bluuebunny/crossref_metadata_2025_split huggingface dataset:
ICE CREAM: Irinotecan cetuximab evaluation and the cetuximab response evaluation among patients with G13D mutation.
Authors: Segelov Eva , Wilson Kate , Gebski Val , Waring Paul Michael , Tabernero Josep , Wasan Harpreet , Ciardiello Fortunato , Desai Jayesh , Underhill Craig , Karapetis Christos Stelios , Khasraw Mustafa , Nott Louise M. , Joubert Warren Lance , Pavlakis Nick , Van Hazel Guy , Chantrill Lorraine A. , Price Timothy Jay , Jefford Michael , Haydon Andrew Mark , Shapiro Jeremy David 
Published: March 2020

TPS3649 Background: Patients with metastatic colorectal cancer (mCRC) whose disease has progressed despite oxaliplatin and irinotecan containing regimens may benefit from the use of EGFR-inhibiting monoclonal antibodies if the tumor contains no mutations in the KRASgene (i.e. WT). However, it is unknown whether antibodies used in this setting, such as cetuximab, are more efficacious alone or in combination with irinotecan, as suggested by the BOND study which did not select for KRASstatus. This international trial will also evaluate prospectively the activity of cetuximab in the subgroup of patients with mCRC with a specific KRASmutation in codon G13D. In selected retrospective analyses, tumors bearing this mutation appear to derive similar response from cetuximab as WT. Trials involving small molecular subsets (in this case approx. 5% of patients with mCRC, or 18% of patients with KRAS mutations) will provide framework for future collaborations. Methods: This randomised phase II study of cetuximab +/- irinotecan will recruit patients with metastatic colorectal cancer (mCRC) with either KRAS WT (n=50) or G13D mutation (n=50) over 2 years from sites in Australia (12), and three international sites (G13D mutations only): Spain (1), England (1), and Italy (1). The trial will prospectively select the KRAS WT arm for the “quadruple WT" genotype (no mutations also in BRAF, NRAS, PIK3CA exon20). Primary objective is 6 month progression free survival. Secondary objectives are response rate, overall survival, quality of life, and translational research including markers that may predict response such as amphiregulin and epiregulin determined by immunohistochemistry. Eligibility: Patients with histologically confirmed CRC with either “quadruple WT" genotype or KRAS G13D mutation; unresectable metastatic disease; measurable or evaluable disease; ECOG 0-2; life expectancy at least 12 weeks, and disease progression, or intolerance of thymidylate synthase inhibitor and irinotecan and oxaliplatin containing regimens. Status: Opened to accrual November 2012, at 31 Jan 2013 3/100 patients have been enrolled, all with G13D mutations. Clinical trial information: ACTRN12612000901808.
Phase II clinical trial of biomarker-directed therapy for localized pancreatic cancer.
Authors: Tsai Susan , Ritch Paul S. , Erickson Beth , Kelly Tracy R. , Quebbeman Edward , Evans Douglas B. , Mackinnon Alexander C. , Christians Kathleen K. 
Published: March 2020

TPS4147 Background: Several candidate biomarkers exist for the common chemotherapeutic agents used to treat pancreatic cancer (PC) (Table). The predictive value of these markers in the treatment of PC has not been established. This is the first prospective clinical trial utilizing biomarker-directed therapy for localized pancreatic cancer. Methods: Patients with localized pancreatic cancer undergo endoscopic ultrasound-guided fine needle aspiration (FNA) for confirmation of diagnosis and immunohistochemical profiling . Six biomarkers (STREET profile) were selected based on their relevance to accepted pancreatic chemotherapy regimens (table). The treatment algorithm selected for each individual patient is based on the clinical stage of resectability (resectable/borderline resectable) and the STREET profile results. Neoadjuvant therapy is followed by restaging (CT and serum Ca19-9) and in the absence of disease progression, patients undergo surgery. Post-surgical (adjuvant) therapy is determined by the STREET profile of the resected specimen. The primary endpoint is an increase in the rate of surgical resection 20% compared with historical controls treated with best available neoadjuvant therapy which was not biomarker-directed. Secondary endpoints include assessment of overall and progression-free survival, comparative STREET profiling of pre- and post-treatment specimens, and changes in radiographic response. Eligbility Criteria: Patients with resectable or borderline resectable pancreatic cancer undergo endoscopic ultrasound-guided fine needle aspiration (FNA) for confirmation of diagnosis and immunohistochemical profiling. Enrollment: 26 of planned 100 patients have been enrolled. Clinical trial information: NCT01726582. [Table: see text]
Next study (JCOG1109): A three-arm randomized phase III study comparing preoperative CDDP+5-FU(CF) versus docetaxel+CF versus CF-radiation followed by esophagectomy with D2-3 lymphadenectomy for locally advanced esophageal squamous cell cancer.
Authors: Kato Ken , Igaki Hiroyasu , Ito Yoshinori , Mizusawa Junki , Tsubosa Yasuhiro , Nakagawa Satoru , Daiko Hiroyuki , Hironaka Shuichi , Udagawa Harushi , Hayashi Kazuhiko , Nozaki Isao , Yano Masahiko , Kimura Yusuke , Matsushita Hisayuki , Abe Tetsuya , Okabe Hiroshi , Nakamura Kenichi , Fukuda Haruhiko , Hirao Motohiro , Kitagawa Yuko 
Published: March 2020

TPS4152 Background: Based on the results of JCOG9907, preoperative cisplatin plus 5- fluorouracil (CF) followed by esophagectomy with D2-3 lymphadenectomy has become standard care for advanced esophageal cancer in Japan, while the standard therapy in Western countries is preoperative chemoradiotherapy. A new clinical question has thus arisen of whether CF plus docetaxel (DCF) or CF plus radiotherapy (CF-RT) shows a survival benefit over preoperative CF even with intensive surgery. Methods: Eligibility criteria include histologically proven thoracic esophageal squamous cell carcinoma with stage IB/II/III (excluding T4) based on the 7th UICC-TNM, age 20 to 75, and performance status 0 to 1. No prior chemotherapy, radiotherapy, or hormonal therapy is allowed. Adequate organ function and written informed consent are required. Patients are randomized into any of the following three arms by a minimization method balancing the arms in terms of institution and tumor depth (T1–2 versus T3). Patients in arm A (CF) receive two courses of cisplatin at 80 mg/m2 on day 1 and fluorouracil at 800 mg/m2 on days 1–5, repeated every three weeks. Patients in arm B (DCF) receive three courses of docetaxel at 70 mg/m2, cisplatin at 70 mg/m2 on day 1, and fluorouracil at 750 mg/m2 on days 1–5, repeated every three weeks. Patients in arm C (CF-RT) receive two courses of cisplatin at 75 mg/m2 on day 1 and fluorouracil at 1000 mg/m2 on days 1–4, repeated every four weeks concurrently with radiotherapy at 41.4Gy/23fr. This trial is designed to demonstrate the superiority of preoperative DCF and/or CF-RT over CF in terms of overall survival. We assumed three-year survival with preoperative CF to be 63% and expected a 10% increase in three-year survival for DCF and CF-RT. The sample size was calculated as a total of 501 patients (167 patients per arm) with a study-wise one-sided alpha level of 5%, power of 70% for each pair comparison, an accrual period of 6.25 years, and a follow-up period of three years. This trial was registered as UMIN000009482 and started in December 2012. Clinical trial information: UMIN000009482.
POWER: An open-label, randomized phase III trial of cisplatin and 5-FU with or without panitumumab (P) for patients (pts) with nonresectable, advanced, or metastatic esophageal squamous cell cancer (ESCC).
Authors: Moehler Markus Hermann , Ringshausen Ingo , Hofheinz Ralf , Al-Batran Salah-Eddin , Mueller Lothar , Thuss-Patience Peter C. , Borchert Kersten , Karatas Aysun , Keller Ralph , Klein Anja , Kranich Anne , Brenner Baruch , Lorenzen Sylvie , Lutz Manfred P. , Greil Richard , Tabernero Josep , Van Cutsem Eric , Graeven Ullrich 
Published: March 2020

TPS4158 Background: More than 50% of pts with esophageal cancer have locally advanced or metastatic disease at the time of initial diagnosis. For this group chemotherapy is increasingly used intending local and distant tumor control, improvement of quality of life (QoL) and longer survival. Previous data suggested that EGFR-targeting antibodies may be safely combined with cisplatin and 5-FU, and in addition may increase the efficacy of the standard cisplatin/5-FU regimen [Lorenzen et al, Ann Oncol2009; 20(10): 1667-1673]. Methods: In this open-label, randomized (1:1), multicenter, multinational phase III trial pts with nonresectable, advanced or metastatic ESCC, not eligible for definitive radiochemotherapy, are included. Pts have measurable or non-measurable disease according to RECIST 1.1 and an ECOG PS 0-1. Previous chemotherapy of ESCC in the metastatic setting, concurrent radiotherapy involving target lesions and previous exposure to EGFR-targeted therapy are excluded. Pts receive either CTX (cisplatin 100 mg/m² on day 1 and 5-FU 1000 mg/m²/d on day 1-4) or CTX + P (9 mg/kg on day 1). Cycles are repeated every 3 weeks until progression of disease. Tumor assessment is performed every 9 weeks. The primary objective is to demonstrate superiority of CTX + P over CTX alone in terms of overall survival. Secondary endpoints are progression-free survival, 1-year survival, response rate, safety and tolerability, and QoL. A translational analysis in tumor tissue and serum samples is included. 300 pts are planned to be enrolled for a power of 90% to reject the null hypothesis in which the median overall survival in the control and experimental groups are 6 and 9 months, respectively. 18 pts have been enrolled to date. A Data Monitoring Board will review safety data after 40, 100 and 200 pts. The clinical trial registry number is NCT1627379. Clinical trial information: NCT01627379.
Phase IIb randomized trial of Pexa-Vec (pexastimogene devacirepvec; JX-594), a targeted oncolytic vaccinia virus, plus best supportive care (BSC) versus BSC alone in patients with advanced hepatocellular carcinoma who have failed sorafenib treatment (TRAVERSE).
Authors: Heo Jeong , Chao Yee , Jonker Derek J. , Baron Ari David , Habersetzer Francois , Burke James , Breitbach Caroline , Patt Richard H. , Lencioni Riccardo , Homerin Michel , Limacher Jean-Marc , Lusky Monika , Hickman Theresa , Longpre Lara , Kirn David H. 
Published: March 2020

TPS4161^ Background: Pexa-Vec is a targeted oncolytic and immunotherapeutic vaccinia virus engineered to express human granulocyte-macrophage colony stimulating factor (GM-CSF). Direct oncolysis plus GM-CSF expression stimulates tumor vascular disruption and anti-tumor immunity (Nature Rev Cancer, 2009). Pexa-Vec 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 high vs low dose Phase 2 trial in 30 patients with advanced HCC, demonstrated prolonged survival in the high-dose Pexa-Vec arm (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 in patients with advanced HCC who have failed sorafenib treatment. Approximately 120 patients will be randomized 2:1 to Pexa-Vec plus BSC versus BSC, 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. 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. Assuming a median overall survival of 4.0 months with BSC 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 Pexa-Vec 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. Enrollment has begun on this study with clinical trial registry number of NCT01387555. Clinical trial information: NCT01387555.
The Borealis-2 clinical trial: A randomized phase II study of OGX-427 plus docetaxel versus docetaxel alone in relapsed/refractory metastatic urothelial cancer.
Authors: Rosenberg Jonathan E. , Hahn Noah M. , Regan Meredith M. , Jacobs Cindy , Stewart Patricia S. , Choueiri Toni K. 
Published: March 2020

TPS4588^ Background: Heat shock protein 27 (Hsp27) is over-expressed in many cancers including bladder, lung, prostate, and breast. Increased Hsp27 has been associated with inhibition of chemotherapy-induced apoptosis, increased tumor cytoprotection, and development of treatment resistance. OGX-427 is an antisense oligonucleotide designed to bind Hsp27 mRNA, inhibiting production of the Hsp27 protein. Inhibition of Hsp27 has been shown to increase apoptosis, inhibit tumor growth, and sensitize tumor cells to chemotherapy in a variety of malignancies, including urothelial cancer. Results of preclinical and phase 1 studies suggest that addition of OGX-427 to chemotherapy is well tolerated and may improve treatment efficacy. BOREALIS-2 is a randomized, multicenter, phase 2 study of OGX-427 in combination with docetaxel (DOC) vs. DOC alone in locally advanced/metastatic bladder cancer patients who received at least one line of prior platinum-based therapy. The primary objective is to evaluate overall survival. Secondary objectives include comparisons of safety and tolerability, disease response, and serum levels of Hsp27 and other pathway-related proteins. Associations between clinical outcomes, levels of Hsp27 and other proteins, and circulating tumor cells will be evaluated. Methods: Patients (N=200) are randomized in a 1:1 ratio following stratification (time from prior systemic chemotherapy; Bellmunt criteria). Up to 2 prior systemic therapies are allowed. Treatment-arm patients receive three loading doses of OGX-427 (600 mg) followed by up to ten 21-day treatment cycles (OGX-427 1000 mg on Days 1, 8, and 15 and DOC 75 mg/M2 IV on Day 1). Control-arm patients receive DOC 75 mg/M2 IV on Day 1 of each cycle. Treatment may continue until disease progression, unacceptable toxicity, completion of 10 cycles, or patient withdrawal. Patients who discontinue DOC due to toxicity after ≥2 cycles and do not have disease progression may receive maintenance therapy with OGX-427. One interim futility analysis will be performed. The trial will not be stopped early based on efficacy. Clinical trial information: NCT01780545.
ASPEN: A randomized phase II trial of everolimus versus sunitinib in patients with metastatic non-clear cell renal cell carcinoma.
Authors: Armstrong Andrew J. , Halabi Susan , Eisen Tim , Stadler Walter Michael , Jones Robert R , Vaishampayan Ulka N. , Garcia Jorge A. , Hawkins Robert E. , Kollmannsberger Christian K. , Lusk Christine , Broderick Samuel , George Daniel J. 
Published: March 2020

TPS4590 Background: Currently no level 1 evidence exists to guide therapeutic decisions in patients with metastatic non-clear cell renal cell carcinoma. Case series and retrospective analyses suggest that strategies targeting either the VEGF or mTOR/TORC1 pathways have clinical activity in papillary, chromophobe, or poorly differentiated histologic subtypes. Methods: We are conducting an international, randomized phase 2 trial of patients with metastatic non-clear cell RCC; either papillary, chromophobe, or undifferentiated histology; any Motzer risk group; and who have had no prior systemic therapy. All patients contribute tissue to an international biorepository for correlative genomic, genetic, and protein biomarker studies, along with companion longitudinal plasma and urine angiome studies. Patients are randomized to either everolimus or sunitinib (1:1) at FDA approved dosing until progression. The primary endpoint is progression free survival. Trial status: Seventy-three out of a planned 108 subjects have been enrolled at the time of abstract submission: median age 64, 59 white, 10 black, 4 unknown race, and includes 42 papillary and 31 chromophobe/undifferentiated histologies, 49 men and 22 women. Accrual is anticipated to be completed by December 2013. Accrual distribution by country is currently 43 (USA), 27 (UK), and 3 (Canada). The first DSMB meeting was conducted after 40 subjects completed at least 6 months of therapy and concluded that there were no unexpected safety signals and that the study should proceed. Tissue (primary, some metastatic, urine, plasma, whole blood) has been collected on all patients to date through the Duke Center for Human Genetics Biorepository. Clinical trial information: NCT01108445.
A phase II trial of the aurora kinase A inhibitor MLN8237 in patients with metastatic castrate resistant and neuroendocrine prostate cancer.
Authors: Beltran Himisha , Rubin Mark A. , Mosquera Juan Miguel , Christos Paul J. , Calukovic Olivera , Karpenko Irene , Pinski Jacek K. , Danila Daniel Costin , Nanus David M. , Tagawa Scott T. ,   The Prostate Cancer Clinical Trials Consortium
Published: March 2020

TPS5096 Background: NEPC can rarely arise de novo but more commonly arises as a mechanism of resistance in the setting of advanced prostate cancer. Transformation to NEPC is likely promoted by potent hormonal therapies and is currently under-recognized. There is no effective therapy for NEPC and most patients (pts) survive less than one year. We have found that Aurora kinase A (AURKA) and N-myc (MYCN) are significantly overexpressed and amplified in NEPC compared to prostate adenocarcinoma, and cooperate to induce neuroendocrine (NE) differentiation in prostate cancer (Beltran et al, Cancer Disc 2011). In preclinical models, aurora kinase inhibition results in dramatic and preferential anti-tumor activity in NEPC. Methods: In this single arm, multi-institutional Phase II trial, pts with metastatic prostate cancer need to meet at least one NEPC entry criterion: 1) histologic diagnosis of small cell or NEPC, 2) >50% immunohistochemical staining for NE markers, 3) development of liver metastases in absence of PSA progression, or 4) serum chromogranin >5x normal or neuron specific enolase >2x normal. Study will be open at 10 institutions including PCCTC sites. After a mandatory on-study research biopsy, pts will be treated with MLN8237, an orally administered Aurora kinase A inhibitor at 50 mg twice daily for 7 days repeated every 21 days. The primary endpoint is objective response rate (ORR). Secondary endpoints include overall survival, progression free survival, PSA response rate, circulating tumor cell response, and serum NE marker response to therapy. A number of correlative studies including AURKA, MYCN, AR, and exome and RNAseq are embedded in this trial in order to molecularly define this aggressive and poorly characterized disease. A Simon 2-stage design will be employed with up to 60 subjects providing 80% power to determine if the true ORR is >30% and 95% power if the true ORR is <15%, assuming a 5% level of significance. A subset of at least 20% meeting histologic entry criteria is embedded.
TAXYNERGY (NCT01718353): A randomized phase II trial examining an early switch from first-line docetaxel to cabazitaxel, or cabazitaxel to docetaxel, in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Antonarakis Emmanuel S. , Giannakakou Paraskevi , Kirby Brian J. , Nicacio Leonardo V. , Eisenberger Mario A. , Nanus David M. , Tagawa Scott T. 
Published: March 2020

TPS5100 Background: Docetaxel is the standard 1st-line chemotherapy for mCRPC, while cabazitaxel prolongs survival after docetaxel progression. The activity of cabazitaxel in the 1st-line setting is unknown, while the molecular mechanisms of taxane sensitivity/resistance have been understudied. Clinically, a ≥30% PSA decline within 3 months predicts survival in docetaxel- and cabazitaxel-treated men. Molecularly, emerging evidence suggests that sensitivity/resistance to taxanes relates to the ability of microtubules to traffic AR into the nucleus. Circulating tumor cells (CTCs) represent a real-time biomarker to assess drug-target engagement (DTE) which may be predictive of clinical outcome, and novel enrichment techniques present opportunities for molecular testing. Methods: This is a multicenter phase 2 trial for chemo-naïve mCRPC. 100 men will be randomized (2:1) to 1st-line docetaxel or cabazitaxel. Following 4 cycles, if a ≥30% PSA decline is not achieved, men will switch to the alternative taxane; others will remain on the initial taxane until progression (PCWG2) or unacceptable toxicity. CTCs will be obtained at screening, baseline, after 1 and 4 cycles of chemotherapy, at crossover and at progression to interrogate mechanisms of taxane sensitivity/resistance. CTCs will be enriched via a prostate-specific microfluidic device, enumerated, and analyzed via multiplex confocal microscopy for microtubule bundling and AR localization. TaqMan PCR (and RNA sequencing) will be used to detect AR variants, as preliminary data show that variant ARv567 predicts taxane sensitivity while ARv7 predicts resistance. The primary clinical endpoint of the trial is achievement of a ≥50% PSA reduction during the treatment continuum. The primary molecular endpoint is analysis of DTE in CTCs, and correlation with PSA responses. The study will have 80% power to detect a 25% increase in PSA response rate with tight interclass kappa coefficients for primary biomarkers. Secondary endpoints include radiographic and PSA progression-free survival, objective response rates, overall survival, and safety. Clinical trial information: NCT01718353.