bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRICC-c: BIBF 1120 versus placebo in patients receiving oxaliplatin plus fluorouracil and leucovorin (mFOLFOX6) for advanced, chemorefractory metastatic colorectal cancer (mCRC)—A multicenter, randomized phase II trial in progress.
Authors: Berger Andreas , Ettrich Thomas , Marten Angela , Seufferlein Thomas 
Published: March 2020

TPS3636 Background: Colorectal cancer (CRC) is the second leading cause of cancer-related death in western countries. With advances in the treatment of metastatic CRC (mCRC) in the last decade using combination chemotherapy and bevacizumab, a monoclonal antibody against the vascular endothelial growth factor (VEGF), progression free survival (PFS) in first and second line setting was substantially improved. Tumour angiogenesis is also driven by other factors but VEGF including Platelet Derived Growth Factor (PDGF) and Fibroblast Growth Factor (FGF). BIBF1120 is a potent, orally available triple angiokinase inhibitor that blocks the receptor tyrosine kinase activity of human VEGFR1-3, FGFR1 and -3 and PDGFRα and -β. Thus, BIBF1120 could be an exciting addition to the treatment of patients with chemorefractory CRC. Methods: Randomized, double-blind, placebo-controlled, multicentre, phase II trial of BIBF1120 (orally, 200 mg, bid, d1-d14, Arm A) vs. placebo (Arm B) in patients receiving mFOLFOX6 (oxaliplatin, 85 mg/m2, fluorouracil, 400 mg/m2 bolus and 2400 mg/m2 over 46 h, leucovorin, 200 mg/m2) q14 d for patients (ECOG performance status 0-1) with chemorefractory mCRC who received one prior line of chemotherapy. Scheduled are 90 patients per treatment arm. Primary endpoint: PFS, Secondary endpoints: objective response, overall survival, duration of overall response, safety. Additionally there will be an explorative analysis of predictive biomarkers for BIBF1120. 4 of planned 180 patients have been enrolled. We expect the last patient out in June 2013. (Trial identifier: NCT01362361.)
Sequential first-line treatment for metastatic colorectal cancer with capecitabine, irinotecan, and bevacizumab: Capecitabine plus bevacizumab (Cape-Bev) versus capecitabine, irinotecan plus bevacizumab (CAPIRI-Bev): The AIO KRK 0110/ML22011 randomized, phase III trial.
Authors: Giessen Clemens Albrecht , Modest Dominik Paul , Stintzing Sebastian , Fischer von Weikersthal Ludwig , Vehling-Kaiser Ursula , Spaeth-Schwalbe Ernst , Freiberg-Richter Jens , Mayerle Julia , Bangerter Markus , Denzlinger Claudio , Sieber Markus , Teschendorf Christian , Peuser Bettina , Heinemann Volker 
Published: March 2020

TPS3639 Background: Several randomized trials have indicated that combination chemotherapy applied in metastatic colorectal cancer (mCRC) does not significantly improve overall survival when compared to the sequential use of cytotoxic agents (CAIRO, MRC Focus, FFCD 2000-05). The present study investigates the question in bevacizumab-based first-line treatment including escalation- and de-escalation strategies. Methods: The AIO KRK 0110/ML22011 trial (ClinicalTrials.gov NCT01249638) is a two-arm, multicenter, open-label randomized phase III trial comparing the efficacy and safety of Cape-Bev versus CAPIRI-Bev in the first-line treatment of metastatic colorectal cancer. Patients with unresectable metastatic colorectal cancer, ECOG PS 0-1, will be assigned in a 1:1 ratio to receive either capecitabine 1250 mg/m2 bid for 14d (d1-14) plus bevacizumab 7.5 mg/kg (d1) q3w (Arm A) or capecitabine 800 mg/m2 BID for 14d (d1-14), irinotecan 200 mg/m2 (d1) and bevacizumab 7.5 mg/kg (d1) q3w (Arm B). Patients included into this trial are required to consent to the analysis of tumor tissue and blood for translational investigations. In Arm A, treatment escalation from Cape-Bev to CAPIRI-Bev is recommended in case of progressive disease (PD). In Arm B, de-escalation from CAPIRI-Bev to Cape-Bev is possible after 6 months of treatment or in case of irinotecan-associated toxicity. Re-escalation to CAPIRI-Bev after PD is possible. The primary endpoint is time to failure of strategy (TFS). Secondary endpoints are ORR, OS, PFS, safety and quality of life. Conclusion: The AIO KRK 0110 trial is designed for patients with disseminated, but asymptomatic mCRC who are not potential candidates for surgical resection of metastasis. Two bevacizumab-based strategies are compared: one starting as single-agent chemotherapy (Cape-Bev) allowing escalation to CAPIRI-Bev and another starting with CAPIRI-Bev and allowing de-escalation to Cape-Bev and subsequent re-escalation if necessary. By January 2012, 79 of planned 516 patients have been enrolled.
A randomized, multicenter, double-blind, placebo (PBO)-controlled phase III study of paclitaxel (PTX) with or without ramucirumab (IMC-1121B; RAM) in patients (pts) with metastatic gastric adenocarcinoma, refractory to or progressive after first-line therapy with platinum (PLT) and fluoropyrimidine (FP).
Authors: Wilke Hansjochen , Cunningham David , Ohtsu Atsushi , Nuber Ulrike , Bruns Rolf , Schmitt-Bormann Beate 
Published: March 2020

TPS4139 Background: Vascular endothelial growth factor (VEGF) expression in gastric cancer (GC) is associated with more aggressive clinical disease. VEGF expression in resected GC is associated with tumor recurrence and shorter survival. Data from Phase 2 and 3 studies suggest that agents targeting the VEGF pathway improve the efficacy of some chemotherapy regimens in 1st- and 2nd-line treatment of patients with gastric or gastroesophageal carcinomas. RAM, a fully human monoclonal antibody, binds to the VEGF receptor-2 (VEGFR-2), potently blocks the binding of VEGF to VEGFR-2, inhibits VEGF-stimulated activation of VEGFR-2, and neutralizes VEGF-induced mitogenesis of human endothelial cells. Methods: Pts are randomized 1:1 to receive PTX + RAM or PTX + PBO until disease progression or intolerable toxicity (28-day cycle; RAM/PBO 8 mg/kg Days 1, 15; PTX 80 mg/m2 Days 1, 8, 15). Eligibility includes metastatic or locally advanced, unresectable gastric or gastroesophageal junction adenocarcinoma; prior first-line therapy with any PLT/FP doublet with or without anthracycline; progressive disease during or following first-line therapy; ECOG PS 0-1; bilirubin ≤ 1.5 × upper limit of normal (ULN), transaminases ≤ 3 × ULN for ALAT/ASAT if no liver metastases, < 5 × ULN if liver metastases; creatinine ≤ 1.5 × ULN; absolute neutrophil count ≥ 1.5 × 109/L, hemoglobin ≥ 9 g/dL; platelets ≥ 100 × 109/L. The primary endpoint is overall survival (OS). Secondary endpoints include progression-free survival, time to progression, best overall response, objective response rate, safety, patient-reported outcome measures, pharmacodynamics, immunogenicity, and pharmacokinetics. This study, powered at 90% to show an increase in OS (mdn: 7 m PTX + PBO, 9.33 m PTX + RAM) at a 1-sided 2.5% significance level, will randomize 663 pts. As of 18 January 2012, approximately 58% of planned pts were randomized. The IDMC reviewed this study 23 June and 01 December 2011 and recommended the study continue unmodified.
Lapatinib in combination with ECF/x in EGFR1 positive first-line metastatic gastric cancer (GC): A phase II randomized placebo controlled trial (EORTC 40071).
Authors: Moehler Markus Hermann , Schad Arno , Mauer Murielle E. , Praet Michel , Sapunar Francisco J. , Briggs Kathryn Jane , Lutz Manfred P. , Roth Arnaud 
Published: March 2020

TPS4140 Background: Survival of HER2+ metastatic GC is prolonged by trastuzumab when administered with CF/X (VanCutsem, ASCO 2009). Lapatinib inhibits both EGFR1 and HER2, is active in HER2+ GC lines, and has shown clinical activity in uncontrolled phase II GC trials. A phase III trial of lapatinib with X + oxaliplatin in HER2+ (FISH) GC is closed to recruitment. Additional unaddressed questions include the efficacy and safety of lapatinib with ECF/X (epirubicin + cisplatin + 5-FU or capecitabine (X), which is a preferred chemotherapy (CT) regimen in GC), and its activity in patients (pts) with discordant FISH or IHC HER2 status or EGFR1+. Methods: This is a phase II, randomized, double- blind, placebo controlled, multicenter trial sponsored by the EORTC. About 480 pts with adenocarcinoma of the stomach or esophagogastric junction not amenable to curative surgery and without prior palliative CT are screened centrally for HER2/EGFR1 by FISH and IHC. Patients are enrolled into one of two strata: 1) HER2 FISH- and IHC 2/3+, or 2) HER2 IHC 0/+ and EGFR1 FISH+ or IHC 2/3+. Pts HER2 FISH+/IHC 2/3+ and pts without HER2/EGFR1 by FISH/IHC will be excluded. 168 pts are anticipated to be randomized to lapatinib 1,250 mg cont. until progression or placebo, administered 6 cycles of ECF or ECX (72/96 in stratum 1/2, respectively).The primary endpoint is progression-free survival (PFS) in stratum 2 and 77 events are needed for 80% power to detect an increase in PFS from 4 to 6.5 months with lapatinib (HR=0.615, one-sided alpha 10%). Secondary endpoints include PFS, toxicity, response rate, overall survival, and correlation of HER2/EGFR1 status with response. Currently, half of all screened patients (19/38) have been randomized. So far, 8/38 (21%) pts were HER2+ according TOGA criteria. By FISH or IHC, 14/38 were EGFR1+, with 4/14 pts double HER2/EGFR+. Enrolment continues in 5 centers with about 4-10 patients per month. A safety cohort analysis will be performed in the first 15 pts receiving lapatinib. Conclusions: This is the first trial to analyze prospectively and separately the role of lapatinib combined with chemotherapy in EGFR1+ GC pts stratified by FISH/ IHC.
DOCTOR: A randomized phase II trial of preoperative cisplatin, 5-fluorouracil, and docetaxel with or without radiotherapy based on poor early response to standard chemotherapy for resectable adenocarcinoma of the esophagus and/or OG junction.
Authors: Barbour Andrew , Smithers Bernard Mark , Burmeister Bryan , Zalcberg John Raymond , Spry Nigel , Smith Garrett , Wilson Kate , Roff Kate , Yip Sonia , Walpole Euan Thomas ,   Australasian Gastro-Intestinal Trials Groups (AGITG)
Published: March 2020

TPS4145 Background: Surgery forms the mainstay of curative treatment for oesophageal and gastro-oesophageal junction adenocarcinoma (OAC). Preoperative chemotherapy (CTX) with or without concurrent radiotherapy (CRT) have resulted in modest improvements in outcome. Patients who demonstrate a histological response in the resected specimen following pre-operative therapy (CTX or CRT) have consistently better survival than non-responders. Recent data suggests that early metabolic response, assessed by FDG-PET scan performed 14+/-1 days after the start of CTX compared with a baseline PET scan, is predictive of a histological response and improved survival. Increasing the proportion of responders to pre-operative therapy remains one of the major challenges facing patients with localised OAC. Methods: 150 patients with resectable adenocarcinona of the oesophagus or GOJ will be registered and given 1 cycle of cisplatin and 5FU (CF). Patients will undergo a series of baseline tests including endoscopy, endoscopic ultrasound and 18FDG-PET. At Day 15 of the initial CF cycle the PET will be repeated. Patients with a PET response (≥ 35% reduction in SUVmax) to initial treatment will continue with CF as standard treatment prior to surgery. PET non-responders (< 35% reduction in SUVmax) will be randomized equally to receive either docetaxel, cisplatin and 5FU (DCF) or DCF plus radiatiotherapy. Following completion of the preoperative chemotherapy /chemoradiotherapy patients will have their cancer surgically removed. The primary end point is major histological response (<10% residual viable tumour) and secondary endpoints of progression-free and overall survival, toxicity, quality of life and feasibility of response-based therapy. Eligibility: T2 or greater tumours (by EUS or CT), or T1 tumours that are poorly differentiated, or T1 node positive, histologically proven invasive adenocarcinoma of the oesophagus or GOJ, technically resectable tumour which is sufficiently FDG avid on the initial PET staging scan. Status: Opened to accural 2009.
TACE 2: A randomized placebo-controlled, double-blinded, phase III trial evaluating sorafenib in combination with transarterial chemoembolisation (TACE) in patients with unresectable hepatocellular carcinoma (HCC).
Authors: Meyer Tim , Fox Richard , Bird Deborah , Watkinson Anthony , Hacking Nigel , Stocken Deborah , Johnson Philip James , Palmer Daniel H. 
Published: March 2020

TPS4150 Background: TACE is regarded as the standard of care for patients with intermediate stage HCC (BCLC B), while sorafenib (S) is the current standard for advanced disease (BCLC C). The combination of S with TACE for intermediate disease is rational since sorafenib inhibits the action of VEGF which may be induced by tumour hypoxia following TACE, and S also has direct anti-tumour effect. The combination has been shown to be safe in and active in phase I and II studies. Phase III trials are now required to determine whether TACE + S is superior to TACE alone in terms of survival. Methods: We are conducting a double blind multicentre trial to determine if the addition of S to TACE is superior to TACE alone. This is a UK NCRI trial sponsored by University College London (UCL) (EudraCT 2008-005073-36). Patients with intermediate stage HCC are randomised 1:1 to continuous S (400mg BD) or placebo (P). Key inclusion criteria include unresectable HCC confined to the liver, patent main portal vein, ECOG PS ≤1 and Child Pugh A liver score. After randomisation patients commence study drug and TACE is performed at 2-5 weeks using drug eluting beads loaded with 150mg doxorubicin (Biocompatibles UK Ltd) according to a standard protocol. Further TACE is performed at the discretion of the investigator based on radiological response and patient tolerance. The primary outcome measure is progression free survival and central, external, real time radiology review is required to confirm progression. Secondary outcome measures are overall survival, time to progression, toxicity, disease control, quality of life and number of TACE procedures performed in 12 months. The target recruitment is 412 in order to detect a hazard ratio of 0.72 using a 2-sided level of significance of α=0.05 with 85% power. The trial was reviewed by the IDMC after the presentation of the SPACE trial (Lencioni et al J Clin Oncol 30, 2012). The IDMC concurred with the conclusion of the SPACE investigators that the combination is tolerated and results required confirmation in a phase III trial. Thus recruitment into the TACE2 trial will continue as planned.
A randomized phase III trial comparing sorafenib plus best supportive care (BSC) versus BSC alone in Child-Pugh B patients (pts) with advanced hepatocellular carcinoma (HCC): The BOOST study.
Authors: Daniele Bruno , Di Maio Massimo , Gallo Ciro , Gasbarrini Antonio , Carteni Giacomo , Di Costanzo Giovan Giuseppe , Craxi Antonio , Cabibbo Giuseppe , Bolondi Luigi , Granito Alessandro , Missale Gabriele , Frassoldati Antonio , Angelico Mario , Roselli Mario , Daniele Gennaro , Perrone Francesco 
Published: March 2020

TPS4151 Background: The efficacy of sorafenib in pts with advanced HCC has been demonstrated in two randomized phase III trials (Llovet JM, NEJM 2008;359:378; Cheng AL, Lancet Oncol 2009;10:25), both restricted to pts with well-preserved liver function (Child-Pugh A). Child-Pugh B (CPB) pts, that represent a relevant proportion of pts with advanced HCC in clinical practice, were not eligible. Despite this limitation, the marketing authorization of sorafenib by the main regulatory agencies was not restricted to Child A pts. CPB pts are different in terms of prognosis, and are potentially different in terms of balance between treatment efficacy and toxicity. Large observational studies [Marrero JA, ASCO 2011 (abstr 4001)] are producing quite reassuring data about sorafenib tolerability in CPB pts, but the real efficacy of the drug in this setting remains substantially unknown, due to the lack of randomized trials. Methods: BOOST (B Child HCC patients – Optimization Of Sorafenib Treatment) is a randomized phase III trial comparing sorafenib + best supportive care (BSC) vs. BSC alone in CPB pts with advanced HCC. Pts are eligible if older than 18, with ECOG performance status 0-2. Pts assigned to experimental arm receive sorafenib 400 mg twice daily, with dose reductions and interruptions according to toxicity. Overall survival (OS) is the primary endpoint. In order to demonstrate a Hazard Ratio of death 0.70 in favor of sorafenib (2-month improvement in median OS, from 4.5 to 6.5 months), with 80% power and α 0.05, 320 pts have to be randomized, 160 per arm. The BOOST trial (ClinicalTrials.gov Identifier NCT01405573; Eudract number 2009-013870-42) is approved by the Ethical Committee of the National Cancer Institute, Napoli, Italy, as coordinating centre, and is currently under evaluation by several other Institutions. BOOST is a non-profit, academic trial. The trial has received a financial support by Italian Ministry of Health (FARM84SA2X), although the support is not enough to supply sorafenib to participating centers. BOOST is partially supported by AIRC (grant IG2009-9316). The study is open to all international Centers wishing to participate.
Phase IIb randomized trial of JX-594, a targeted multimechanistic oncolytic vaccinia virus, plus best supportive care (BSC) versus BSC alone in patients with advanced hepatocellular carcinoma who have failed sorafenib treatment (TRAVERSE).
Authors: Burke James M. , Breitbach Caroline , Patt Richard H. , Lencioni Riccardo , Homerin Michel , Limacher Jean-Marc , Lusky Monika , Hickman Theresa , Longpre Lara , Kirn David H. 
Published: March 2020

TPS4152 Background: JX-594 is a first-in-class targeted oncolytic poxvirus designed to selectively replicate in and destroy cancer cells with epidermal growth factor receptor (EGFR)/ ras pathway activation. Direct oncolysis plus GM-CSF expression stimulates tumor vascular disruption and anti-tumor immunity (Nature Rev Cancer 2009). JX-594 was well-tolerated in Phase 1 trials and was shown to replicate in metastatic tumors following intratumoral (IT) or intravenous (IV) administration (Lancet Oncol 2008 and Nature 2011). A randomized dose-finding Phase 2 trial has been completed with JX-594 in 30 patients with advanced HCC. Treatment with high-dose JX-594 was associated with prolonged survival vs low-dose JX-594 (median survival 14.1 mo vs 6.7 mo; Hazard Ratio 0.39, p=0.02) (AASLD Annual Meeting, 2011, LB1). Methods: TRAVERSE is a Phase 2b randomized, open-label, multi-center trial of JX-594 plus BSC versus BSC in patients with advanced HCC who have failed sorafenib treatment. Approximately 120 patients will be randomized 2:1 to experimental and control arm respectively. Randomization will be stratified by region (Asian vs non-Asian); sorafenib intolerant vs refractory; and presence vs absence of extra-hepatic disease. The primary objective is to determine overall survival in the 2 arms. Assuming a control median overall survival of 4.0 months and a target hazard ratio of 0.57 (corresponding to an experimental arm median survival of 7.0 months), 73 events (deaths) will provide 70% power at 1-sided alpha = 0.05 to detect a difference in overall survival between the treatment groups using a stratified logrank test. Patients randomized to JX-594 will receive a dose of 109 plaque forming units (pfu) IV on Day 1 followed by five IT treatments between Day 8 and Week 18. Main inclusion criteria are advanced HCC having failed sorafenib (intolerance or radiographic progression during or < 3 months following last sorafenib), Child-Pugh A-B7 (no ascites), acceptable hematologic function. Enrollment has begun on this study with clinical trial registry number of NCT01387555.
Phase II trial of cabazitaxel in patients with advanced or metastatic transitional cell carcinoma of the urothelial tract who have progressed within less than 12 months after cisplatin-based chemotherapy: A Spanish Oncology Genitourinary Group (SOGUG) study.
Authors: Arranz Arija Jose Angel , Climent Duran Miguel Angel , Font Pous Albert , Garcia Alonso Mirta , Diaz Enrique Gallardo , Garcia del Muro Xavier , Gonzalez del Alba Aranzazu , Lainez Milagro Nuria , Lázaro Quintela Martin , López-Brea Marta F. , Lopez Criado M Pilar , Luque Caro Raquel , Martin Lorente Cristina , Mendez Vidal Maria Jose , Pinto Marin Alvaro , Saez M.I. , Santander Lobera Carmen , Vazquez Estévez Sergio , Echaburu Juan Virizuela , Duran Ignacio ,   Spanish Oncology Genitourinary Group (SOGUG)
Published: March 2020

TPS4672 Background: Advanced transitional cell carcinoma of the urothelium (TCCU) on progression after previous cisplatin-based combination is generally an incurable disease. The appropriate management of these patients is still an unmet need. Many drugs have shown modest or no activity in previous phase 2 trials. Population heterogeneity in these studies emerges as one of the key determinants that could explain the variable outcomes. Recently, in a phase III study in this setting, prognostic factors (PF) for overall survival were identified (Bellmunt J et al, JCO 2010). Taxanes are active drugs in 2nd-line metastatic TCCU. Cabazitaxel (C) is a semi-synthetic taxane that is a poor substrate for the multidrug resistance system. C could be a valid alternative in this patient population. Methods: This is an open label phase II study of C in patients (pts) with advanced or metastatic TCCU who have progressed within 12 months after receiving a 1st-line platinum based chemotherapy. There are three treatment arms as patients will be assigned to one of three groups previously defined based on the presence of 0, 1 or 2-3 PFs as defined by Bellmunt et al. The activity of C will be assessed separately in each group and overall. The primary endpoint is response rate (RR) evaluated according to RECIST 1.1, a maximum of 35 pts are needed in each subgroup (maximum number of pts required: 105). Secondary objectives are RR in the whole population, toxicity, progression-free survival and overall survival. In addition, an external validation of the prognostic model proposed by Bellmunt will be conducted, as well as a pharmacogenomic study in order to better define the toxicity profile of the drug and the potential responders.