bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of adjuvant chemotherapy after neoadjuvant chemoradiotherapy for esophageal cancer.
Authors: Shridhar Ravi , Huston Jamie , Meredith Kenneth L 
Published: March 2017

92 Background: The use of adjuvant chemotherapy (AC) after neoadjuvant Chemoradiotherapy (NCR) and surgery for esophageal cancer is controversial. The purpose of this study is determine if AC is associated with an overall survival (OS) benefit after NCR. Methods: The National Cancer Database was queried to identify esophageal cancer patients who underwent NCR and surgery between 2006 and 2013 and stratified by treatment with AC. Propensity score matching was utilized against age, pathologic tumor and nodal stage, histology, and margin status. Kaplan-Meier and log-rank analysis was used to determine OS benefit. Univariate (UVA) and multivariate (MVA) was performed with Cox proportional hazard ratio analysis. Results: We identified 1816 patients. AC was associated with improved OS. The median and 3-year OS for AC versus none was 36.4 months and 50% versus 30.9 months and 45%, respectively, (p = 0.02), however, the benefit was restricted to node positive (N+) patients. The median and 3-year OS for AC versus none in N+ patients was 31 months and 44% versus 26 months and 36%, respectively, (p = 0.03). UVA revealed that AC only benefitted patients with N+, R0 resection, and adenocarcinoma. UVA revealed that age, pathologic T3-4, N+, high grade, and R1 resection were associated with increased mortality, while removal of > 10 nodes and AC was associated with decreased mortality. MVA revealed that age, pathologic T3-4, N+, high grade, and R1 resection were associated with increased mortality, while removal of > 10 nodes was associated with decreased mortality. MVA revealed that AC was not prognostic for OS in all patients nor in N+ patients. Conclusions: This is the largest analysis on the use of AC after NCR and surgery for esophageal cancer. While there is an OS benefit favoring AC, the benefit is restricted to N+ patients. However, no benefit to AC was seen on MVA. Clinical trials are needed to address the role of AC after NCR in esophageal cancer.
Pressurized intraperitoneal aerosol chemotherapy with low-dose cisplatin and doxorubicin (PIPAC C/D) in patients with gastric cancer and peritoneal metastasis (PIPAC-GA1).
Authors: Struller Florian , Horvath Philipp , Solass Wiebke , Weinreich Frank Jurgen , Konigsrainer Alfred , Reymond Marc A 
Published: March 2017

99 Background: Efficacy of 2nd and 3rdline chemotherapy in recurrent gastric cancer with peritoneal metastasis (RGCPM) is limited. We assessed the feasibility, safety and activity of intraperitoneal chemotherapy as PIPAC C/D in RGCPM after > 1 line of intravenous chemotherapy. Methods: Open-label, single-arm, Phase II ICH-GCP Clinical Trial (NCT01854255) Patients were scheduled for 3 courses q42 days of low-dose PIPAC with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2. Primary endpoint was objective tumor response (RECIST 1.1). Secondary endpoints were safety (CTCAE 4.0), histological tumor regression (PRGS) and overall survival. Results: 25 patients were enrolled. 10/25 (40 %, ITT) patients had an OTR. Complete or major regression on histology was observed in 9/12 (75 %) patients who underwent at least 2 PIPAC cycles. Mean overall survival was 8.4 months (13.1 months in patients with PCI < 12). There were no treatment-related deaths, no grade 4 toxicity and four (16%) grade 3 toxicities. Conclusions: PIPAC C/D is well tolerated and active in patients with RGCPM. Survival is encouraging. Randomized controlled trials should now be designed. Clinical trial information: NCT01854255. [Table: see text]
CheckMate 577: A randomized, double-blind, phase 3 study of nivolumab (Nivo) or placebo in patients (Pts) with resected lower esophageal (E) or gastroesophageal junction (GEJ) cancer.
Authors: Kelly Ronan Joseph , Lockhart Albert C. , Jonker Derek J. , Melichar Bohuslav , Andre Thierry , Chau Ian , Clarke Stephen John , Cleary James M. , Doki Yuichiro , Franke Fabio Andre , Kitagawa Yuko , Mariette Christophe , Montenegro Paola Catherine , Roca Enrique Luis , Ciprotti Marika , Moehler Markus 
Published: March 2017

TPS212 Background: Chemoradiotherapy (CRT) followed by surgical resection is a current standard of care (SOC) for pts with E/GEJ cancer, with 3- and 5-year survival rates ranging from 30% to 40%. Currently, no effective adjuvant SOC is available following resection. Expression of programmed death-1 (PD-1) ligands 1/2 (PD-L1/L2) has been associated with a poor prognosis in E/GEJ cancer, suggesting that PD-1 inhibition may improve outcomes. Nivo is a fully human IgG4 monoclonal antibody that targets PD-1, with demonstrated survival benefit in multiple tumor types and long-term responses in some patients. A phase 1/2 study of nivo monotherapy in chemotherapy-refractory pts with gastric/E/GEJ cancer demonstrated tumor regression, a median overall survival (OS) of 5 months, and a 12-month OS rate of 36% in pts with PD-L1+ and PD-L1- tumors (Janjigian Y, et al. J Clin Oncol. 2016;34:suppl; abstract 4010). This multinational, double-blind, phase 3 trial will evaluate nivo as an adjuvant therapy for pts with resected E/GEJ cancer (CheckMate 577; NCT02743494). Methods: In this study, an estimated 760 pts aged ≥ 18 years with stage II/III E/GEJ cancer are randomized to receive nivo or placebo. Prior to randomization, pts must have completed preoperative CRT followed by surgery and been diagnosed with residual pathological disease after being surgically rendered free of disease with negative margins following complete resection. Pts with stage 4 resectable disease, cervical esophageal cancer, or those who have not received concurrent CRT prior to surgery are not eligible for study enrollment. Primary endpoints are OS and disease-free survival. The secondary endpoint is OS rate at 1, 2, and 3 years. Clinical trial information: NCT02743494.
A phase II trial of neoadjuvant chemotherapy with docetaxel/cisplatin/capecitabine in thoracic esophageal squamous cell carcinoma.
Authors: Wu Xiaobin , Ling Jiayu , Li Shanshan , Xiang Jun , Deng Yanhong , Peng Junsheng 
Published: March 2017

TPS216 Background: The Optimal care for resectable squamous cell carcinoma of thoracic esophagus is uncertain. Effecacy of cisplatin-based two agent chemotherapy as neoadjuvant treatment remains limited. The combination of docetaxel, cisplatin, and capecitabine (DCX) for squamous cell carcinoma of thoracic esophagus in neoadjuvant set has not been investigated. Here, we conducted a phase II study to assess the efficacy and safety of neoadjuvant chemotherapy with modified DCX followed by surgery in patients with resctable thoracic Esophageal Squamous Cell Carcinoma. Methods: This is a single-arm prospective phase II study in Chinese patients. The main inclusion criteria are as follows: 1) Histologically proven squamous cell carcinoma of thoracic esophagus, T2-3, N0-2, T4aN0, M0 (UICC 7th edition); 2) age: 18-75 years, ECOG PS 0-1; 3) Enteral or parenteral feeding planned before the start of treatment if oral calorie intake < 1200 kcal; 4) written informed consent. Neoadjuvant modified DCX regimen consists of docetaxol 60mg/m2 iv d1 and cisplatin 30mg/m2 iv d1-2 and capecitabine 850mg/m2 bid po d1-14 repeated every 21 days for 4-6 cycles, followed by Ivor Lewis Esophagectomy. Primary endpoint is 2-year overall survival rate. Key secondary endpoints include pathological response, R0/1 resection rate, disease free survival , safety and QOL by EORTC QLQ-C30. This study is recruiting in The Sixth Affiliated Hospital of Sun Yat-sen University and registered as NCT02915965. Clinical trial information: NCT02915965.
T-ACT (WJOG7112G): A randomized phase II study of weekly paclitaxel ± trastuzumab in patients with HER2-positive advanced gastric or gastro-esophageal junction cancer refractory to trastuzumab combined with fluoropyrimidine and platinum.
Authors: Esaki Taito , Makiyama Akitaka , Kashiwada Tomomi , Hosokawa Ayumu , Kawada Junji , Moriwaki Toshikazu , Horie Yoshiki , Satake Hironaga , Shinozaki Katsunori , Ishida Hiroyasu , Tanioka Hiroaki , Tsukuda Hiroshi , Uchino Keita , Nishikawa Kazuhiro , Sukawa Yasutaka , Yamanaka Takeharu , Nakamura Shinichiro , Boku Narikazu , Hyodo Ichinosuke , Muro Kei 
Published: March 2017

TPS218 Background: Trastuzumab (Tmab) is a key drug for HER2 positive breast and gastric or gastro-esophageal junction (G/GEJ) cancer. While use of Tmab beyond progression (TBP) showed a benefit in HER2-positive metastatic breast cancer, clinical significance of TBP for HER2-positive G/GEJ cancer has not been clarified. Objective:This study compares the efficacy of paclitaxel (PTX) + Tmab with PTX alone in patients with unresectable or metastatic HER2-positive G/GEJ cancer who failed first-line chemotherapy with Tmab + fluoropyrimidine + platinum. Methods: Enrolled patients will be randomized to receive PTX (80 mg/m2, on day 1, 8 15, every 4 weeks) + Tmab (8 mg/kg loading dose and 6 mg/kg thereafter, on day 1, every 3 weeks) or PTX alone. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, time to treatment failure, response rate, disease control rate, safety, and translational biomarker research. A total of 69 events are required to achieve 80% power for one-sided log rank test with 10% significance level, expecting the median PFS of the PTX and the PTX + Tmab arms will be 3 and 5 months. In consideration of patient with censoring and dropout, the planned sample size is totally 90 patients. Major eligibility criteria are: HER2-positive advanced G/GEJ adenocarcinoma; refractory to first-line chemotherapy with fluoropyrimidine, platinum, and Tmab (at least three doses); within 6 weeks after last Tmab administration; no prior therapy with taxane or anti-HER2 drugs except Tmab; ECOG PS 0-2; adequate organ function; left ventricular ejection fraction ≥ 50%. Tumor tissue, blood serum, and circulating tumor DNA are collected before the study treatment for biomarker analyses to explore the predictive marker of the TBP strategy. As of September 2016, 89 patients were randomized. Clinical trial information: 000009297.
iMYC: Proof-of-concept study of ibrutinib in c-MYC and HER2 amplified oesophagogastric carcinoma.
Authors: Davidson Michael , Chong Irene Yu-Shing , Cunningham David , Aronson Lauren , Bryant Hanna , Begum Ruwaida , Swansbury John , Wotherspoon Andrew , Matthews Nik , To Ye Mong , Kalaitzaki Eleftheria , Yuan Lina , Watkins David J. , Starling Naureen , Rao Sheela , Chau Ian 
Published: March 2017

TPS221 Background: The MYC proto-oncogene is among the most frequently dysregulated genes in human cancer and is amplified in 10-30% of oesophagogastric (OG) cancers. Such genes which code for transcription factors are challenging to target directly with small molecule inhibitors or monoclonal antibodies. High-throughput siRNA screening of OG cell lines has found silencing of Bruton’s tyrosine kinase (BTK) to result in selective lethality in the presence of MYC amplification. Sensitivity to the orally available BTK inhibitor ibrutinib has been confirmed in-vitro in MYC, HER2 and co-amplified OG cancer cell lines (Chong, Ann Onc 2014), suggesting it may be a potentially effective therapeutic strategy in both MYC and HER2 amplified OG cancer. Methods: i MYC is an open label, phase II non-randomised study to assess the efficacy of ibrutinib in advanced pre-treated OG cancer. A novel FISH assay for tumour MYC amplification has been developed and pts are pre-screened for MYC and HER2 amplification. Eligibility includes metastatic or locally advanced inoperable OG cancer (SCC or adeno), MYC (ratio >2.5) and/or HER2 (ratio>2) amplification, progression after at least 1 prior line of chemotherapy +/- trastuzumab for advanced disease, PS 0-2 and no history of significant cardiovascular or bleeding disorders. Of the first 9 pts, at least 4 will demonstrate MYC amplification and remaining 5 will show either MYC or HER2 amplification, or co-amplification of both. Pts will be treated with ibrutinib monotherapy until progression or unacceptable toxicity. A Simon 2 stage design will be used for the primary endpoint of response rate, with interim analysis after 9 pts and maximum recruitment to 17 pts. Secondary endpoints include PFS, OS and exploratory translational and imaging biomarker analysis. Mandatory biopsy will be obtained at baseline and optional biopsies will be undertaken at day 10-14, week 8 and progression. The trial represents the first attempt at targeting MYC amplification via synthetic lethal gene interactions in OG cancer through the novel application of an existing anti-cancer drug. As of September 2016, 61 patients have consented for pre-screening, 19 completed MYC analysis and first patient has started treatment. Clinical trial information: 02884453.
KEYNOTE-240: Randomized phase III study of pembrolizumab versus best supportive care for second-line advanced hepatocellular carcinoma.
Authors: Finn Richard S. , Chan Stephen L. , Zhu Andrew X. , Knox Jennifer J. , Cheng Ann-Lii , Siegel Abby B. , Bautista Oliver , Watson Pat , Kudo Masatoshi 
Published: March 2017

TPS503 Background: There are no approved therapies for patients with hepatocellular carcinoma (HCC) after disease progression on sorafenib, or for patients with intolerance to sorafenib. HCC often arises in the background of chronic inflammation and is also associated with an immunosuppressed microenvironment, providing a strong rationale to evaluate immunotherapy in HCC. The randomized, double-blind, placebo-controlled phase 3 KEYNOTE-240 study (ClinicalTrials.gov, NCT02702401) was designed to compare the efficacy and safety of the anti–PD-1 antibody pembrolizumab + best supportive care (BSC) vs placebo + BSC in patients with previously treated advanced HCC. Methods: Eligibility criteria include age ≥18 years, confirmed diagnosis of Barcelona Clinic Liver Cancer (BCLC) stage C disease or BCLC stage B disease not amenable to or refractory to locoregional therapy, disease not amenable to a curative treatment approach (eg, transplantation, surgery, or ablation), documented progression after treatment with sorafenib or intolerance to sorafenib, Child-Pugh liver score A, and ECOG performance status 0-1. ~408 patients will be randomly assigned 2:1 to receive pembrolizumab 200 mg IV every 3 weeks (Q3W) + BSC or placebo Q3W + BSC for up to 35 cycles or until disease progression, unacceptable toxicity, patient withdrawal of consent, or investigator decision. Randomization will be stratified by geographic region, macrovascular invasion, and α-fetoprotein. BSC will be provided by the investigator per local treatment practices. Response will be assessed every 6 weeks per RECIST v1.1 by central imaging vendor review. Adverse events (AEs) will be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs) and graded per NCI CTCAE v4.0. Primary objectives are comparison of progression-free survival per RECIST v1.1 by central imaging vendor review and overall survival between treatment arms. Secondary objectives are comparison of objective response rate, duration of response, disease control rate, and time to progression per RECIST v1.1 by central imaging vendor review, and evaluation of safety and tolerability. Enrollment in KEYNOTE-240 is ongoing. Clinical trial information: NCT02702401.
A phase II multicenter study evaluating combination immunotherapy with pembrolizumab and peginterferon alfa-2b for advanced cholangiocarcinoma.
Authors: He Aiwu Ruth , Morse Michael , Iyer Renuka V. , Sohal Davendra , Wang Hongkun , Dorsch-Vogel Karen , Pishvaian Michael J. , Salem Mohamed E. , Smaglo Brandon George , Marshall John 
Published: March 2017

TPS507 Background: No effective therapy is available for patients (pts) with advanced cholangiocarcinoma (CC) after disease progression on first-line chemotherapy. In Phase I studies, pembrolizumab (pem) showed activity in pts with advanced CC. Interferon alpha-2b was shown to increase tumor immune infiltrates. In order to improve the response rate (RR) of pts with CC to pem, we propose to combine sylatron with pem in an open-label, single-arm, multicenter Phase II study. Methods: To be eligible for study, pts must have CC, manifesting as either intrahepatic, extrahepatic or gallbladder cancer that is unresectable, metastatic, and has either failed to respond to or demonstrated progression on frontline chemotherapy. Forty-four pts will be enrolled on study to receive SC sylatron (200 mg) weekly for 12 weeks, and IV pem (200mg) once every 3 weeks, starting on week 4 (at the same time as the 4th dose of sylatron), until pts experience disease progression or unacceptable toxicity, or withdraw consent. CT scans will be performed every 9 weeks. The primary endpoints are overall RR (ORR) and the safety and tolerability of combined pem and sylatron therapy. Secondary endpoints include OS, PFS, and ORR by irRECIST. An initial 3-week window will exist in which to evaluate the effect of sylatron alone (following prior chemotherapy) on the tumor microenvironment: one biopsy (biopsy 1) will be obtained before the start of sylatron therapy, and another (biopsy 2) after the third but before the fourth injection of sylatron (and the initiation of pem plus sylatron combination therapy). The effect of sylatron on the CC immune microenvironment will be studied by comparing biopsies 1 and 2. Immune microenvironment in pem + sylatron responders will be compared with non-responders. The study will assess whether the addition of sylatron improves the RR of pem from 17% to 35% in pts with advanced CC. Simon’s two-stage optimum design will be used to test the null hypothesis that P ≤ 0.17 vs. the alternative hypothesis that P ≥ 0.350. This study design provides 80% power (one-sided significance level of 0.05). The time-to-event endpoints (PFS, OS) will be estimated using Kaplan-Meier methodology.
Phase I/IB multicenter study of afatinib in combination with capecitabine in patients (pts) with refractory solid tumors and pancreatico-biliary cancers.
Authors: Chang Amy E. , Shahda Safi , Harris William Proctor , Cohen Stacey , Coveler Andrew L. , O'Neil Bert H. , Gadi Vijayakrishna K. , Hibbert Reina , Lee Hannah H , Younger Anne , McCormick Kinsey Ann , Pritchard Colin , Redman Mary Weber , Chiorean E. Gabriela 
Published: March 2017

TPS515 Background: The epidermal growth factor receptor (EGFR)/HER2 pathway is overactive in several solid tumors, including gastroesophageal, hepatic, colorectal, and pancreatico-biliary cancers. Afatinib is an irreversible inhibitor of the Erb family approved for metastatic non-small cell lung cancer with EGFR mutations. Afatinib downregulates thymidine synthase (TS) the intracellular target of fluoropyrimidine chemotherapy such as capecitabine. Treatment of colorectal cancer cell lines with cytotoxic drugs can up-regulate EGFR expression, and increase sensitivity to EGFR inhibition. Based on this preclinical rationale, and given that capecitabine is commonly used in refractory gastrointestinal cancers, we have developed a phase I/Ib trial to evaluate the safety and maximum tolerated dose (MTD) of afatinib with capecitabine in advanced solid tumors, and assess preliminary antitumor activity in pts with refractory pancreatico-biliary cancers at MTD. Methods: Eligible pts have metastatic solid tumors (phase I) or pancreatico-biliary cancers (phase Ib), ECOG PS 0-2 (PS 0-1 phase Ib), any number of prior therapies (phase I), or ≤ 2 prior therapies (phase Ib), no prior erlotinib (phase Ib), and have archived paraffin embedded tumor tissue, or ability to undergo tumor biopsy at baseline. Tumor tissue is analyzed with UW-OncoPlex, a multiplexed gene sequencing panel of 200+ cancer-related genes, to identify predictive biomarkers of benefit. The study design is standard “3+3”. Afatinib is administered orally (PO) daily (QD) in escalating doses of 20, 30 and 40 mg, with capecitabine at 1000 mg/m2 PO BID Days 1-14, in 21-day cycles (C). Dose limiting toxicity (DLT) is assessed in C1. Once the MTD is identified, the phase Ib expansion cohorts will enroll 15 pts each with refractory pancreatic and biliary cancers, with afatinib dosed at MTD and standard dose capecitabine. The study was activated in November 2015, and to date 4 pts were enrolled in cohort 1, 3 pts in cohort 2, and 2 pts in cohort 3. The phase I is ongoing and the phase Ib is expected to start enrollment in December 2016. Clinical trial information: NCT02451553.
5-fluorouracil, oxaliplatin and dasatinib (FOLFOX-D) for previously untreated metastatic pancreatic adenocarcinoma.
Authors: George Thomas J. , Dang Long H. , Daily Karen Colleen , Starr Jason Scott , Parekh Hiral D. , Ivey Alison Marguerite , Delitto Daniel , Allegra Carmen Joseph , Hughes Steven J. , Lu Xiaomin , McEwan Margaret A. , Cioffi Jessica L , Trevino Jose Gilberto 
Published: March 2017

TPS517 Background: Systemic chemotherapy for pancreatic adenocarcinoma improves survival and cancer related symptoms. Most targeted agents combined with gemcitabine have consistently failed to demonstrate clinical benefits. Src is overexpressed in pancreatic cancer and promotes an aggressive cancer phenotype. Dasatinib (D) is an oral multi-tyrosine kinase inhibitor (TKI) affecting tumor proliferation through inhibition of Src, Bcr-Abl, CKit and other pathways. Inhibition of Src is associated with biologic modifications favorably modifying the pancreatic cancer phenotype and has synergy with restoring inherent chemosensitivity. Src inhibition can also increase oxaliplatin activity and modulate Tcell responses. The addition of D to the well-established backbone of FOLFOX represents a multifaceted line of scientific investigation. Methods: This is a multicenter phase II trial to determine activity and toxicity of FOLFOX + D in previously untreated metastatic pancreatic adenocarcinoma. Eligible pts must have at least 1 measurable target lesion by RECIST, ECOG PS 0-2, normal QTc and adequate organ function. Pts received standard cycles of mFOLFOX6 repeated q14d with continuous D (150mg PO daily). Tumor assessments occur q8w. Endpoints included progression-free survival (primary; PFS), objective and biochemical response rates, clinical benefit rate, freedom from metastases, overall survival (OS), toxicity, and quality of life. Exploratory tissue, circulating tumor cell and serum analyses to identify predictors of response are planned, particularly in those demonstrating durable disease control or exceptional response. Sample size was based on a 50% improved median PFS from 4 (historical) to 6 months. NCT01652976. Results: Enrollment continues on this prospective phase II study with 38 of 42 evaluable patients. There are no unexpected toxicities noted thus far. Clinical trial information: NCT01652976. [Table: see text]