bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase III, multicenter study to assess the diagnostic performance and clinical impact of 18F-DCFPyL PET/CT in men with suspected recurrence of prostate cancer (CONDOR).
Authors: Morris Michael J. , Pouliot Frederic , Saperstein Lawrence , Rowe Steven P. , Gorin Michael A. , Josephson David Y. , Wong Jeffrey Y.C. , Carroll Peter , Lin Tess , Stambler Nancy , Wong Vivien , Jensen Jessica Donato , Siegel Barry A. 
Published: May 2019

TPS5093 Background: Early and accurate detection of recurrent or metastatic prostate cancer remains an unmet diagnostic need for patient management. While agents for positron emission tomography (PET), such as 11C-choline and 18F-fluciclovine, have emerged as options for imaging recurrent prostate cancer, these agents are not specific for the disease. 18F-DCFPyL is a novel, low-molecular weight, PET radiopharmaceutical that binds selectively to prostate-specific membrane antigen with high affinity. In prior studies, 18F-DCFPyL PET/CT has shown reliable diagnostic performance in detecting metastatic or recurrent prostate cancer (Rowe Mol Imaging Biol 2016 18:411-19; Gorin J Urol 2018 1999:126-32). Methods: CONDOR is a phase 3, multicenter, open-label study designed to assess the diagnostic performance and clinical impact of 18F-DCFPyL PET/CT in men with suspected recurrent or metastatic prostate cancer. Approximately 200 patients are planned to be enrolled across 15 centers in the United States and Canada. Eligible patients ≥18 years of age must have histologically confirmed prostate adenocarcinoma, have rising PSA after definitive therapy, and negative or equivocal conventional imaging. A single 9 mCi (333 MBq) dose of 18F-DCFPyL is administered, followed by whole body PET/CT scan 1 hour later. The primary objective is to assess the correct localization rate (percentage of patients with a one-to-one correspondence between localization of at least one lesion identified on 18F-DCFPyL PET/CT and the composite truth standard, defined as either evaluable histopathology, informative correlative imaging, or PSA response after radiation therapy). Additional study objectives include safety and tolerability of 18F-DCFPyL, impact on intended treatment plans, detection rates and PPV of 18F-DCFPyL by region, and detection rates by baseline PSA. 18F-DCFPyL PET/CT results are centrally reviewed by independent readers blinded to all clinical and other imaging information. As of February 9, 2019, a total of 36 patients have been dosed in the study. Clinical trial information: NCT03739684.
High dose testosterone in men with metastatic castrate-resistant prostate cancer (mCRPC) and homologous recombination deficiency (HRD).
Authors: Chen Julia , Joshua Anthony M. , Denmeade Samuel R. , Antonarakis Emmanuel S. , Crumbaker Megan 
Published: May 2019

TPS5095 Background: mCRPC progresses via adaptive mechanisms that allow ongoing androgen receptor (AR) signalling despite castrate levels of androgens. Bipolar androgen therapy (BAT), cycling between supraphysiologic and subphysiologic serum testosterone levels, aims to exploit these adaptations to induce tumor regression. Extensive clinical data demonstrate the safety and efficacy of BAT in men with asymptomatic mCRPC. However, de novo resistance is still common and predictive biomarkers to refine patient selection are lacking. Pre-clinical data suggest that the induction of double-stranded DNA (dsDNA) breaks by BAT may be crucial to its mechanism of action. DNA repair defects, such as HRD, are particularly relevant in CRPC patients. We hypothesize that CRPC patients with DNA repair deficits such as HRD, may be particularly responsive to BAT. Methods: This is a phase II prospective single arm interventional trial (NCT03522064). Up to 30 patients will be recruited based on a Simon two-stage design with a power of 90% to detect an increase in response rate from 20% to 40%. Key inclusion criteria include i) asymptomatic or minimally symptomatic mCRPC, ii) rising PSA despite a castrate serum testosterone and iii) HRD on germline, tumor and/or circulating tumor DNA (ctDNA) analysis. Key exclusion criteria include i) ADT < 1 year, ii) disease extent/sites that would cause significant risk if tumor flare occurs (e.g.: brain) and iii) significant cardiac disease. Previous PARP inhibitor therapy will be permitted in a subset. Participants will receive IM testosterone enanthate 500mg q4w in combination with ongoing LHRH antagonist/agonist or orchidectomy. The primary endpoint is PSA response rate defined as PSA reduction ≥50% from baseline. Secondary endpoints include time to PSA progression, quality of life, radiologic response and safety and tolerability. Exploratory endpoints include changes in ctDNA and tumoral DNA alterations from baseline to progression. Accrual is ongoing. Clinical trial information: NCT03522064.
Focal radiation for oligometastatic castration-resistant prostate cancer (FORCE): A phase II randomized trial.
Authors: Reichert Zachery , Smith David C. , Morgan Todd Matthew , Piert Morand , Tomlins Scott A. , Cackowski Frank Cameron , Caram Megan Veresh , Hearn Jason W.D. , Palmbos Phillip Lee , Schonewolf Caitlin , Yentz Sarah Elizabeth , Spratt Daniel Eidelberg 
Published: May 2019

TPS5096 Background: Metastasis Directed Therapy (MDT) is the focus of recently completed and ongoing clinical trials. For biochemically recurrent prostate cancer, MDT delays the initiation of androgen deprivation, but is noncurative as > 75% of patient’s progress within 3 years. In metastatic castration-resistant prostate cancer (mCRPC), focal therapies are common for palliation of pain, but not routinely recommended for controlling systemic disease. Whole genome sequencing has demonstrated that mCRPC metastases seed new metastases and patients with a greater burden disease develop more rapid resistance to next-generation hormone therapies. Therefore, MDT to all visible disease may be beneficial in oligometastatic CRPC. Methods: This is a prospective, randomized phase 2 clinical trial with a primary endpoint of progression-free (radiographic + clinical) survival at 18 months. Secondary endpoints include objective disease PFS, PSA PFS, PSA response rate, non-irradiated distant MFS and PROs. The utility of 68Ga-PSMA PET/CT will be explored and sequential analysis of circulating tumor DNA/circulating tumor cells will be done. Sites of disease are defined by all available imaging (minimum of CT or MRI, NM bone scan, but potentially molecular imaging). Oligometastatic CRPC is defined as between 1 and ≤5 treatment sites. Eligible patients with progressive oligometastatic CRPC may have prior sipuleucel-T but no therapy for mCRPC. Docetaxel or abiraterone within the hormone sensitive phase is allowed. Patients will be randomized 1:1 (stratified by 1-2 vs 3-5 oligometastases and whether molecular imaging in mCRPC is available) to physician’s choice vs. physician’s choice + MDT. MDT may be delivered via multiple radiation oncology techniques to cytotoxic doses. If the prostate itself has not been treated (on MDT arm), it will be treated and count as 1 site. Statistical analysis will provide objective PFS by arm with associated 90% confidence intervals. The study is recruiting 72 randomized patients at the University of Michigan Rogel Cancer Center and soon the Ann Arbor Veteran’s Administration Hospital. The trial is funded by the Prostate Cancer Foundation and a University of Michigan Cancer Center Trial Support Award. Clinical trial information: NCT03556904.
VISION: An international, prospective, open-label, multicenter, randomized phase 3 study of 177Lu-PSMA-617 in the treatment of patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC).
Authors: Sartor A. Oliver , Morris Michael J. , Krause Bernd J 
Published: May 2019

TPS5099 Background: The novel therapeutic drug 177Lu-PSMA-617 is a prostate specific membrane antigen (PSMA) targeting agent to deliver radionuclide therapy for the treatment of pts with metastatic castration resistant prostate cancer. Based on preclinical data that demonstrated high PSMA binding affinity & compound internalization, prolonged tumor uptake, rapid kidney clearance, & high tumor-to-background ratio, 177Lu-PSMA-617 proceeded into clinical development. Preliminary clinical evidence indicates 177Lu-PSMA-617 may demonstrate clinical benefit in pts with mCRPC in a setting where pts had no recommended standard of care. This Phase 3 study will assess the efficacy of 177Lu-PSMA-617 in patients with progressive PSMA-positive mCRPC by measuring overall survival (OS) and radiographic progression free survival (rPFS) in a randomized, prospective, open-label trial. Methods: The primary objective of this study is to compare the 2 alternative endpoints of rPFS & OS in pts with progressive PSMA-positive mCRPC who receive 177Lu-PSMA-617 in addition to best supportive/standard of care vs pts treated with best supportive/best standard of care alone. Eligibility criteria are: PSMA expressing tumor; prior exposure to a taxane and novel androgen axis drug. Pts will be randomized in a 2:1 ratio in favor of the investigational arm with stratification factors of LDH, liver disease, ECOG score, and use of NAAD at time of randomization as a standard of care. Under the alternative hypothesis, median OS on active is assumed to be 13.7 mo for a HR of 0.7306 and rPFS on the active is assumed to be 6 mo for a HR of 0.67. Planned enrollment for this study is 750 patients. Enrollment began in June 2018 and continues; the IDMC last reviewed the trial for safety in January 2019 and suggested that the trial continue as planned. Clinical trial information: NCT03511664.
Trial in progress: Phase II study of stereotactic body radiation therapy and atezolizumab in the management of recurrent, persistent, or metastatic cervical cancer.
Authors: Ahmed Kamran A. , Kim Youngchul , Apte Sachin M. , Chon Hye Sook , Chern Jing-Yi , Conejo-Garcia Jose , Fernandez Daniel Celestino , Hoffman Mitchel , Kim Sungjune , Lam Cesar , Montejo Michael E. , Shahzad Mian M. , Wenham Robert Michael 
Published: May 2019

TPS5596 Background: There is no consistent recommendation for management of metastatic cervical cancer beyond first line therapy with chemotherapy and bevacizumab. Pembrolizumab is now approved for PD-L1 positive or MSI-H/dMMR metastatic or recurrent cervical cancer. Numerous pre-clinical studies have provided evidence to combine radiation therapy with immune checkpoint inhibition to improve response rates. The evidence is strongest for short course, hypofractionated radiation regimens. We hypothesize treatment with atezolizumab with hypofractionated radiation therapy will improve objective response rate (ORR) compared with atezolizumab alone in patients with recurrent, persistent, or metastatic cervical cancer. Methods: The study is designed as a prospective, single arm, nonrandomized, open-label, phase II trial of stereotactic body radiation therapy (SBRT) with 24 Gy in 3 fractions to patients with ≥ 2 metastatic sites followed 1 week later by atezolizumab (1200 mg IV every 3 weeks) for patients with recurrent, persistent, or metastatic cervical cancer. Dose reductions will not be allowed. The primary objective of the study is to evaluate the ORR by Immune-Modified Response Evaluation Criteria in Solid Tumors (irRECIST) criteria following SBRT and atezolizumab. Secondary endpoints include progression free survival, overall survival, local control, and adverse events. Correlative aims include assessing blood and tissue biomarkers (i.e. PD-L1, mutation burden, TCR repertoire etc.) for association with clinical benefit. A total of 26 patients will be enrolled. An interim analysis will be performed to assess efficacy after 13 patients become evaluable.This study is open with 2 patients enrolled at the time of submission. Clinical trial information: NCT03614949.
EUDARIO/ENGOTov-48: A European multicenter randomised phase II trial on the combination of the HSP90 inhibitor ganetespib with carboplatin followed by maintenance treatment with niraparib (+/- ganetespib) compared to platinum-based combination-chemotherapy followed by niraparib in relapsed platinum-sensitive ovarian cancer patients.
Authors: Concin Nicole , Lorusso Domenica , Braicu Ioana , Ray-Coquard Isabelle Laure , Joly Florence , Harter Philipp , Wimberger Pauline , Lotz Jean-Pierre , Zeimet Alain G , Scambia Giovanni , Schmalfeldt Barbara , Zamagni Claudio , Raspagliesi Francesco , Mustea Alexander , Ulmer Hanno , Kramer Daniela , Dobbelstein Matthias , Pujade-Lauraine Eric , Sehouli Jalid , Vergote Ignace 
Published: May 2019

TPS5605 Background: Carboplatin (C) mainly acts by forming interstrand crosslinks (ICL) within the DNA double helix, which can only be removed by the Fanconi Anemia (FA) pathway. HSP90 inhibitors destabilise a number of HSP90 client proteins, such as those governing the FA DNA repair pathway and the G2/M checkpoint (e.g. Chk1 and Wee1). Kramer et al. (Cell Death Differ, 2017) showed that the HSP90 inhibitor Ganetespib (G) virtually eliminates a functional FA DNA repair complex, therewith preventing the repair of DNA ICL in vitro and vivo. In parallel, G abrogated Chk1 and Wee1 expression and circumvented a G2/M arrest. Consequently, cells with unrepaired DNA damage rushed into mitosis, which resulted in massive tumour cell death. Furthermore, HSP90 inhibition has been shown to reduce the amount of BRCA1 in the cell therewith broadening sensitivity towards PARPi and preventing acquired PARP resistance. Our trial approach is tested in ovarian carcinomas with a mutant p53 background. EUDARIO (EUDRACT 017-004058-40) is funded by the European Commission (FP7 project GANNET53). Methods: Eligible patients have relapsed platinum-sensitive ovarian cancer, no limits in prior lines, high-grade (but clear cell) histology or carcinosarcoma, disease measurable or evaluable according to RECIST 1.1. Patients are randomised into 3 treatment arms (1:1:1), a) control arm: C+Gemcitabine or C+Paclitaxel (q3w, 6 cycles, investigator`s choice) followed by Niraparib, b+c) 2 experimental arms: C (AUC5, d1) + G (150mg/m2, d1) q3w 6 cycles followed by either Niraparib alone (arm b) or by Niraparib+G (arm c; G at 100mg/m2 weekly, limited to 9 months). Niraparib (200/300mg/day) is given in case of SD, PR or CR after platinum-based treatment until disease progression. The main analysis will combine both experimental arms b+c and jointly compare them against arm a using log-rank test. Primary endpoint is PFS, secondary endpoints are PFS2, TFST, TSST, safety, ORR, PRO, OS. The first patient was dosed in January 2019. Clinical trial information: NCT03783949.
AtTEnd/ENGOT-en7: A multicenter phase III double-blind randomized controlled trial of atezolizumab in combination with paclitaxel and carboplatin in women with advanced/recurrent endometrial cancer.
Authors: Colombo Nicoletta , Barretina-Ginesta Maria Pilar , Beale Philip James , Harano Kenichi , Hudson Emma , Marmé Frederik , Marth Christian , Radaglio Manuela , Secord Angeles Alvarez , Fossati Roldano , Roberto Anna , Rulli Eliana , Tettamanzi Francesca , Biagioli Elena 
Published: May 2019

TPS5608 Background: Prognosis of advanced/recurrent endometrial cancer (EC) is poor with median survival of 12-15 months for patients with measurable disease. Treatment options are limited, with primary management being chemotherapy with carboplatin and paclitaxel. EC is known to be one of the tumor types with highest mutational load. Ultra- and hyper-mutated EC, which harbor POLE and mismatch repair gene defects respectively, have shown peri-tumoral T cell infiltration and high expression of PD-1 and PD-L1 proteins, suggesting that immune regulation may enhance specific T cell responses and result in improved anti-tumour immunity. Preliminary data in EC patients have shown tumour control activity of the PD-L1 targeting agent atezolizumab. Methods: 550 patients with newly diagnosed, advanced stage III/IV or recurrent EC will be accrued during a period of 24 months with a 1:2 randomization ratio into two arms: i. control group receiving standard chemotherapy plus placebo IV every 21 days up to 6/8 cycles followed by placebo until progression; ii. experimental group receiving standard chemotherapy plus 1200 mg atezolizumab IV every 21 days up to 6/8 cycles followed by atezolizumab until progression. Standard chemotherapy will consist of 175 mg/m2 paclitaxel plus AUC5/6 carboplatin. Stratification factors are: histology, disease stage, microsatellite status, country of experimental site. The study is planned to demonstrate a survival increase and is equally powered for PFS. Secondary endpoints include ORR, duration of response, PFS2, quality of life, adverse events and compliance. The study is sponsored by MaNGO group and will involve sites from ENGOT and GCIG networks across Europe, Japan, Australia and New Zealand. Currently, the trial is open in Italy and in Switzerland where a total of 6 patients have been enrolled. Clinical trial information: NCT03603184.
Phase II trial of nivolumab with chemotherapy as neoadjuvant treatment in inflammatory breast cancer.
Authors: Kwa Maryann J. , Tray Nancy , Esteva Francisco J. , Novik Yelena , Speyer James L. , Oratz Ruth , Meyers Marleen Iva , Muggia Franco , Ty Victor , Troxel Andrea , Schneider Robert , Adams Sylvia 
Published: May 2019

TPS604 Background: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer with poor prognosis and is often resistant to neoadjuvant chemotherapy with risk of early recurrence and systemic spread of disease. PD-L1 expression in IBC is frequent (Bertucci et al. Oncotarget 2015), and blockade of the PD-1/PD-L1 axis with checkpoint inhibitors has emerged as a promising treatment to enhance anti-tumor immunity and clinical response. We hypothesize that PD-1 blockade with nivolumab in combination with neoadjuvant (primary) chemotherapy will increase the rate of pathologic complete response (pCR) and reduce risk of recurrence in patients with IBC. Methods: This is a single-arm open-label multicenter phase II study of nivolumab with neoadjuvant chemotherapy in patients with non-metastatic IBC (n = 52) (ClinicalTrials.gov: NCT03742986). All breast cancer subtypes (based on ER/PR/HER2) will be allowed. Patients will receive nivolumab 360 mg IV on day 1 (21-day cycle) for four cycles in addition to standard chemotherapy. Cohort 1 (patients with triple negative breast cancer or hormone receptor-positive (HR)/HER2-negative IBC) will receive nivolumab in combination with paclitaxel followed by doxorubicin and cyclophosphamide (AC). Cohort 2 (patients with HER2-positive IBC) will receive nivolumab in combination with a taxane (docetaxel or paclitaxel), trastuzumab, and pertuzumab followed by AC. All patients will then undergo mastectomy followed by radiation. The primary study objective is pCR rate (ypT0/Tis ypN0). Secondary objectives will be safety, tolerability and invasive recurrence-free interval. Association of correlative biomarkers with pCR and sensitivity or resistance to therapy with the combination of nivolumab and chemotherapy will be evaluated. Analyses will include mutational and neoantigen load, tumor-infiltrating lymphocytes (TILs) by histopathological assessment, T-cell receptor (TCR) by immunosequencing, and immune gene profiles in the tumor. PD-L1 expression in tumor tissue is not required for enrollment but will be assessed as a predictive marker. Clinical trial information: NCT03742986.
NSABP B-59/GBG 96-GeparDouze: A randomized double-blind phase III clinical trial of neoadjuvant chemotherapy (NAC) with atezolizumab or placebo in patients (pts) with triple-negative breast cancer (TNBC) followed by adjuvant atezolizumab or placebo.
Authors: Geyer Charles E. , Loibl Sibylle , Rastogi Priya , Seiler Sabine , Costantino Joseph P. , Nekljudova Valentina , Cortazar Patricia , Lucas Peter C. , Denkert Carsten , Mamounas Eleftherios P. , Jackisch Christian , Wolmark Norman 
Published: May 2019

TPS605 Background: TNBC is associated with higher percentages of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC), and women with a pCR have a favorable prognosis. However, Liedtke (2008) and Loibl (2017) found that women with residual disease have a substantially higher risk of recurrence than women with other subtypes of breast cancer. Additionally, Adams (2017) and Schmid (2017) found that therapeutic blockade of PD-L1 binding by atezolizumab has resulted in relevant anti-tumor efficacy. Methods: Design: This is a phase III, double blind, placebo-control trial evaluating neoadjuvant atezolizumab with NAC followed by adjuvant atezolizumab in TNBC. Pts are stratified by region (North America; Europe), tumor size (1.1-3.0cm; >3.0cm), AC/EC schedule (q2w; q3w), nodal status (positive; negative), and PD-L1 status (positive; negative or indeterminate) then randomized 1:1 to receive atezolizumab/placebo 1200 mg IV every 3 wks concurrently with both sequential regimens of weekly paclitaxel 80 mg/m2 IV for 12 doses with every 3-wk carboplatin AUC of 5 IV for 4 doses followed by AC/EC every 2-3 wks (per investigator discretion) for 4 cycles. Following surgery, pts resume atezolizumab/placebo 1200 mg IV every 3 wks as adjuvant therapy for 6 months. Radiotherapy based on local standards is co-administered with atezolizumab/placebo. Eligibility criteria: Centrally confirmed ER-neg, PR-neg, HER2-neg invasive breast cancer by ASCO/CAP guidelines. Primary tumor must be stage T2 or T3 if cN0 or cN1 with negative biopsy or T1c, T2, or T3 if cN1 with positive biopsy or cN2 or cN3. LVEF >55% and no significant cardiac history. Statistical methods: Co-primary endpoints are event-free survival (EFS) and pCR breast/nodes. Secondary endpoints include pCR breast, overall survival, distant disease-free survival, safety and toxicity. Trial is an academic collaboration between NSABP and GBG with support from Genentech/Roche. Support: Genentech/Roche. Clinical trial information: NCT03281954.