in earlier dc for LRNF pts without increasing risk of complications or readmission. Further follow up will occur Q3 2015 and data will be presented on changes in cost measures.
The Kaiser Permanente Breast Cancer Survivorship National Clinical Algorithm: Regional variation in implementation processes/strategies within an integrated health care system.
Authors: Lagana Michele , Hahn Erin Elizabeth , Schottinger Joanne E. , Kutner Susan E , Littlewood Mark B
Published: February 2017

104

Background: Kaiser Permanente (KP) is an integrated healthcare system providing comprehensive services to over 10 million members. The KP Interregional Breast Care Leaders, a multidisciplinary clinician group, developed a comprehensive evidence/consensus-based algorithm for breast cancer survivors, the KP Breast Cancer Survivorship National Clinical Algorithm (BCSNCA). The BCSNCA is intended to reduce variation in medical and psychosocial surveillance and improve outcomes by providing guidance to locally implemented survivorship programs, ie, recommendations for surveillance, late effects management, and risk reduction. As a quality improvement project, we evaluated regional/ facility level implementation. Methods: Qualitative data on BCSNCA implementation was collected from key informant interviews with oncology providers for 20 sites in 6 regions: Georgia, Colorado, Hawaii, Southern (KPSC) and Northern California (KPNC), and Mid-Atlantic, and by attending BCSNCA meetings. Implementation activities were recorded, categorized, and compared to BCSNCA. Results: Facilities in 3 regions implemented discrete BCSNCA components: Northwest and Georgia facilities implemented dedicated survivorship clinics; a KPSC facility piloted a nurse navigator standardized psychosocial assessment; KPNC implemented local guidelines, similar to the BCSNCA. One region has not implemented; Georgia implemented all BCSNCA components. There is variation within each region. Implementation drivers include available resources, competing QI priorities/leadership preferences, and adaptability of extant programs. Conclusions: We found variation between and within regions. The BCSNCA content accommodates variation in implementation, guided by a complex set of factors, including resource availability, leadership preferences, and local organizational goals. Even in integrated systems, the need for locally driven guideline adaptation is critical. Next step: assessment of BCSNCA components on patient-level outcomes.
Recommendations for the delivery of focal tumor ablation services.
Authors: Hertz Sherrie , McKay Cassandra , Wang Jonathan , Baldassarre Fulvia , Wong Amanda , Langer Deanna , Kachura John , Dobranowski Julian
Published: February 2017

106

Background: The objective of this work was to develop recommendations for the organization and delivery of focal tumor ablation services. New, minimally-invasive ablation technologies such as radiofrequency ablation (RFA), microwave ablation (MWA), and transcatheter arterial chemoembolization (TACE) offer treatment options for patients with a variety of cancers. These emerging therapies can improve patient care (minimize side-effects, offer more rapid recovery with comparable or enhanced outcomes) compared to traditional approaches. However, they are often resource intensive, necessitating a planned system-level approach to ensure appropriate access to high quality services while optimizing care and resource utilization. Methods: This work was led by an Advisory Committee with regional, clinical, administrative and patient representatives and was based on best available evidence, current practice in Ontario, Canada, and guidance from other jurisdictions and experts in the field. A variety of data sources (clinical, system, provider), consultation with external stakeholders and consensus building supported the final recommendations. Results: Thirteen recommendations were developed. Clinical criteria are detailed for RFA for liver, kidney and lung tumors and TACE for hepatocellular carcinoma. MWA is not recommended for lung, liver or kidney tumors. System recommendations include infrastructure (capital equipment, multidisciplinary management and case conference review), the importance of volume-related expertise, and oversight for funding and collaborative planning. Results were broadly disseminated through 12 stakeholder groups connecting with over 40,000 individuals. Conclusions: A systematic approach to understanding opportunities and challenges for focal tumor ablation therapies resulted in multi-level recommendations spanning clinical criteria through to quality oversight. These recommendations will support improvements in care delivery in daily practice and at the system level.
A prospective study of an inpatient febrile neutropenia clinical practice guideline in oncology patients.
Authors: Le Tri Minh , Thomas Tanya , Reuss Joshua , Degennaro Gina , Daniels Elizabeth , Li Jin , Smolkin Mark , Keng Michael Kenneth
Published: February 2017

114

Background: Febrile neutropenia (FN) is a common complication in oncology patients and is associated with significant morbidity and mortality if untreated. Because of this, it is regarded as a medical emergency. FN treatment guidelines universally recommend the prompt initiation ( < 60 minutes) of intravenous antibiotic therapy. We hypothesized that a quality initiative project creating a new FN clinical practice guideline (CPG) would reduce the time to antibiotic administration (TTA) for inpatient oncology patients with FN. Methods: This prospective study compared patients diagnosed with an initial episode of FN (4/2015-8/2015) with historical controls (4/2013-8/2013) on an inpatient oncology floor at a tertiary care academic hospital. Interventions included the development of an institutional CPG which standardized the definition of FN, implementation of a new clinical workflow, creation of education sessions for LIP’s and RN’s, and creation of an electronic FN order set. The primary outcome was TTA, with target goal being < 60 minutes from the onset of fever. Secondary outcomes included time to antibiotic order, need for ICU care, and 30-day mortality. P-values were calculated using a chi-square test. Results: In total, 31 consecutive FN episodes were observed over the 5-month study period. The median TTA decreased from 112 minutes in 2013 to 37.5 minutes in 2015 (p < 0.001). 30/31 (97%) patients in the 2015 group had their antibiotics ordered within 60 minutes vs 14/22 (64%) in 2013 (p = 0.002). 26/31 (84%) patients in the 2015 group had antibiotics administered within 60 minutes vs 4/22 (18%) in 2013 (p < 0.001). There was no significant difference in need for ICU care (16% in 2015 vs 9% in 2013, p = NS) or 30-day mortality (6% in 2015 vs 5% in 2013, p = NS). Conclusions: The inpatient FN CPG is a significant quality improvement initiative that has shown significant improvements in TTA. We were able to demonstrate value by a significant decrease in median TTA compared to historical controls with a significantly increased percentage of patients having both antibiotics ordered and administered within 60 minutes. In our cohort of patients, no significant differences were noted in rates of ICU care or 30-day mortality.
Data collection for care pathways in the Cleveland Clinic Health System.
Authors: Glass Katherine , Cummings Chad W , Shapiro Marc A. , Urbanek Dennis , Bolwell Brian James
Published: February 2017

115

Background: Care pathways are established methods of reducing healthcare costs and disparities in oncology care. To demonstrate their impact, health systems must measure and report data on care pathway adherence and outcomes in near real-time. Automating data abstraction across a health system for oncology is difficult due to the amount and detail of data required. Manual abstraction of data is considered slow and costly. Many consider Electronic Medical Record (EMR) integration of care pathways essential in order to successfully implement and assess. Methods: 7 medical oncology care pathways and 45 medical oncologists across the health system were selected for a pilot study to assess the feasibility of implementing care pathways throughout the enterprise. The pilot study also allowed for testing of data collection capabilities. Patients eligible for the care pathways were prospectively identified by manual review of physician calendars. A small number of data points were manually abstracted from the patient EMR at the time of identification. Endpoints of interest, such as hospitalization rates, chemotherapy administered, time to treatment, and costs of care were reconciled through pre-existing databases within pharmacy, research, and finance. Tumor registry data identified a retrospective cohort. Results: Over 1,000 patients were prospectively identified for the care pathway pilot between 1/1/2014 and 12/31/2014. The tumor registry identified 700 additional retrospective patients. The rapid analyses possible as a result of these efforts demonstrated physician adherence, improved patient outcomes, and significant cost savings. In one example, a care pathway for metastatic non-small cell lung cancer reduced charges by more than $98,000/patient by recommending patients receive one standardized chemotherapeutic regimen. Conclusions: Timely data collection for oncology care pathways is feasible and cost effective without EMR integration. Manual identification of patients combined with pre-existing data sources allowed for near-real time analysis of care pathways and provided valuable information about care pathway impact. Institutions can implement and assess care pathways with resources already available to them.
Exploring providers and survivors perceptions of dedicated cancer survivorship care clinics.
Authors: Palos Guadalupe R. , Wagner Richard W , Hebdon Megan , McComb Sara , Gilmore Katherine Ramsey , Chapman Patricia , Rodriguez Maria Alma
Published: February 2017

117

Background: The complex physical and psychological sequelae faced by cancer survivors require methodical follow-up care. A growing body of evidence suggests clinics and providers dedicated to survivorship care is a promising approach for addressing these needs. Yet there is limited published data of survivors and providers' perceptions of dedicated survivorship care. This study’s objective was to ascertain the strengths and weaknesses of clinical services provided in survivorship clinics. Methods: This study used a mixed-methods approach with stratified purposive sampling in the breast, genitourinary, and head/neck survivorship clinics. Characteristics used for stratification included: disease site, staffing characteristics, and clinical infrastructure. Semi-structured interviews were conducted with survivors and stakeholders, i.e. providers and executive leaders. Staff trained in qualitative methods conducted the interviews. Standardized questions focused on: 1) overall impression of the experience, 2) perceptions of the survivorship care plan (SCP), and 3) recommendations for improving clinical services. A brief survey collected demographic and clinical data. De-identified interviews were audio-recorded, transcribed verbatim, and analyzed to confirm themes. Descriptive statistics were used to summarize all data. Results: A total of 52 participants (36 survivors and 16 stakeholders) were interviewed. Overlapping themes centered on value, continuity of care, and uncertainty about SCPs. Survivors often reported not being able to remember any details of the SCP. Providers felt “patients really like coming here…it’s not as stressful” while survivors reported finding value in receiving “coaching for having a better lifestyle”. Both groups discussed resistance to the survivorship transition process, particularly providers as illustrated in a statement that “they [survivors] are the best part of their day. Conclusions: Dedicated survivorship clinics were perceived as being valuable by both providers and survivors, despite challenges associated with services. Our findings suggest further work is warranted to better understand the nuances of survivorship care and clinics.