bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.