bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized, double-blind, placebo-controlled, multicenter, multinational, phase II trial of L-BLP25 in patients with colorectal carcinoma following R0/R1 hepatic metastasectomy.
Authors: Schimanski Carl Christoph , Moehler Markus Hermann , Lang Hauke , Schoen Michael , Smith-Machnow Victoria , Kanzler Stephan , Hegewisch-Becker Susanna , Doerfel Steffen , Seehofer Daniel , Bechstein Wolf , Heike Michael , Overkamp Friedrich , Kullmann Frank , Voehringer Matthias , Heinemann Volker , von Wichert Goetz , Kasper Stefan , Greil Richard , Samonigg Hellmut , Galle Peter Robert 
Published: March 2020

TPS3641^ Background: Approximately 15-20% of patients diagnosed with colorectal cancer (crc) develop metastatic disease. Surgical resection remains the only potentially curative treatment. 5-year survival following R0-resection of liver metastases lies ~28 -39%. Recurrence occurs in ~70% of pts. Adjuvant chemotherapy has not significantly improved clinical outcomes. The primary objective of the LICC trial (L-BLP25 in Colorectal Cancer) is to analyze whether L-BLP25, an active cancer immunotherapy, extends recurrence-free survival (RFS) time over placebo in colorectal cancer pts following R0/R1 resection of hepatic metastases. L-BLP25 targets MUC1 glycoprotein, which is highly expressed in hepatic metastases from crc. In a phase IIB trial, L-BLP25 showed acceptable tolerability and a trend toward longer survival in pts with stage IIIB NSCLC. Methods: This is a multinational, phase II, multicenter, randomized, double-blind, placebo-controlled trial with a sample size of 159 pts from 20 centers in 3 countries. Pts must have stage IV cr adenocarcinoma limited to liver metastases. Following complete resection of the primary tumor and all syn-/metachronous metastases, eligible pts are randomized 2:1 to receive either L-BLP25 or placebo. Those allocated to L-BLP25 receive a single dose of 300 mg/m2 cyclophosphamide (CP) 3 days before first L-BLP25 dose, then primary treatment with sc L-BLP25 930 μg once weekly for 8 weeks, followed by maintenance doses at 6-week (years 1 and 2) and 12-week (year 3) intervals until recurrence. In the control arm, CP is replaced by saline solution and L-BLP25 by placebo. Primary endpoint: RFS time. Secondary endpoints: OS time, safety status, tolerability, RFS/OS in MUC-1 positive cancers. Exploratory immune response analyses are planned. First recruitment was of Q3 2011. To date, 8 of 20 centers are initiated and 4 pts recruited. Completion of recruitment is scheduled for Q3 2013. Primary endpoint will be assessed in Q3 2016: Follow-up will end Q3 2017. No interim analysis is planned. Design and implementation of this vaccination study in colorectal cancer is feasible. No major issues identified during setup of the study.
FOLFIRI plus 5 mg/kg of bevacizumab versus 10 mg/kg as second-line therapy in patients with metastatic colorectal cancer who have failed first-line bevacizumab plus oxaliplatin-based therapy: A randomized phase III study (EAGLE Study).
Authors: Nakamura Masato , Mishima Hideyuki , Iwamoto Shigeyoshi , Takahashi Takao , Tamagawa Hiroshi , Munemoto Yoshinori , Hata Taishi , Denda Tadamichi , Morita Yoshitaka , Inukai Michio , Murata Akihiko , Kunieda Katsuyuki , Nagata Naoki , Kurachi Yoshitaka , Oshiro Takashi , Ina Kenji , Miyamoto Yuji , Shimoyama Tatsu , Oba Koji , Sakamoto Junichi 
Published: March 2020

TPS3642 Background: There has been much controversy about continuation of bevacizumab (BV) with a second-line regimen after progression on a BV-containing first-line regimen. Recently, it was announced that a phase III study (AIO 0504 / ML 18147) met its primary endpoint of overall survival. It means BV-based regimen (5 mg/kg) extends survival when continued beyond initial treatment in patients with metastatic colorectal cancer(mCRC). The verified data from a randomized phase III study (E3200) indicates that BV at 10 mg/kg in the second-line setting followed by BV-naive treatment extends survival. The dose of BV 5 mg/kg could be lower than the recommended dose in the second-line CRC treatment. Thus we planned this second line phase III study (EAGLE study) to evaluate the appropriate dose of BV (5 or 10 mg/kg) with FOLFIRI in patients with mCRC who have failed BV plus oxaliplatin-based first line regimen. Methods: EAGLE is a multicenter randomized phase III study of FOLFIRI plus BV 5 mg/kg versus 10 mg/kg in mCRC who have failed BV plus oxaliplatin-based first line regimen (UMIN000002557).The primary endpoint is PFS. The secondary endpoints are the toxicity, response rate, time to treatment failure, OS. Eligible patients were older than 20 years of age, had histologically proved CRC, ECOG performance status 0 or 1, adequate organ function, progression or difficult to continue after BV plus oxaliplatin-based first line regimen, more than four times administration of BV and oxaliplatin in the first-line. Patients were randomized 1:1 to FOLFIRI with BV 5mg/kg or 10 mg/kg.The planned sample size was 370 patients to detect 30% risk reduction (median PFS assumed to be 5.0 months in arm A, 7.0 months in arm B) with 90% power assuming a two-sided significance level of 0.05, an accrual time of 2.5 years and a follow-up time of 1 year. Between September 2009 to January 2012, 387 patients were enrolled at 100 sites in Japan. This phase III study will answer the question of the appropriate dose of BV after progression on a BV-containing first-line regimen.
Dasatinib combined with gemcitabine (Gem) in patients (pts) with locally advanced pancreatic adenocarcinoma (PaCa): Design of CA180-375, a placebo-controlled, randomized, double-blind phase II trial.
Authors: Evans T.R. Jeffry , Van Cutsem Eric , Moore Malcolm J. , Purvis Joseph D. , Strauss Lewis C. , Rock Edwin P. , Lee Jennifer , Lin Chihche , Rosemurgy Alexander , Arena Francis P. , Gara Michelle , Armstrong Elizabeth , O'Dwyer Peter J. 
Published: March 2020

TPS4134 Background: Dasatinib, a potent oral BCR-ABL and SRC family kinase (SFK) inhibitor, is approved for first- and second-line therapy of Philadelphia chromosome-positive chronic phase chronic myeloid leukemia (CML) in pts with newly diagnosed CML or CML resistant/intolerant to prior therapy. SRC expression and activity is upregulated in PaCa and correlates with reduced survival in resected high-grade PaCa (Morton, Gastroenterology 2010) and resistance to Gem, a PaCa standard of care (Duxbury, J Am Coll Surg 2004). In preclinical PaCa studies, inhibition of SFKs with dasatinib reduces tumor cell proliferation, migration, and invasion; increases apoptosis; sensitizes cells to Gem; and inhibits development of metastases in vivo either alone or in combination with Gem (Duxbury, Clin Cancer Res 2004; Duxbury, J Am Coll Surg 2004; Nagaraj, Mol Cancer Ther 2010; Morton, op cit). Phase I clinical studies of dasatinib and Gem therapy in PaCa have demonstrated feasibility and suggested efficacy of the combination (Uronis, ASCO 2009, abstract e15506). Methods: This double-blind phase II study tests whether addition of dasatinib to Gem is tolerable and improves efficacy in pts with histologically/cytologically confirmed unresectable locally advanced nonmetastatic PaCa. Eligible pts, aged ≥18 years with Eastern Cooperative Oncology Group performance status ≤1 and adequate organ function, are randomized 1:1 to Gem 1000 mg/m2 IV once weekly (Weeks 1–3 of a 4-week cycle) plus either dasatinib 100 mg once daily or matched placebo. Pts are treated until progression, unacceptable toxicity, withdrawal of consent, or study termination. The primary endpoint is OS, and secondary endpoints are progression-free survival and safety. Exploratory endpoints include freedom from distant metastases, measures of pain and fatigue, overall response rate, and carbohydrate antigen 19-9. Final study analysis will be conducted after 135 deaths; all pts will be followed for survival. To date, 23/200 pts have enrolled; estimated primary completion date is March 2013. ClinicalTrials.gov identifier: NCT01395017.
TOPGEAR: An international randomized phase III trial of preoperative chemoradiotherapy versus preoperative chemotherapy for resectable gastric cancer (AGITG/TROG/EORTC/NCIC CTG).
Authors: Leong Trevor , Smithers Mark , Michael Michael , Gebski Val , Boussioutas Alex , Miller Danielle , Zalcberg John Raymond , Wong Rebecca , Haustermans Karin 
Published: March 2020

TPS4141 Background: Optimal management of patients with resectable gastric cancer remains unknown. Since the INT0116 and MAGIC trials, there are 2 standards of care for adjuvant therapy: postoperative chemoradiotherapy (CRT) and perioperative ECF chemotherapy. The important question arising from these studies is whether CRT is superior to chemotherapy alone as adjuvant therapy. This randomized phase II/III trial will compare CRT to chemotherapy alone in the preoperative setting. Methods: Patients with resectable adenocarcinoma of the stomach or gastroesophageal junction will be randomized to receive either preoperative chemotherapy alone (ECFx3 as per MAGIC regimen) or preoperative CRT (ECFx2 followed by 45Gy of radiation with concurrent 5-FU). Following surgery, both groups will receive 3 further cycles of ECF. The trial is being conducted in two Parts; Part I (phase II component) will recruit 120 patients with the aim of demonstrating sufficient efficacy and safety of preoperative CRT, as well as trial feasibility. Part II (phase III component) will recruit a further 632 patients to provide a total of 752. The primary endpoint for Part I is pathological complete response rate, and for Part 2 it is overall survival. The trial includes formal quality of life and biological sub-studies. In addition, the trial incorporates a rigorous quality assurance program that includes real time central review of radiotherapy plans and central review of surgical technique. Current status: This study is an international, intergroup trial led by the Australasian Gastro-Intestinal Trials Group (AGITG), in collaboration with the Trans-Tasman Radiation Oncology Group (TROG), European Organisation for Research and Treatment of Cancer (EORTC) and the NCIC Clinical Trials Group. To date, 36 patients have been recruited from 20 sites in Australia and New Zealand; European and Canadian sites will commence recruitment in 2012.
Design of a phase II randomized, open-label trial of DN24-02, an autologous cellular immunotherapy targeting HER2/neu, in patients with surgically resected urothelial cancer at high risk of recurrence.
Authors: Bajorin Dean F. , Sharma Padmanee , Sims Robert Brownell , Sandler Andrew , Lerner Seth P. 
Published: March 2020

TPS4673 Background: Despite surgical resection and the use of (neo)adjuvant chemotherapy, up to 50% of patients with invasive urothelial carcinoma will have disease recurrence and eventually die of metastatic disease. New approaches are needed for these patients. Approximately 50% of patients with high-risk pathologic features have evidence of HER2 expression in the primary tumor or involved lymph nodes. DN24-02 is an autologous cellular immunotherapy targeting HER2, which is based on Dendreon’s Antigen Delivery Cassette technology – the same platform used for sipuleucel-T (an FDA-approved treatment for asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer). Each dose of DN24-02 is manufactured by culture of peripheral blood mononuclear cells obtained by leukapheresis with a recombinant antigen that comprises components of the intra- and extracellular domains of the HER2 antigen linked to GM-CSF. A product similar to DN24-02 has shown evidence of safety and immune response in phase I studies. Objectives: The primary objective is to determine whether DN24-02, given as adjuvant therapy following surgical resection, can prolong survival compared to standard of care (SOC). Secondary objectives are to evaluate disease-free survival, safety, and immune responses to DN24-02. Methods: Eligible patients will have undergone surgical resection of a primary urothelial cancer, with either ≥pT2 or pN+ staging, and HER2 expression ≥1+ by IHC based on pathologic review. Approximately 180 patients will be randomized (1:1) to receive three IV infusions of DN24-02 as adjuvant therapy approximately every 2 weeks, or SOC. Stratification will include 1) neoadjuvant chemotherapy vs surgery alone; and 2) positive (pN+) vs negative lymph node involvement (pN0). Other adjuvant chemotherapy will not be allowed. Patients can be treated per SOC if there is disease recurrence. Patients will be monitored for evidence of recurrence by imaging, and followed for survival. Cellular and serological immune responses will be assessed at baseline and post-DN24-02 therapy.
Neoadjuvant therapy preceding cytoreductive nephrectomy to develop individualized first-line therapy with everolimus for advanced renal cell carcinoma (RCC).
Authors: Sonpavde Guru , Amiel Gilad , Margulis Vitaly , Link Richard E , Lerner Seth P. , Raj Ganesh , Mayer Wesley A , Palapattu Ganesh S. , Lotan Yair , Sagalowsky Arthur I. , Higgins Linda C , Tello Sebrina A , Pavia-Jimenez Andrea , VonMerveldt Dendra , Brugarolas James 
Published: March 2020

TPS4678 Background: Everolimus (E), an orally administered mTOR inhibitor, is the conventional agent for progressive disease following vascular endothelial growth factor (VEGF) inhibitors for advanced RCC. Given the excellent tolerability and convenient oral administration, a rationale may be made to develop E as first-line therapy for selected patients. The period between diagnosis and cytoreductive nephrectomy (CN) may be utilized for brief therapy to capture biologic activity in tumor tissue and facilitate individualized systemic therapy. The agent may be resumed following CN and continued until progression. Pharmacodynamic (PD) alterations from baseline to CN tumor tissue may predict progression-free survival (PFS). We hypothesized that the application of this paradigm to E may enable the employment of first-line E in patients predicted to optimally benefit. Methods: This is a 27-patient phase II trial being conducted at the Baylor College of Medicine and University of Texas Southwestern, and 5 patients have been enrolled currently. Patients with ≥3 poor risk factors or those who refuse or are ineligible for VEGF inhibitors and have untreated metastatic RCC are eligible. Adequate hematologic, renal and hepatic function is required. The primary endpoint is PFS and secondary endpoints are response, survival and toxicities. Exploratory endpoints are tumor tissue, peripheral blood mononuclear cell (PBMC) and plasma PD studies and pharmacokinetic (PK) studies, and their association with PFS. PD studies include DNA, mRNA, protein and miRNA studies to evaluate the mTORC1 among other pathways. Patients initially undergo 4 core biopsies of the primary renal mass for fresh frozen tumor. Patients then receive E 10 mg orally once daily for 3-5 weeks. CN is performed within 24-48 hours after the last dose of E. At the time of CN and before separation from the vascular supply, 3 core biopsies are performed. E is resumed 2-4 weeks after CN and continued until progression or intolerable toxicities. Clinical and laboratory assessments are performed every 4-5 weeks, and imaging is performed every 8 weeks. A progressing metastatic site will be biopsied (4 core biopsies).
EVERSUN: A phase II trial of everolimus alternating with sunitinib as first-line therapy for advanced renal cell carcinoma (RCC) (ANZUP trial 0901).
Authors: Davis Ian D. , Gebski Val , Chatfield Mark D. , Grimison Peter S. , Kannourakis George , Boland Amy L , Thompson Jennifer , Stockler Martin R. ,   Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Published: March 2020

TPS4681 Background: Treatment of RCC has improved due to better understanding of its biology. New targeted therapies have improved time to progression and overall survival but the optimal sequencing of agents is unknown. Currently drugs are given sequentially, usually starting with sunitinib and often followed by an mTOR inhibitor or another VEGFR-targeted therapy, but resistance to both drugs eventually occurs probably due to host adaptive responses. We hypothesize that resistance might be delayed by planned alternation of treatments. Methods: EVERSUN is a single-arm, two-stage, multicenter, phase II clinical trial aiming to determine the activity and safety of an alternating regimen of two therapies with different targets (sunitinib and everolimus) in patients with advanced RCC. Key eligibility criteria: RCC with a clear cell component; metastatic or locally advanced disease not suitable for resection; ECOG performance status 0-1; low or intermediate MSKCC prognostic score. The primary endpoint is the status of being alive and progression-free (RECIST 1.1) 6 months after registration. Target accrual of 55 subjects gives 95% power and 95% confidence to distinguish between 6-month progression free survival rates of 64% or lower vs 84% or higher using a Simon 2-stage minimax design. The criteria for further evaluation come from the pivotal trial of single agent sunitinib as first line therapy for RCC, in which the 6-month progression free survival rate was 74%. Trial treatment is administered in 12-week (wk) cycles consisting of 4 wks of sunitinib (50 mg daily) followed by 2 wks rest, followed by 5 wks of everolimus (10 mg daily) followed by 1 wk rest. Disease progression is interpreted as failure of the most recent drug taken. Participants who stop one drug because of toxicity or disease progression, on or before the 6 month assessment, will continue the other drug until subsequent progression or prohibitive toxicity on the second drug. EVERSUN is an ANZUP Cancer Trials Group Ltd. trial coordinated by the NHMRC Clinical Trials Centre. Accrual commenced in September 2010 with 38/55 participants recruited as of the 31-Jan-12 from 17 Australian sites (ACTRN12609000643279).
A phase II biomarker assessment of tivozanib in oncology (BATON) trial in patients (pts) with advanced renal cell carcinoma (RCC).
Authors: Hutson Thomas E. , Rathmell Kimryn , Hudes Gary R. , Kabbinavar Fairooz , Vogelzang Nicholas J. , Knox Jennifer J. , Cowey C. Lance , Cho Daniel C. , Choueiri Toni K. 
Published: March 2020

TPS4686 Background: Tivozanib is an oral, potent, and selective tyrosine kinase inhibitor targeting all three vascular endothelial growth factor (VEGF) receptors; it showed efficacy and tolerability in a Phase II trial in pts with advanced RCC (Nosov et al. JCO 2011;29[18S]:4550). Preclinical studies have identified a 42-gene tivozanib resistance signature (Jie et al. EORTC-NCI-AACR 2010; abstract 608) that may be predictive of tivozanib sensitivity. This study (NCT01297244) is designed to evaluate these potential biomarkers for tivozanib activity in pts with advanced RCC. Methods: Pts with advanced RCC (stratified as clear cell or non-clear cell) who underwent nephrectomy and received ≤1 prior systemic treatment (no prior VEGF- or mammalian target of rapamycin–targeted therapy) entered this open-label, single-arm study conducted in the United States and Canada beginning January 2011. Pts receive tivozanib 1.5 mg/d orally (3 weeks on, 1 week off schedule). Primary objectives include correlation of biomarkers in blood (e.g. VEGF, hepatocyte growth factor [HGF]) and tumor tissue (e.g. CD68, hypoxia-induced factor, VEGF, HGF, and gene expression profiles) with clinical activity and/or treatment-related toxicity, and 6-month progression-free survival (PFS) rate. Secondary objectives include overall response rate (ORR), PFS, safety and tolerability, and pharmacokinetics. Contingency table methods will be used for biomarker correlation with ORR, and Cox proportional-hazards regression for correlation with PFS. Sample size (100 pts) is estimated based on clinical considerations and the precision with which 6-month PFS can be estimated. Biomarkers were defined at study outset; the requirement of prior nephrectomy ensured availability of primary tumors as controls for correlative analysis. As of January 2012, the study completed enrollment of 100 pts, demonstrating a large number of pts can be enrolled to a biomarker study with well-defined candidate genes and critical inclusion criteria to facilitate compliance. Tivozanib biomarkers evaluated in this study, along with those evaluated in other solid tumors, may play an important role in optimizing patient selection.
Comparison of two doses of cabazitaxel plus prednisone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with a docetaxel (D)-containing regimen.
Authors: Eisenberger Mario A. , Hardy-Bessard Anne-Claire , Mourey Loic , Mainwaring Paul N. , Ford Daniel , Shapiro Jeremy David , Carles Joan , Ng Siobhan , Gil Thierry , Alekseev Boris , Ivanov Sergey , Facchini Thomas , Legouffe Eric , Apolikhin Oleg , Pandha Hardev S. , Beeker Aart , Karyakin Oleg , Zhang Wendy , Chadjaa Mustapha , De Bono Johann Sebastian 
Published: March 2020

TPS4692^ Background: The phase III TROPIC study (NCT00417079) reported a significant improvement in overall survival (OS) for cabazitaxel (Cbz) + prednisone (P;CbzP) (25 mg/m2 IV Q3W/10 mg PO QD) vs mitoxantrone (M) + P (MP) (median OS 15.1 vs 12.7 mos; HR 0.70; P < 0.0001) in pts with mCRPC (also known as hormone-refractory prostate cancer) previously treated with a D-containing regimen. CbzP is approved by the FDA, EMA and other health authorities for the treatment of pts with mCRPC that has progressed after a D-containing regimen. Cbz toxicity is consistent with other taxanes; compared with M, more hematologic toxicities are reported (primarily Grade 3–4 neutropenia). Phase I/II studies identified 20 and 25 mg/m2 as recommended doses; 25 mg/m2 was selected for the phase III TROPIC study. As pooled data show Grade 3–4 neutropenia incidence is lower with Cbz < 25 mg/m2 (61%) vs ≥ 25 mg/m2 (74%), it is of interest to assess if reducing the Cbz approved dose in mCRPC lessens hematologic toxicity and is non-inferior in terms of efficacy. Methods: PROSELICA (NCT01308580) is a randomized, open-label, multinational, phase III study comparing 20 mg/m2 and 25 mg/m2 Cbz for efficacy and tolerability. Pts with a life expectancy > 6 mos, ECOG PS ≤ 2, histologically/cytologically confirmed metastatic prostate adenocarcinoma resistant to hormone therapy and previously treated with a D-containing regimen are eligible. Pts are randomized 1:1 to receive Cbz 20 mg/m² or 25 mg/m² IV Q3W + P 10 mg PO QD, treated until disease progression, unacceptable toxicity or withdrawal of consent (max 10 cycles), and stratified according to ECOG PS, measurable disease (yes/no) and region. The primary endpoint is OS (non-inferiority design). Secondary endpoints include safety, progression-free survival (PCWG2 criteria), PSA and pain progression and response, tumor response in pts with measurable disease and health-related quality of life. Cbz PK and pharmacogenomics will be assessed in pt subgroups. Planned enrollment is 1,200 pts. Study start was in May 2011; as of Jan 2012, 270 pts had been enrolled. The first DMC meeting recommended continuing the study without change.