bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pamiparib, an investigational PARP inhibitor, in patients with metastatic castration-resistant prostate cancer (mCRPC) and a circulating tumor cell (CTC) homologous recombination deficiency (HRD) phenotype or BRCA defects: A trial in progress.
Authors: Chowdhury Simon , Mateo Joaquin , Gross Mitchell , Armstrong Andrew J. , Cruz-Correa Marcia , Piulats Josep M. , Blay Jean-Yves , Li Miao , Rivas Delcia , Quintero Luis , Castro Henry , Nkobena Andong , Raponi Mitch , Pelham Robert , Landers Mark , Montgomery Robert B. 
Published: May 2019

TPS5086 Background: Men with mCRPC who have a BRCA1/2 mutation ( BRCA1/2mut) or mutations in other genes resulting in HRD have a poor prognosis. A novel liquid biopsy test (EPIC Sciences) identifies CTCs with an HRD phenotype. Preliminary studies showed that these men may respond to treatment with a PARP inhibitor. Pamiparib, an investigational PARP1/2 inhibitor, has shown brain penetration and potent PARP–DNA complex trapping in nonclinical studies. In early phase clinical studies (NCT02361723; NCT03333915), pamiparib was generally well tolerated and showed preliminary antitumor activity; 60 mg orally twice daily (BID) was established as the recommended investigational dose. Methods: This open-label, global, phase 2 study (NCT03712930) evaluates the antitumor activity and safety/tolerability of pamiparib in mCRPC patients (pts) with CTC-HRD, assessed by the CTC-HRD assay, or deleterious germline/somatic mutations in BRCA1/2. Patients must have progressed on/after ≥1 androgen receptor-targeted therapy, received ≥1 taxane-based therapy, and have prostate-specific antigen (PSA) progression per PCWG3 criteria. Four cohorts of pts will receive pamiparib 60 mg BID in 28-day cycles. Cohort 1 will include ~50 pts with CTC-HRD+ +/- BRCA1/2mut mCRPC with measurable metastatic disease; Cohort 2 will include ~30 pts with CTC-HRD+ +/- BRCA1/2mut mCRPC with bone-only disease; Cohorts 3 & 4 will include ~20 pts with CTC-HRD-/unk + BRCA1/2mut mCRPC with measurable metastatic disease (Cohort 3), or bone-only disease (Cohort 4). Disease status will be assessed every 8 wks for 24 wks, then every 12 wks; PSA levels will be tested every 4 wks. Co-primary endpoints are radiographic ORR assessed by IRC (pts with measurable disease) and confirmed PSA response rate per PCWG3 criteria (pts +/- measurable disease). Secondary endpoints include ORR, time to PSA response/progression, duration of PSA response, time to symptomatic skeletal event, radiographic progression-free survival, overall survival, and safety. As of 05 December 2018, this study is actively enrolling. Clinical trial information: NCT03712930.
Cabazitaxel with abiraterone versus abiraterone alone randomized trial for extensive disease following docetaxel: the CHAARTED 2 Trial: A trial of the ECOG-ACRIN Cancer Research Group (EA8153).
Authors: Kyriakopoulos Christos , Chen Yu-Hui , Duan Fenghai , Jeraj Robert , Luo Jun , Antonarakis Emmanuel S. , Liu Glenn , Carducci Michael Anthony 
Published: May 2019

TPS5094 Background: The E3805 CHAARTED trial showed a significant survival benefit from early treatment with docetaxel in patients (pts) with high-volume metastatic hormone-sensitive prostate cancer (HSPC). However, eventually all these patient will develop castration-resistant disease (CRPC) and it is currently unknown what is the optimal treatment in that setting. We hypothesize that treatment with a second round of chemohormonal therapy –this time in the CRPC setting- will improve outcomes. Methods: This is a prospective randomized phase II open label trial led by ECOG-ACRIN. Pts (N = 210) with metastatic CRPC who have previously received docetaxel for HSPC will be randomized to 2 treatment arms (1:1): abiraterone/prednisone plus cabazitaxel for up to 6 cycles versus abiraterone/prednisone alone. Stratification factors include ECOG performance status, time from initiation of ADT to development of CRPC and visceral versus bone only metastases. The primary objective is to evaluate the efficacy of abiraterone/prednisone plus cabazitaxel versus abiraterone/prednisone alone. The primary endpoint of the trial is progression-free survival (PFS), defined clinically or radiographically. Secondary endpoints include PSA response, radiographic response, time to PSA progression, overall survival and safety. Exploratory objectives include response assessment based on AR-V7 status as well as by NaF PET/CT imaging. Key inclusion criteria include: metastatic CRPC, prior treatment with at least 3 cycles of docetaxel for metastatic HSPC, no prior treatment for CRPC (radium-223 or sipuleucel-T excluded), ECOG performance status of 0-2 and peripheral neuropathy of less than 2. The study was activated on 02/08/2018. As of 01/21/2019, 28/210 pts have been enrolled. Support: CA180820, CA180794, CA180799, CA180802; and Genzyme Corporation, a subsidiary of Sanofi S.A. Clinical trial information: NCT03419234.
A phase II Salvage Trial of AR Inhibition with ADT and Apalutamide with Radiation therapy followed by docetaxel in men with PSA recurrent prostate cancer (PC) after radical prostatectomy (STARTAR).
Authors: Zhang Tian , Koontz Bridget F. , Tagawa Scott T. , Nagar Himanshu , Bitting Rhonda L. , Frizzell Bart , Rasmussen Julia , Wilder Rhonda , Anand Monika , Winters Carolyn , Riggan Colleen , Lee Aileen , Healy Patrick , Wu Yuan , McNamara Megan Ann , Harrison Michael Roger , George Daniel J. , Armstrong Andrew J. 
Published: May 2019

TPS5097 Background: Androgen deprivation combined with salvage external beam radiation therapy (RT) have improved survival for patients (pts) with non-metastatic hormone naïve PC and PSA recurrence after radical prostatectomy (RP). Our recent STREAM trial showed addition of enzalutamide to RT and ADT had a 3-year progression free survival (PFS) of 53%. Adding effective PC treatments in this setting may further improve 3-year PFS. Methods: STARTAR is an investigator-initiated phase 2 trial for salvage treatment of biochemically recurrent PC following prostatectomy. Key inclusion criteria include histologic prostate adenocarcinoma, either Gleason 7 with T3/positive margin/1-4 positive lymph nodes or Gleason 8-10 disease, PSA relapse within 4 years of prostatectomy (minimum PSA 0.2 ng/mL to maximum PSA 4 ng/mL). Treatment involves ADT with apalutamide for 9 months, continue with with prostate bed +/- nodal RT at month 3, followed by 6 cycles of docetaxel 75mg/m2 IV every 3 weeks for 6 cycles. The primary endpoint of the study is 3-year PFS. With a one-sided alpha of 0.05 to improve 3-year PFS from 50% to 75%, we will have 92% power by enrolling 42 pts (including 10% dropout rate) based on the binomial test. Key secondary endpoints include 1, 2, and 3-year PSA recurrence rates with testosterone recovery, PSA PFS, PSA nadir, time to testosterone recovery, and safety of combination therapy. Quality of life will be assessed by EPIC questionnaire. As of February 2019, we have enrolled and treated 12 pts in this PCCTC trial. Accrual to the STARTAR trial is ongoing (NCT03311555). Clinical trial information: NCT03311555.
Cognitive effects of androgen receptor (AR) directed therapies for advanced cancer of the prostate (COGCaP).
Authors: Van Julie , Penson David F. , Rademaker Alfred , Jackson James C. , Moses Kelvin A. , Morgans Alicia K. 
Published: May 2019

TPS5098 Background: Androgen deprivation therapy (ADT) is the cornerstone of treatment for prostate cancer (CaP). However, the relationship between ADT and the development of cognitive dysfunction in men with CaP is controversial. Past studies had various methodological limitations, including the inconsistency and insensitivity of measures used for cognitive testing. Methods: COGCaP is a multi-site, prospective observational study of cognitive function and patient reported outcomes in men with CaP treated with ADT and androgen receptor (AR) directed therapies such as enzalutamide or abiraterone acetate (AA) conducted across four U.S. sites. Patients with metastatic castration-resistant or hormone sensitive CaP starting abiraterone (N=50), or non-metastatic or metastatic castration-resistant CaP starting enzalutamide (N=50) undergo cognitive and patient reported outcome assessments at baseline, 3, 6, and 12 months. The primary endpoint compares mean change in cognitive function between groups at 3 months using CANTAB, a computer-based measure of cognitive function. This design achieves a power of 80% to detect a between-group difference in mean cognitive composite score of < 1 standard deviation and a two-sided type I error rate of 0.05. Functional MRI (fMRI) images will be assessed between baseline and 3 months to assess structural and functional changes in the brain as secondary endpoints. Study patients will be incorporated into a model of genetic risk of cognitive dysfunction in order to identify populations that are especially vulnerable to cognitive change when undergoing androgen deprivation. This ongoing study will define a reproducible methodology for cognitive assessments via computer based tests that can be standardized and disseminated within multi-site trials of men with CaP. Clinical trial information: NCT03016741.
CALLA: Efficacy and safety of durvalumab with and following concurrent chemoradiotherapy (CCRT) versus CCRT alone in women with locally advanced cervical cancer: A phase III, randomized, double-blind, multicenter study.
Authors: Monk Bradley J. , Mayadev Jyoti , Nunes Ana T , Dabrowska Brown Alicja , Marcovitz Michelle , Lanasa Mark C. 
Published: May 2019

TPS5597 Background: CCRT is the standard of care for locally advanced cervical cancer. CCRT with PD-1/PD-L1 pathway blockade may promote a more immunogenic environment through increased phagocytosis, cell death, and antigen presentation, leading to enhanced immune-mediated tumor surveillance. This Phase 3, randomized, multicenter, international, double-blind, placebo-controlled study is designed to determine the efficacy and safety of durvalumab with and following CCRT vs. CCRT alone in women with locally advanced cervical cancer (NCT03830866). Methods: The study will enroll immunotherapy-naïve adult patients (pts) with histologically confirmed cervical adenocarcinoma or cervical squamous or adenosquamous carcinoma (FIGO Stages IB2-IIB with node [N] positive and IIIA-IVA with any N) and no prior definitive surgical, radiation, or systemic therapy for cervical cancer. Approximately 714 pts will be randomized 1:1 to receive either durvalumab (1500 mg intravenously [IV]) or placebo every 4 weeks for 96 weeks. All pts will receive CCRT to the pelvis or pelvis + para-aortic radiotherapy field (45 Gy), followed by image-guided brachytherapy with cisplatin (40 mg/m2) IV or carboplatin (AUC2) IV once weekly for 5 weeks (6th dose optional). Randomization will be stratified by disease stage (FIGO Stage < III and N positive, FIGO Stage ≥III and N negative, or FIGO Stage ≥III and N positive) and region (US, Canada, EU, South Korea, and Japan vs. rest of the world). The primary endpoint is progression-free survival (assessed by investigator per RECIST v1.1 or histopathologic confirmation of local tumor progression). Secondary endpoints are overall survival, objective response and complete response (CR) rates, duration of response in pts with CR, incidence of local or distant disease progression or secondary malignancy, disease-related symptoms, and health-related quality of life (EORTC QLQ-C30 and EORTC QLQ-CX24). Pharmacokinetics, immunogenicity, and safety of durvalumab will also be assessed. Pt enrollment is ongoing. Clinical trial information: NCT03830866.
AGO-OVAR 2.29 (ENGOT-ov34): Atezolizumab in combination with bevacizumab and chemotherapy versus bevacizumab and chemotherapy in recurrent ovarian cancer (ROC).
Authors: Marme Frederik , Pautier Patricia , Van Nieuwenhuysen Els , Reuss Alexander , Redondo Andres , Lindemann Kristina , Kurzeder Christian , Marth Christian , Burges Alexander , Pietzner Klaus , Wimberger Pauline , De Gregorio Nikolaus , Harter Philipp 
Published: May 2019

TPS5601 Background: A standard non-platinum based treatment option in patients with relapsed ovarian cancer is bevacizumab in combination with paclitaxel or pegylated liposomal doxorubicin, but responses are still short-lived. Checkpoint-inhibitors as single agent have limited activity in ovarian cancer. However, the role of the checkpoint-inhibitor like atezolizumab, in addition to chemotherapy and bevacizumab in ovarian cancer is so far undefined. Methods: AGO-OVAR 2.29 is a randomized (1:1), double blinded, phase III trial evaluating the efficacy and safety of atezolizumab plus bevacizumab and chemotherapy (weekly paclitaxel or pegylated liposomal doxorubicin) compared with placebo plus bevacizumab and chemotherapy in patients with recurrent ovarian-, fallopian tube, or primary peritoneal cancer with 1st or 2nd relapse within 6 months after platinum-based chemotherapy or 3rd relapse. A tumor biopsy available at study entry for PD-L1 testing is mandatory. Patients are treated with chemotherapy plus bevacizumab +/- atezolizumab/placebo until progression or prohibitive toxicity. Co-primary endpoints are overall survival and progression-free survival. It is planned to randomize 664 patients. A safety interim analysis will be done when 24 patients have been randomized and completed at least cycle 1. As of 1st February 2019, 24 patients have been randomized. Clinical trial information: NCT03353831.
Phase Ib clinical investigation of intraperitoneal ipilimumab and nivolumab in patients with peritoneal carcinomatosis due to gynecologic malignancy.
Authors: Hinchcliff Emily , Peng Weiyi , Bayer Virginia , Haymaker Cara L. , Huang Steven Y , Sheth Rahul , Westin Shannon Neville , Lu Karen H. , Hwu Patrick , Jazaeri Amir A. 
Published: May 2019

TPS5606 Background: The peritoneal cavity is a frequent site of metastasis and recurrence for gynecologic malignancy, including approximately 80% of epithelial ovarian cancer (EOC) that presents with peritoneal involvement. These observations have led to the use of intraperitoneal (IP) route of administration for traditional cytotoxic chemotherapy. IP immunotherapy is a recognized but under explored area of clinical investigation with many potential advantages. Indeed, IP administered antibodies in both animals and human subjects are associated with absent or much lower peripheral blood concentrations. In addition to higher local and lower systemic exposure, other theoretical advantages include preferential binding to intraperitoneal and intratumoral immune cells, and absorption through the draining lymphatics of the peritoneal cavity. These pelvic and peri-aortic lymph nodes represent the most relevant lymphoid organs and as such may be the ideal site for T cell activation and trafficking back to the peritoneal tumor. Methods: The trial (NCT03508570) is a single-institution phase Ib trial to determine the recommended phase II dosing (RP2D) of IP administration of nivolumab in combination with ipilimumab. For the purpose of dose finding, the assessment period for dose limiting toxicity (DLT) is 12 weeks. The trial starts with a safety lead-in to confirm the safety of IP nivolumab before combining it with ipilimumab. A maximum sample size of 12 will be used to find the RP2D for nivolumab, up to 24 patients for the combination, and a planned expansion will be carried out such that at least 12 EOC patients are treated at RP2D of the intraperitoneal combination strategy. The secondary objectives are to describe the pharmacokinetics and toxicities, and to estimate the clinical benefit rate for the expansion cohort. Translational objectives include description of immunologic and biologic changes in serial blood and IP fluid collections as well as pre and on-treatment biopsies. Eligibility criteria include recurrent or progressive biopsy-confirmed platinum resistant EOC or other gynecologic cancer with measurable peritoneal disease, and no exposure to prior treatment with checkpoint inhibition. Enrollment began in January of 2019 with 3 subjects enrolled to date. Accrual update will be provided at the annual meeting. Clinical trial information: NCT03508570.
KEYNOTE-689: Phase 3 study of adjuvant and neoadjuvant pembrolizumab combined with standard of care (SOC) in patients with resectable, locally advanced head and neck squamous cell carcinoma.
Authors: Uppaluri Ravindra , Lee Nancy Y. , Westra William , Cohen Ezra E.W. , Haddad Robert I. , Temam Stephane , Le Tourneau Christophe , Chernock Rebecca , Safina Sufia , Klochikhin Arkadiy , Meirovitz Amichay , Braña Irene , Ge Joy Yang , Swaby Ramona F. , Bidadi Behzad , Adkins Douglas 
Published: May 2019

TPS6090 Background: Evidence of efficacy and pathological response at the time of surgery was reported in two phase 2 studies (NCT02296684 and NCT02641093) of preoperative pembrolizumab in patients with high-risk, resectable, locally advanced (LA) head and neck squamous cell carcinoma (HNSCC). The randomized, open-label, phase 3 KEYNOTE-689 trial ( NCT03765918) will evaluate efficacy and safety of pembrolizumab as neoadjuvant and adjuvant therapy in combination with SOC (radiotherapy ± cisplatin) in patients with previously untreated, resectable LA HNSCC. Methods: Patients with newly diagnosed LA HNSCC will be randomly assigned 1:1 to two treatment arms. Patients in arm A will receive neoadjuvant pembrolizumab (200 mg Q3W for two cycles) followed by surgical resection then SOC plus adjuvant pembrolizumab (15 cycles). Patients in arm B will undergo only surgical resection followed by adjuvant SOC. Eligibility criteria will include age ≥18 years; newly diagnosed, resectable, stage III/IVA HNSCC (AJCC Cancer Staging Manual, 8th edition); and ECOG performance status 0-1. Randomization will be stratified by primary tumor site (oropharynx/oral cavity vs larynx vs hypopharynx), tumor stage (III vs IVA), and HPV p16 status (oropharynx p16 positive vs oropharynx p16 negative or larynx/hypopharynx/oral cavity). Treatment will continue until disease progression, unacceptable toxicity, or decision to withdraw. Patients in arm A will undergo the first radiologic imaging assessment after two cycles of neoadjuvant pembrolizumab and before surgery. In both arms, postoperative imaging will be performed 12 weeks after SOC, then every 3 months until the end of year 3, and then every 6 months until the end of year 5. Dual primary end points are major pathological response, defined as ≤10% invasive squamous cell carcinoma within resected primary tumor and sampled regional lymph nodes per blinded central pathology, and event-free survival. Secondary end points include overall survival, pathological complete response, and safety and tolerability. Recruitment is ongoing and will continue until ~600 patients are enrolled. Clinical trial information: NCT03765918.
Comparative effectiveness trial of transoral head and neck surgery followed by adjuvant radio(chemo)therapy versus primary radiochemotherapy for oropharyngeal cancer (TopROC).
Authors: Busch Chia-Jung , Laban Simon , Wittekindt Claus , Stromberger Carmen , Tribius Silke , Betz Christian Stephan , Klußmann Jens Peter , Budach Volker , Muenscher Adrian 
Published: May 2019

TPS6093 Background: For locally advanced, transorally resectable oropharyngeal cancer (OPSCC), both, surgical resection and risk-adapted adjuvant (chemo)radiotherapy or definite chemoradiotherapy with or without salvage surgery are considered the current standard of care. To date, these two different therapeutic approaches for transorally resectable OPSCC have not been compared head to head in a randomized trial yet. The goal of this study is to compare primary transoral surgery followed by adjuvant treatment with definitive chemoradiation for resectable OPSCC, especially with regards to loco-regional control as well as organ function. Methods: TopROC is a prospective, two-arm, open label, multicenter, randomized controlled comparative effectiveness study. Eligible pts. are ≥18 years old with treatment-naïve, histologically proven OPSCC (T1, N2a-c, M0; T2, N1-2c, M0; T3, N0-2c, M0 TNM 7th ed.) which are amenable to transoral resection, ECOG PS ≤2 and no distant metastasis. p16 immunohistochemistry by local pathology or FFPE tissue must be available for central diagnostic. 280 pts. will be randomly assigned (1:1) to surgical treatment (arm A) or chemoradiation (arm B). Standard of care treatment will be done according to daily clinical practice. Arm A consists of transoral surgical resection with neck dissection followed by risk-adapted adjuvant (chemo)radiation. Pts. treated in arm B receive standard chemoradiation, residual tumor may be subject to salvage surgery. Follow-up visits are planned until three years after treatment. Primary endpoint is time to local or locoregional failure or death from any cause (LRF). Secondary endpoints include overall and disease-free survival, toxicity, patient reported outcomes and cost-effectiveness analysis. Approximately 20 centers will be involved in Germany. This trial is supported by the German Cancer Aid and accompanied by a large scientific support program. Recruitment started in January 2018. Clinical trial information: NCT03691441.
Roman: Reduction in oral mucositis with avasopasem manganese (GC4419)—Phase 3 trial in patients receiving chemoradiotherapy for locally-advanced, non-metastatic head and neck cancer.
Authors: Holmlund Jon , Brill Jeffrey Mark , Lee Christopher M. , Saunders Deborah , Sonis Stephen T. , Downs Matt , Anderson Carryn M. 
Published: May 2019

TPS6096 Background: Approximately 70% of patients receiving intensity-modulated radiotherapy (IMRT) plus cisplatin for locally advanced head and neck cancer (HNC) develop SOM, defined as WHO Grade 3 or 4, which limits patients' ability to eat solids (Gr 3) or liquids (Gr 4, requiring enteral nutrition). An RT-induced burst of superoxide initiates oral mucositis (OM) development. GC4419, a superoxide dismutase mimetic, interrupts this process by converting superoxide to H2O2. It showed promising reduction of SOM in a published open-label Phase 1b/2a trial (IJROBP 1 Feb 2018). In a subsequent randomized, double-blind placebo-controlled trial in 223 patients receiving IMRT/cisplatin for HNC (ASCO 2018), 90 mg of GC4419 administered M-F prior to IMRT demonstrated statistically significant reduction in SOM duration (p=0.024, median 1.5 days @ 90 mg vs 19 days placebo) and meaningful reductions @ 90 mg in SOM incidence (43% vs 65%) and severity (incidence of Grade 4, 16% vs 30%). The safety profile was acceptable and consistent with the known toxicities of IMRT/cisplatin. Methods: 335 patients at multiple centers in the U.S. and Canada with locally-advanced, nonmetastatic head and neck cancer (oral cavity/oropharyngeal) receiving 70 Gy IMRT (>50 Gy to > 2 oral sites) plus cisplatin (40 mg/m2 qwk x 6-7, or 100 mg/m2 q3wk x 3) are being randomized (double-blinded) 3:2 to 90 mg of GC4419 or placebo, M-F before each RT fraction. Enrollment is stratified by cisplatin schedule and treatment setting (definitive vs post-op). OM by the WHO scale will be assessed twice weekly during RT & weekly for 2 weeks post RT. The primary efficacy endpoint is incidence of SOM through the end of IMRT. Secondary efficacy endpoints include severity (incidence of Grade 4 OM through the end of IMRT), & days of SOM (days from first to last SOM for all patients, with patients never developing SOM having 0 days of SOM by definition). Days of SOM for the subset developing SOM will be analyzed descriptively. Patients will be followed for one year post IMRT for tumor progression/recurrence and for two years for survival. Supported by Galera Therapeutics, Inc. Clinical trial information: NCT03689712.