bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alliance for clinical trials in oncology trial A021501: Preoperative extended chemotherapy vs. chemotherapy plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the head of the pancreas.
Authors: Katz Matthew H. G. , Ou Fang-Shu , Herman Joseph , Ahmad Syed A. , Wolpin Brian M. , Marsh Robert de Wilton , Shi Qian , Hubbard Joleen Marie , Meyerhardt Jeffrey A. , Chuong Michael , O'Reilly Eileen Mary 
Published: September 2018

TPS4151 Background: Borderline resectable pancreatic cancers infiltrate into adjacent vascular structures to an extent that makes an R0 resection unlikely when pancreatectomy is performed de novo. In a pilot study, Alliance for Clinical Trials in Oncology Trial A021101, the median survival of patients who received chemotherapy and radiation prior to anticipated pancreatectomy was 22 months, and an R0 resection was achieved in 64% of operations. However, the individual contributions of preoperative chemotherapy and radiation therapy are poorly defined.This study, Alliance for Clinical Oncology Trial A021501, will help define a standard preoperative treatment regimen for borderline resectable pancreatic cancer and position the superior arm for further evaluation in future phase III trials. Methods: In this recently activated randomized phase II trial, 134 patients with a biopsy-confirmed pancreatic ductal adenocarcinoma that meets centrally-reviewed radiographic criteria for borderline resectable disease are randomized to receive either 8 cycles of modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2 and infusional 5-fluorouracil 2400 mg/m2 for 4 cycles) or to 7 cycles of modified FOLFIRINOX followed by stereotactic body radiation therapy (33-40 Gy in 5 fractions). Patients without evidence of disease progression following preoperative therapy undergo pancreatectomy and subsequently receive 4 cycles of postoperative modified FOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and infusional 5-fluorouracil 2400 mg/m2 for 4 cycles). The primary endpoint is the 18-month overall survival rate of patients enrolled into each of the two treatment arms. An interim analysis of the R0 resection rate within each arm will be conducted to assess treatment futility after accrual of 30 patients. Secondary endpoints include rates of margin-negative resection and event-free survival. The trial is activated nationwide and eligible to be opened for accrual at any National Clinical Trials Network cooperative group member site. Clinical trial information: NCT02839343.
A phase III, double-blind, randomized clinical trial comparing S-1 in combination with DC vaccine loaded with WT1 peptides (TLP0-001) or placebo for the patients with advanced pancreatic cancer refractory to standard chemotherapy.
Authors: Katsuda Masahiro , Miyazawa Motoki , Kawai Manabu , Hirono Seiko , Okada Ken-Ichi , Shimizu Atsushi , Kitahata Yuji , Yamaue Hiroki 
Published: September 2018

TPS4153 Background: The development of new potent therapeutic is strongly called for treating pancreatic cancer. Dendritic cells (DCs) are a type of antigen-presenting cells that play an important role in adaptive immune system, and this property has prompted their recent application to therapeutic cancer vaccines. DCs loaded with tumor antigen ex vivo and administered as a cellular vaccine have been found to induce therapeutic anti-tumor immunity. Wilms' tumor gene WT1 is expressed in various kinds of cancers including pancreatic cancer. In pilot clinical trials of DC vaccination loaded with WT1 peptides for patients with advanced pancreatic cancer, induction of anti-tumor WT1 specific immune responses and tumor regressions have been observed (Kimura et al, Pancreas, 2012 / Kobayashi et al, Cancer Immunol Immunother, 2014 / Mayanagi et al Cancer Sci, 2015). TLP0-001 is activated Dendritic cells loaded with epitope peptides derived from WT-1. Methods: This is an investigator initiated, phaseIII, multicenter, double-blind, randomized trial of TLP0-001+S-1 versus placebo+S-1 for the patients with locally advanced or metastatic pancreatic cancer refractory to standard chemotherapy. Patients are allocated to either DC vaccine (TLP0-001) + S-1 group or placebo + S-1 in 1:1 ratio by dynamic allocation method. The primary endpoint is overall survival. Sample size is estimated presuming the effects will be observed from the time point of 50% cumulative survival rate. Assuming a type I error alpha (two-sided) level of 5% and a power of 80% or more for hazard ratio 0.644, sample size necessary is estimated as 174 patients. When the first 6 patients are administerd TLP0-001, the independent Data Monitoring Commitee checks safety data to assess continuation of the study. Enrollment begins in March 2017.
The ABC-study: A randomized phase III study comparing one course of adjuvant bleomycin, etoposide, and cisplatin (BEP) and one course of carboplatin AUC7 in clinical stage I seminomatous testicular cancer.
Authors: Tandstad Torgrim , Stahl Olof , Dahl Olav , Glimelius Ingrid , Haugnes Hege Sagstuen , Karlsdottir Asa , Langberg Carl Wilhelm , Soderstrom Karin , Solberg Arne , Stierner Ulrika K. , Wall Najme , Cohn-Cedermark Gabriella Elisabeth ,   SWENOTECA Group
Published: September 2018

TPS4593 Background: Clinical stage I seminomatous testicular cancer is by far the most frequent presentation of testicular cancer. Treatment options include surveillance or adjuvant treatment, internationally one course of adjuvant carboplatin (AUC7) is the preferred adjuvant treatment. Tumor size and stromal invasion in the rete testis can be used to identify patients with a higher risk of relapse. Recent data have showed only a modest effect of adjuvant carboplatin in preventing relapse, and more potent adjuvant therapies should be explored to this group of patients. Methods: The ABC-study is a investigator initiated randomized, open, phase III study comparing standard adjuvant chemotherapy in the form of one course carboplatin AUC7 to one course of BEP (Bleomycin, etoposide and cisplatin), in patients with one or two risk factors. Based on SWENOTECA data from one course of adjuvant carboplatin AUC7 we estimate the relapse rate in patients with one or two risk factors to be 9 %. We consider a reduction in relapse free survival of 7 % to be the minimum difference that will lead to routine use of one course of adjuvant BEP. To demonstrate an improvement in relapse rate from 9 to 2 % with an α = 0.05 and β = 0.80, 332 evaluable patients are required. We expect a dropout rate of maximum 5 %, and therefore intend to randomize a total of 348 patients. Enrollment in the study started in 2015, and as of February 1. 2017 a total of 66 patients have been enrolled. Accrual have been slower than expected, but the current accrual rate is about 6-7 patients a month. We invite institutions and collaboratory groups to participate in this study. NCT02341989. EUDRACT 2014-004075-23. Clinical trial information: NCT02341989.
A phase III randomized study comparing perioperative nivolumab vs. observation in patients with localized renal cell carcinoma undergoing nephrectomy (PROSPER RCC).
Authors: Harshman Lauren Christine , Puligandla Maneka , Haas Naomi B. , Allaf Mohamad , Drake Charles G. , McDermott David F. , Signoretti Sabina , Cella David , Gupta Rajan T , Bhatt Rupal Satish , Van Allen Eliezer Mendel , Choueiri Toni K. , Lara Primo , Kapoor Anil , Heng Daniel Yick Chin , Shuch Brian M. , Jewett Michael A.S. , George Daniel J. , Michaelson M Dror , Carducci Michael Anthony ,   On Behalf of the PROSPER RCC Investigators
Published: September 2018

TPS4596 Background: The anti-PD-1 antibody nivolumab (nivo) improves overall survival (OS) in metastatic treatment refractory RCC and is generally tolerable. In 2017, there is no standard adjuvant therapy proven to increase OS over surgery alone in non-metastatic (M0) disease. Mouse solid tumor models have revealed an OS benefit with a short course of neoadjuvant PD-1 blockade compared to adjuvant therapy. Two ongoing phase 2 studies of perioperative nivo in RCC patients (pts) have shown preliminary feasibility and safety with no surgical delays or complications. The PROSPER RCC trial will examine if the addition of perioperative nivo to radical or partial nephrectomy can improve clinical outcomes in pts with locally advanced RCC. With the goal of increasing cure and recurrence-free survival (RFS) rates in M0 RCC, we propose a three-pronged, multidisciplinary approach of presurgical priming with nivo followed by resection and adjuvant PD-1 blockade. Methods: Tumorbiopsy prior to randomization is mandatory to ensure the correct diagnosis and will permit unparalleled correlative science in this global, randomized, unblinded, phase 3 National Clinical Trials Network study. 766 pts with clinical stage ≥T2 or any node positive M0 RCC of any histology will be enrolled. The study arm will receive nivo 240mg IV for 2 doses prior to surgery followed by nivo adjuvantly for 9 months (q2 wks x 3 mo followed by q4 wks x 6 mo). The control arm will undergo the current standard of care: surgical resection followed by observation. Pts are stratified by clinical T stage, node positivity, and histology. There is 84.2% power to detect a 14.4% absolute increase in the primary endpoint of RFS from the ASSURE historical control of 55.8% to 70.2% at 5 yrs (HR 0.70). The study is also powered to detect a significant OS benefit (HR 0.67). Key safety, feasibility, and quality of life endpoints are incorporated. PROSPER RCC exemplifies team science with a host of planned correlative work to investigate the significance of the baseline immune milieu and changes after neoadjuvant priming and to identify predictive gene expression patterns. Additional collaborations are welcomed.
PROfound: A randomized Phase III trial evaluating olaparib in patients with metastatic castration-resistant prostate cancer and a deleterious homologous recombination DNA repair aberration.
Authors: De Bono Johann S. , Hussain Maha , Thiery-Vuillemin Antoine , Mateo Joaquin , Sartor A. Oliver , Chi Kim N. , Fizazi Karim , Twardowski Przemyslaw , Agarwal Neeraj , Sandhu Shahneen Kaur , Olmos David , Shore Neal D. , Saad Fred , Liu Sherry , Goessl Carsten Dietrich , Burgents Joe 
Published: September 2018

TPS5091 Background: The median overall survival for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) is short. Available agents may offer limited therapeutic benefit, but no molecularly stratified treatment has yet been approved for this heterogeneous disease. A sizable percentage of pts with mCRPC has loss of function aberrations in genes involved in homologous recombination repair (HRR) in tumor tissue, such as BRCA1/2 and ATM. These aberrations can confer sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition. A Phase II study indicated that the oral PARP inhibitor olaparib (Lynparza) had antitumor activity in 33% of mCRPC pts who had progressed after new hormonal agent (NHA) treatment and chemotherapy, with a strikingly higher composite response rate in pts with a deleterious HRR gene aberration (HRRa) (88%; 14/16) vs pts without a HRRa (6%; 2/33) (Mateo et al.2015). The PROfound study evaluates olaparib efficacy and safety versus physician’s choice of either abiraterone acetate or enzalutamide, in pts with mCRPC and a HRRa (NCT02987543). Methods: To be eligible for this multinational, open-label, Phase III study, mCRPC pts must have progressed on prior NHA treatment and have a tumor HRRa in one of 15 genes, as confirmed by an HRR Assay (Foundation Medicine, Inc.). Cohort A (n = 240 approx) includes pts with mutations in BRCA1, BRCA2 or ATM, while pts with a mutation in 12 other HRR genes will be assigned to Cohort B (n = 100 approx). Pts will be randomized (2:1) to olaparib tablets (300 mg orally bid) or physician’s choice of either enzalutamide (160 mg orally od) or abiraterone acetate (1000 mg orally od with 5 mg bid prednisone) and treatment continued until radiographic progression (as assessed by blinded independent central review) or lack of treatment tolerability. The primary endpoint of radiographic progression-free survival (rPFS) will be assessed in Cohort A using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria. Key secondary efficacy endpoints include confirmed objective response rate, time to pain progression, overall survival (all Cohort A) and rPFS (both cohorts combined). Clinical trial information: NCT02987543.
Abiraterone +/- cabazitaxel in defining complete response in prostatectomy (ACDC-RP) trial.
Authors: Joshua Anthony M. , Fleshner Neil Eric , Chin Joseph , Emmenegger Urban , Gleave Martin E. , Hotte Sebastien J. , Sweet Joan , Collins Colin , Boutros Paul Christopher , Lupien Mathieu , Pugh Trevor John , Chi Kim N. 
Published: September 2018

TPS5095 Background: Given recent advances in the management of de novo metastatic hormone-sensitive prostate cancer with both docetaxel and abiraterone, as well as evidence of significant activity of cabazitaxel in the post-abiraterone castrate-resistant setting, we hypothesized that the addition of cabazitaxel to neoadjuvant abiraterone will improve pathological complete response rates by overcoming mechanisms of resistance in localized high-risk prostate cancer. Aim: To determine the relative efficacy of the addition of cabazitaxel to abiraterone in the neoadjuvant treatment of prostate cancer to achieve a complete response. Methods: Open label, randomized, 2-arm multi-centre, phase 2 clinical trial. Primary endpoint: Pathological complete response rate (pCR). Secondary endpoints: surgical outcomes (positive margins, extracapsular extension, seminal vesicle or nodal involvement), pharmacodynamic markers in residual tumour (apoptosis, androgen receptor expression, localization, and signaling), biomarkers (intra-prostatic androgen levels), and safety. Design: Study participants will be randomized in a 1:1 ratio to receive either: Arm A: Abiraterone (1000 mg/day), prednisone (5 mg b.i.d.), leuprolide (22.5 mg s.c. every 3 months), and cabazitaxel (25 mg/m2 starting at week 2, with 6 mg pegfilgrastim 24 h following cabazitaxel) or Arm B: Abiraterone (1000 mg/day), prednisone (5 mg b.i.d.) and leuprolide (22.5 mg s.c. every 3 months). Assessments will take place biweekly for the first 12 weeks, then monthly until the prostatectomy (scheduled for 24 weeks following start of treatment). Target accrual is 88 participants within 36 months. Study is powered to detect a 15% difference with 85% power, assuming a one-sided type 1 error rate of 20%. A 6 patient safety run-in is included. As of Jan 2017, 1 site is open in Canada, with 4 additional Canadian sites and 1 site in Australia pending. To date, 4 participants are randomized and undergoing treatment. ACDC-RP is an investigator-initiated trial led by the Princess Margaret Urology Trials Group with funding from Ontario Institute for Cancer Research (OICR) and in-kind contributions from Janssen and Sanofi. Clinical trial information: NCT02543255.
Randomised phase III trial of enzalutamide in androgen deprivation therapy (ADT) with radiation therapy for clinically localised, high risk, or node-positive prostate cancer: ENZARAD (ANZUP 1303).
Authors: Williams Scott , Davis Ian D. , Sweeney Christopher , Stockler Martin R. , Martin Andrew James , Hague Wendy , Coskinas Xanthi , Yip Sonia , Tu Emily , Lawrence Nicola Jane , McDermott Ray , Kelly Paul J. , Deignan Olwyn , Hughes Simon , Fonteyne Valerie , Tombal Bertrand F. , Nguyen Paul L. ,   Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Published: September 2018

TPS5096 Background: Adjuvant ADT with an LHRH analog (LHRHA) given before, during and after radiotherapy (RT) is standard of care for high risk localised prostate cancer (PC). Enzalutamide is more effective in metastatic disease than conventional non-steroidal anti-androgens (NSAA). We hypothesize that addition of enzalutamide to adjuvant ADT and RT will improve outcomes. The aim is to determine the efficacy of enzalutamide compared with NSAA as part of adjuvant ADT with LHRHA in men planned for RT for localized high risk or node-positive PC. Methods: DESIGN: Open label, randomised, phase 3 trial including ANZ, USA, UK, Ireland and Europe. ENDPOINTS: OS (primary), cause-specific survival, PSA PFS, clinical PFS, time to subsequent hormonal therapy, time to castration-resistant disease (PCWG2 criteria), metastasis free survival, adverse events and HRQOL. Tertiary objectives: identification of prognostic/predictive biomarkers from archival tumour tissue and 4 serial fasting bloods. 800 target participants with 5.5 yrs minimum follow-up. 80% power to detect 33% reduction in the hazard of death assuming 5-year survival rate of 76% amongst controls. TREATMENT: Participants are randomised 1:1 to enzalutamide 160mg daily for 24 months versus conventional NSAA for 6 months. All participants receive LHRHA for 24 months and RT starting after week 16. RT delivered as 78Gy in 39 Fx or 46Gy in 23 Fx plus brachytherapy (nodal RT optional for N0, mandatory for N1). ASSESSMENTS: Baseline, then every 8 weeks until year 2, then 3-4 monthly until year 5, 6-monthly until year 7, then annually. CT/MRI and bone scan at baseline, PSA progression, 6 monthly until re-initiation of ADT, when PCWG2 criteria for CRPC are met and then 3 monthly until evidence of metastases. As of 1st February 2017, 55 of 67 sites open with 398 patients recruited. EORTC sites expected to open from Quarter 1 2017. ENZARAD is an investigator-initiated cooperative group trial led by ANZUP Cancer Trials Group with funds and product from Astellas. ANZUP is supported by Cancer Australia and previously CI NSW. ClinicalTrials.gov: NCT02446444, ANZCTR: ACTRN12614000126617 Clinical trial information: NCT02446444.
Clinical trial in progress: A phase 3 study of maintenance bi-shRNA-furin/GM-CSF-expressing autologous tumor cell vaccine in women with stage IIIb-IV high-grade epithelial ovarian cancer.
Authors: Oh Jonathan , Barve Minal A. , Tewari Devansu , Chan John K. , Grosen Elizabeth , Rocconi Rodney Paul , Stevens Erin Elizabeth , DeMars Leslie Robbins , Ghamande Sharad A. , Coleman Robert L. , Manning Luisa , Wallraven Gladice , Senzer Neil N. , Birkhofer Martin , Nemunaitis John J. 
Published: September 2018

TPS5604 Background: Vigil is an immuno-stimulatory autologous cellular therapy, which uses patient tumor cells transfected with a plasmid encoding genes for GM-CSF and furin (to down regulate TGFβ 1&2). In Phase I, systemic immune activation was demonstrated in the majority of patients using an IFNƔ ELISPOT assay. A randomized Phase 2 assessment of Vigil maintenance therapy vs. observation in ovarian cancer demonstrated prolonged relapse free survival (RFS) (Oh J, Barve M, et al. Gynecologic Oncology, 2016; 143: 504–510.). Based on these observations, a Phase 3 study of maintenance Vigil therapy in patients with advanced ovarian cancer was initiated (NCT02346747). Methods: This is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 study of maintenance Vigil in women with Stage IIIb,c or IV high-grade papillary serous/clear cell/ endometrioid ovarian, fallopian tube or primary peritoneal cancer. Patients will have a minimum of 4 and a maximum of 12 Vigil doses manufactured from tumor obtained at primary debulking surgery. Patients must achieve a complete clinical remission following primary surgery and chemotherapy before being randomized 1:1 to receive either monthly intradermal Vigil or placebo. Randomization is stratified by extent of surgical cytoreduction (complete/microscopic vs. macroscopic residual disease) and neoadjuvant vs. adjuvant chemotherapy. The primary objective is to compare RFS of subjects randomized to Vigil vs. placebo, and the key secondary objective is overall survival (OS). The sample size calculation of 222 patients assumes 24 months for accrual and 36 months of follow-up with a median RFS of 19 months from randomization, in the control group. This provides 90% power to detect a hazard ratio (HR) of 0.6 favoring Vigil at the 0.05 level of significance. To date, 61 patients have been randomized and an additional 55 patients are receiving chemotherapy in anticipation of randomization. Tumor tissue is being obtained from approximately 20 patients per month at multiple sites across the U.S. At their last meeting in January, 2017 the independent DSMB recommended that the study continue without change. Clinical trial information: NCT02346747.
A phase 2 study to assess olaparib by homologous recombination deficiency status in patients with platinum-sensitive, relapsed, ovarian, fallopian tube, or primary peritoneal cancer.
Authors: Cadoo Karen Anne , Aghajanian Carol , Fraser Cindy , Milner Alvin , Kolvenbag Geert 
Published: September 2018

TPS5606 Background: The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib is approved for treatment of patients (pts) with germline BRCA mutations ( BRCAm) and advanced ovarian cancer (OC). BRCA mutations are genetic alterations leading to homologous recombination deficiency (HRD) and tumor susceptibility to DNA-damaging agents, including PARP inhibitors. Loss of genetic heterozygosity, telomeric-allelic imbalance, or large-scale state transitions may identify additional pts who could benefit from PARP inhibitor therapy. Methods: LIGHT is a non-randomized, open-label, phase 2 study to assess the efficacy and safety of olaparib in patient cohorts identified by different HRD genetic tests (NCT02983799). Patients will have platinum-sensitive (progression > 6 mo after the end of the last platinum-based chemotherapy), relapsed, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer; ECOG performance status 0–1; and ≥2 prior lines of platinum-based chemotherapy for OC. Key exclusion criteria include prior PARP inhibitor treatment; concomitant use of potent CYP3A4/5 inhibitors or inducers; and symptomatic uncontrolled brain metastases. Patients will be enrolled into 4 cohorts of 30 pts each based upon BRCAm or tumor HRD status determined by genetic test results: germline BRCAm; somatic BRCAm; MyChoice HRD-positive and wildtype BRCAm; MyChoice HRD-negative and wildtype BRCAm. All pts will receive 300 mg olaparib tablets twice daily until disease progression (RECIST v1.1) or unacceptable toxicity. The primary endpoint is investigator-assessed objective response rate (ORR) according to RECIST v1.1 criteria. The maximum precision of the ORR is approximately ±18.7% for 30 pts. Secondary endpoints include duration of response, cancer antigen-125 response rate, disease control rate, progression-free survival, time to any progression, overall survival, and homologous recombination repair gene panel mutation status related to clinical outcome. Planned enrollment of 120 pts at sites in the United States was initiated in December 2016. Clinical trial information: NCT02983799.