bluuebunny/crossref_metadata_2025_split huggingface dataset:
PEARLY: A randomized, multicenter, open-label, phase III trial comparing anthracyclines followed by taxane versus anthracyclines followed by taxane plus carboplatin as (neo)adjuvant therapy in patients with early triple-negative breast cancer.
Authors: Kim Gun Min , Jeung Hei-Cheul , Jung Kyung Hae , Kim Se Hyun , Kim Han Jo , Lee Ki Hyeong , Park Kyong Hwa , Lee Ji Eun , Ahn Mi Sun , Kohn Sujin , Lee Sung Sook , Moon Yong Wha , Sohn Joohyuk 
Published: September 2018

TPS587 Background: Triple-negative breast cancer (TNBC) is an aggressive tumor with poor prognosis. There are no molecular targets for TNBC, and there is an unmet need to provide new drugs to patients with TNBC. Platinum agents are known to have an anti-tumor activity in TNBC, especially in BRCA-mutated tumor. Addition of carboplatin significantly increased pathologic complete response rates with neoadjuvant chemotherapy in recent randomized studies. There are no data about adjuvant role of carboplatin for TNBC in a randomized trial. Methods: PEARLY is a randomized, multicenter, open-label, phase III trial comparing anthracyclines followed by taxane versus anthracyclines followed by taxane plus carboplatin as (neo)adjuvant therapy in patients with triple-negative breast cancer (TNBC). Patients with stage II or III TNBC who need adjuvant or neoadjuvant chemotherapy were included. Any prior systemic therapy for breast cancer was not allowed. Bilateral, metastatic, and inflammatory breast cancer are excluded. A total of 840 patients will be enrolled for 3 years. Patients were randomized 1:1, stratified based on the node positivity (N0 vs N+), institution, treatment setting (neoadjuvant vs. adjuvant), and BRCA mutation status (positive vs. negative). Standard arm treatment consists of doxorubicin 60 mg/m2 IV + cyclophosphamide 600 mg/m2 IV every 3 weeks for 4 cycles followed by taxane treatment (paclitaxel 80 mg/m2 IV weekly for 12 doses or docetaxel 75mg/m2 IV every 3 weeks for 4 cycles). Experimental arm added carboplatin AUC5 IV every 3 weeks for 4 cycles during taxane treatment. The primary objective was to evaluate 5-year event free survival (EFS) rate. Secondary objectives included overall survival, distant recurrence free survival, pathologic complete response, and tolerability. The analysis is planned at 248 EFS events, which provides approximately 80% power to detect superiority of standard treatment plus carboplatin versus standard treatment using a log-rank test, assuming a hazard ratio of 0.7 at a two sided alpha of 0.05. Data is expected in 2023. Clinical trial information: NCT02441933.
NRG Oncology/NSABP B-51/RTOG 1304: Phase III trial to determine if chest wall and regional nodal radiotherapy (CWRNRT) post mastectomy (Mx) or the addition of RNRT to breast RT post breast-conserving surgery (BCS) reduces invasive breast cancer recurrence free interval (IBCRFI) in patients (pts) with positive axillary (PAx) nodes who are ypN0 after neoadjuvant chemotherapy (NC).
Authors: Mamounas Eleftherios P. , Bandos Hanna , White Julia R. , Julian Thomas B. , Khan Atif J. , Shaitelman Simona Flora , Torres Mylin Ann , Vicini Frank , Ganz Patricia A. , McCloskey Susan Ann , Paik Soonmyung , Gupta Nilendu , Li X. Allen , DiCostanzo Dominic J. , Curran Walter John , Wolmark Norman 
Published: September 2018

TPS589 Background: This phase III post-NC trial evaluates if CWRNRT post-Mx or whole breast irradiation (WBI) with RNRT after BCS significantly reduces the IBCR-FI rate in pts with PAx nodes that are negative after NC. Secondary aims are OS, LRR-FI, DR-FI, DFS-DCIS, second primary cancer, and comparison of RT effect on cosmesis in reconstructed Mx pts. Correlative science examines RT effect by tumor subtype, molecular outcome predictors for residual disease pts, and predictors for the degree of reduction in locoregional recurrence. Methods: Clinical T1-3, N1 IBC PAx nodes (FNA or core needle biopsy) pts complete ≥12 weeks of NC (anthracycline and/or taxane). HER2+ pts receive anti-HER2 therapy. Following NC BCS or Mx, sentinel node biopsy (≥3 nodes) and/or Ax dissection with histologically negative nodes is performed. ER/PR and HER-2neu status before NC is required. Pts receive required systemic therapy. Radiation credentialing with a facility questionnaire/case benchmark is required. Random assignment for Mx pts is to no CWRNRT or CWRNRT and for BCS pts to WBI or WBI RNRT. Statistics: 1636 pts to be enrolled over 5 yrs (definitive analysis at 7.5 yrs). Study is powered at 80% to test that RT reduces the annual hazard rate of events for IBCR-FI by 35% for an absolute risk reduction of 4.6% (5-yr cumulative rate). Intent-to-treat analysis with 3 interim analyses (43, 86, and 129 events) and a 4th/final analysis at 172 events. Pt-reported outcomes focusing on RT effect will be provided by 736 pts before random assignment and at 3, 6, 12, and 24 mos. Accrual as of 2-2-17 is 534 (32.64%). Contacts: Questions: NRG Oncology Pgh Clin Coord Dpt: 1-800-477-7227 or ccd@nsabp.org . Support: U10 CA-2166; -180868, -180822; 189867; Elekta Clinical trial information: NCT01872975.
Phase II trial of neoadjuvant (neo) palbociclib (Palbo) plus anastrozole (ana) in endocrine resistant clinical stage 2/3 estrogen receptor positive and HER2 negative (ER+ HER2-) breast cancer (BC).
Authors: Bagegni Nusayba Ali , Gao Feng , Goetz Matthew P. , Northfelt Donald W. , Forero-Torres Andres , Anderson Jill , Vij Kiran R. , Sanati Souzan , Ellis Matthew J , Ma Cynthia X. 
Published: September 2018

TPS592 Background: Persistent cell proliferation (Ki67 > 10%) on tumor biopsies as early as 2-4 weeks (wks) on neo endocrine therapy (ET) identifies resistant tumors in ~20% patients (pts) with early stage ER+ HER2- BC who are at high risk of relapse. Palbo plus ET significantly improves progression free survival in pts with ET naïve or resistant advanced ER+ HER2- BC, and is being evaluated in the adjuvant setting. However, biomarkers predictive of palbo sensitivity are unknown. Ki67 analysis of serial tumor biopsies in the neo palbo and ana (NeoPalAna) trial demonstrated that 2 wks of palbo plus ana potently inhibited Ki67 and induced complete cell cycle arrest (CCCA, Ki67≤2.7%) in tumors with high Ki67 post 4 wks ana run-in. This study is therefore aimed to prospectively investigate the biological activity of palbo plus ana in ET resistant ER+ HER2- BC. Methods: The primary objective is to assess the rate of CCCA (central Ki67 ≤2.7%) after 2 wks of neo palbo and ana. Secondary objectives include analysis of tumor biopsies to explore response biomarkers. Key inclusions include women with clinical stage 2/3 ER+ HER2- BC, central Ki67 > 10% after ≥2 wks of any neo ET, adequate organ function. Key exclusions include prior CDK 4/6 inhibitor, treatment of BC except ET, concomitant use of strong CYP3A4 inhibitor. Pts receive palbo (125mg PO daily, days 1-21, 28-day cycle), ana (1 mg PO daily) and goserelin (if premenopausal). Pts with C1D15 Ki67 > 10% will discontinue study. If C1D15 Ki67 ≤10%, pt will receive 4 cycles of treatment, and additional 10-12 days of palbo if counts normalized within 3 wks post C4D28. Following surgery, pts are eligible for 2 years of adjuvant palbo. A sample size of 37 (stage 1, n = 12, stage 2 n = 25) by simon optimal two stage phase II design will be employed to assess whether the rate of CCCA is ≤5% vs ≥20% (90% power, alpha 0.1). Stage 2 will proceed if ≥1 had CCCA in stage 1. If ≤3 of 37 had CCCA, this regimen will be considered ineffective. The study is active and has enrolled 4 pts. Clinical trial information: NCT01723774.
Phase III randomised controlled trial (RCT) comparing alternative regimens for escalating treatment of intermediate and high-risk oropharyngeal cancer (CompARE).
Authors: Mehanna Hisham Mohamed , Sen Mehmet , Chester John David , Sanghera Paul , Paleri Vinidh , Gaunt Piers , Babrah Jaspreet , Hartley Andrew G. J. , Kong Anthony , Al-Booz H , Foran Bernadette , Miles Elizabeth , Robinson Max , Jepson Marcus , Donnovan Jenny , Yap Christina , Firth Charlotte , Gaunt Claire , Bowden Sarah Jane , Forster Martin David 
Published: September 2018

TPS6091 Background: Patients with intermediate and high-risk oropharyngeal cancer (OPC) have poorer response to standard treatment and poorer overall survival compared to low-risk OPC. The CompARE trial is designed to test alternative approaches to intensification of treatment for these patients to improve survival. Methods: CompARE is a pragmatic phase III open-label multicenter RCT with an adaptive multi-arm multi-stage design. Eligible OPC patients include those with; HPV negative, T1-T4, N1-N3 or T3-4, N0 or HPV positive current smokers (or ≥ 10 pack years previous smoking history) with T1-T4, N2b-N3. The primary outcome measure is overall survival. Secondary outcome measures include quality of life, toxicity, swallowing outcomes, feeding tube incidence, surgical complications and cost-effectiveness. The trial is powered to detect a hazard ratio of 0.69 (an improvement of 10% in OS at 3-years) requiring 128 control events. It is estimated that the study will take 6.5 years to recruit sufficient patients to experience the number of events needed. Planned interim futility analyses using event-free survival (EFS) will be performed when 70 and 114 control EFS events have occurred. Current treatment arms are; (1) control: standard treatment of 3-weekly cisplatin 100mg/m2 or weekly 40mg/m2 with Intensity Modulated Radiotherapy (IMRT) using 70Gy in 35F +/- neck dissection determined by clinical and radiological assessment 3-months post treatment. (3) IMRT 64Gy in 25F + cisplatin 100mg/m2 day 1 of week 1 and week 5 or weekly 40mg/m2+/- neck dissection as per standard treatment. (4) Resection of primary + selective neck dissection followed by standard treatment. (5) One cycle of induction durvalumab 1500mg followed by standard treatment then durvalumab 1500mg every four weeks for a total of 6 months. Recruitment to arm (2) involving induction chemotherapy from the original protocol is suspended. Since July 2015, 42 patients have been randomised with 16 sites open to recruitment. The Data Monitoring Committee last reviewed progress and conduct of the trial in September 2016 and recommended continuation. ISRCTN Number: 41478539, CRUK CRUK/13/026 Clinical trial information: 41478539.
An open-label, single-arm, multi-institutional phase II trial of avelumab for recurrent, metastatic nasopharyngeal carcinoma.
Authors: Sacco Assuntina Gesualda , Messer Karen , Leidner Rom S. , Colevas A. Dimitrios , Nieva Jorge J. , Chau Nicole Grace , Nangia Chaitali Singh , Pinsky Benjamin , Gold Kathryn A. , Daniels Gregory A. , Cohen Ezra E.W. 
Published: September 2018

TPS6092 Background: The majority of patients with nasopharyngeal carcinoma (NPC) present with locally advanced disease, with a predilection for early systemic dissemination. For patients who develop recurrent and/or metastatic (R/M) NPC, survival is poor. Following first-line platinum-based regimens, there is no well-defined paradigm for subsequent therapies. Inhibition of PD-L1 with Avelumab is an attractive strategy because Epstein-Barr virus (EBV), the primary causative agent in NPC pathogenesis, universally upregulates PD-L1 expression; proposed mechanisms of upregulation include immune resistance via innate (EBV-induced latent membrane protein-1) and adaptive (Interferon-gamma) mechanisms; increased PD-L1 expression is an independent poor prognostic factor for disease-free survival. Methods: Patients with histologically/cytologically confirmed, EBV-related NPC not amenable to curative intent therapy who received ≥1 prior line of systemic therapy for R/M disease are eligible. Patients must be at least 18 years old, ECOG 0-2, willing to undergo tumor biopsy, have adequate organ and marrow function, and no prior therapy with PD-1/PD-L1 inhibitors. 39 patients will be enrolled across 6 sites. Patients will receive Avelumab 10 mg/kg IV on days 1 and 15 of each 28-day cycle. Treatment will continue until disease progression, unacceptable toxicity, investigator/patient decision. A newly obtained tumor specimen is required at enrollment; optional biopsy at time of progression. EBV plasma DNA titers will be evaluated at baseline, during treatment and at progression, using an EBV BamHI-W DNA PCR. Blood samples at baseline and 12 weeks after treatment initiation will be obtained for correlatives. Primary endpoint is overall response rate (ORR; complete and partial responses) at 6 months per RECIST. A two-stage design will reject H0 (ORR 15%) if the observed ORR is ≥30%, α 0.1, β 0.8, required sample size n = 39. Secondary endpoints include duration of response, progression-free and overall survival. Correlative analyses will evaluate PD-L1 expression, T and B-cell subsets, frequency and clonality. The study has accrued 2 of planned 39 patients. NCT02875613. Clinical trial information: NCT02875613.
Phase ιι (window) preoperative study of olaparib with cisplatin or with durvalumab or alone or no treatment in patients with histologically proven head and neck squamous cell carcinoma who are candidates for surgery (OPHELIA).
Authors: Psyrri Amanda , Papaxoinis George , Economopoulou Panagiota , Kotsantis Ioannis , Kotoula Vassiliki , Tsavaris Onoufrios , Avgerinou Chrysanthi , Fountzilas George 
Published: September 2018

TPS6096 Background: Novel agents are often investigated in unselected end-stage cancer patients and their efficacy is evaluated by the classical RECIST criteria making unlikely to fully exploit the antitumor potential of these targeted agents. Olaparib (O) is a potent inhibitor of PARP especially active in tumors that have homologous recombination DNA repair pathway deficiencies. Durvalumab (D) is a selective, high-affinity human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80, overcoming PD-L1-mediated inhibition of T-cell activation. There is substantial evidence that tumor cells use PARP to repair platinum-induced DNA damage and thus escape apoptosis. In addition, O may complement the antitumor activity of D by increasing DNA damage through repair inhibition. Methods: OPHELIA is an open-label randomized multicenter phase II (window) trial in patients (pts) with head and neck squamous cell carcinoma (HNSCC). Treatment-naive HNSCC pts selected for primary curative study are randomized 3:3:3:1 in 4 neoadjuvant treatment groups: D 1500 mg on day 1 followed by O 600mg daily for 21-28 days (12 pts), cisplatin 60 mg/m2 on day 1 followed by O 75mg daily for 5 days (12 pts), monotherapy with O 600mg daily for 21-28 days (12 pts) and no treatment (5 pts). Preoperative therapy is discontinued 24 to 36 hours before surgery. Tumor biopsies, CT scans, PET and blood specimens are obtained at diagnosis and at surgery. Primary endpoint is the change in the tumor Ki-67 before and after treatment. Secondary endpoints are objective response rate according to RECIST 1.1 criteria, pathologic complete response rate and metabolic response rate assessed by FDG-PET/CT scan. Exploratory endpoints will include tumor and blood biomarkers. Translational correlates will be tested in tumor tissue, plasma and germline DNA and will include mutations in genes associated with DNA repair assessed by next generation sequencing and circulating tumor cells (CTCs) evaluated for DNA repair biomarkers and PD-L1. Trial is open to enrollment. Clinical trial information: NCT02882308.
A phase II study of pembrolizumab and docetaxel for aggressive RAI refractory thyroid carcinomas or salivary gland cancers: The iPRIME study.
Authors: Seiwert Tanguy Y. , De Souza Jonas A. , Vokes Everett E. , Agrawal Nishant 
Published: September 2018

TPS6099 Background: Both aggressive, radioactive iodine refractory thyroid cancers as well as high-grade salivary gland cancers respond poorly to chemotherapy, and there is no widely used standard of care. Targeted thearpies as well as cytotoxic chemotherapy (e.g. doxorubicin, or taxanes) are commonly used, but are only modestly effective. Both salivary gland and thyroid cancers have been shown to have tumor infiltrating lymphocytes, tumor inflammation, and PD-L1 expression ( Ayers, AACR 2015). Early data with anti-PD-1 immunotherapy using pembrolizumab (Keynote 28) show activity in ≤10a% of patients in a biomarker selected population (Keynote 28 thyroid and salivary gland cohorts). However, most patients are not PD-L1 positive and were not eligible. Recently synergy of anti-PD-1 checkpoint blockade with cytotoxic chemotherapy was reported in several studies (e.g. Langer et al, Keynote 21G) . Mechanistically chemotherapy may increase tumor inflammation, and eradicate immusupressive myeloid derived suppressor cells (MDSCs). Data suggest a significant increase in the response rate e. g. in KN21G from 29% to 55%. Furthermore the depths of responses and durability improve, including patients with PD-L1 negative tumors. Methods: We hypothesize that the combination of PD-1 checkpoint blockade and cytotoxic chemotherapy will show synergistic activity in aggressive thyroid cancers and salivary gland cancers. Eligible patients will have radioactive iodine refractory, aggressive thyroid cancer (cohort A, N = 25 pts), or progressive salivary gland cancers (cohort B, N = 25 pts). There will be no PD-L1 or other biomarker selection. Patients must have progressed on prior therapy. Patients will receive docetaxel at a dose of 75mg/m2 Q21 days as well as pembrolizumab 200mg flat-dose Q21 days intravenously. The primary outcome of this study is response rate. The addition of pembrolizumab to chemotherapy will increase the response rate from 20% (H0) to 40% (H1). A simon two-stage design will be used for each cohort (cohorts A and B) with an estimate 81% power in each arm. Patient screening and enrollment are expected to begin mid 2017. Clinical trial information: pending.
Objective assessment of physical activity during chemotherapy for breast cancer.
Authors: Melisko Michelle E. , Hadeler Edward Kenji , Nelson Sandahl H , Lunde Audrey , Acerbi Irene , Rugo Hope S. , Majure Melanie Catherine , Chien Amy Jo , Esserman Laura , Hartman Sheri J. 
Published: September 2018

TPS6626 Background: Exercise can alleviate side effects of chemotherapy, improve quality of life (QOL), and positively impact disease specific and overall survival. Despite the benefits of physical activity (PA), many patients’ activity levels decrease during chemotherapy. Wearable devices, such as the Fitbit, can provide insight into patterns of activity, and help encourage behavior change. The aims of this study are: 1) determine the feasibility/acceptability of using a Fitbit to measure PA and sleep throughout chemotherapy for breast cancer; 2) describe patterns of PA, sedentary time, and sleep during chemotherapy; 3) explore associations of activity and sleep with QOL. Methods: Non-metastatic breast cancer patients from UCSF and UCSD will be enrolled prior to starting chemotherapy. Eligibility criteria include ability to speak/read English, walk unassisted, and access to internet or Fitbit compatible smart phone. Patients sign informed consent, receive a Fitbit Charge HR and guidance on how to use the device. Patients are instructed to wear the Fitbit throughout their adjuvant or neoadjuvant chemotherapy and 6 months post therapy and to sync the Fitbit at least weekly. Patients complete surveys at start, midpoint, end, and 6 months post chemotherapy. Questionnaires include PROMIS anxiety, depression, physical function, fatigue, cognitive function, social roles, comfort with technology and usefulness of the Fitbit. Fitabase database collects minute level activity, sleep, and heart rate. To assess feasibility, we will evaluate if a participant wears FitBit for at least 10 hour per day for ≥ 80% of the days during chemotherapy. We will use mixed effects regression models to assess patterns of PA and associations between activity and QOL. All models will include activity time and Fitbit wear time and will control for the potential confounding effects of age and other demographic or clinical variables. As of February 6 2017, 48 out of a planned 80 patients are enrolled. Acknowledgment: Athena Breast Health Network investigators and patients; support at UCSD by NCI (U54 CA155435-01) and by gift from Carol Vassiliadis and family; NCI grant K07CA181323 to SH; UCSF M Zion Health Fund Award, GBCTB unrestricted funding and TriValley SOCKS to MM. Clinical trial information: NCT03041545.
COSMOS: MOR208 plus idelalisib or venetoclax in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) previously treated with a Bruton's tyrosine kinase inhibitor (BTKi)—A two-cohort phase II study.
Authors: Wendtner Clemens-Martin , Byrd John C. , Foà Robin , Greil Richard , Hillmen Peter , Jäger Ulrich , Jurczak Wojciech , Kelemen Peter , Laribi Kamel , Munir Talha , Schetelig Johannes , Staber Philipp B. , Stilgenbauer Stephan , Woyach Jennifer Ann 
Published: September 2018

TPS7567 Background: Patients (pts) with R/R CLL who discontinue treatment with the BTKi ibrutinib due to progression have a particularly dismal prognosis. A phase I study showed that the Fc-enhanced, humanized, CD19 antibody MOR208 was well tolerated with encouraging single-agent activity in pts with R/R CLL/SLL. In preclinical models, MOR208 showed synergy with idelalisib (an inhibitor of PI3K delta) and venetoclax (an inhibitor of BCL-2), both approved for the treatment of CLL. Methods: This two-cohort, phase II study will investigate MOR208 combined with idelalisib (cohort A) or venetoclax (cohort B) in pts with R/R CLL or R/R SLL and includes a safety run-in phase for each cohort, to be evaluated by an Independent Data Monitoring Committee. Key inclusion criteria: aged ≥18 years, R/R CLL/SLL while receiving a BTKi therapy or intolerance of such therapy, BTKi administered as a single-agent or in combination for at least 1 month as the most recent prior anticancer therapy, ECOG performance status of 0–2, and adequate organ function. Key exclusion criteria: transformed CLL/SLL or Richter’s syndrome, BTKi treatment within 5 days prior to study drug dosing, prior treatment with a CD19-targeted therapy, a PI3K inhibitor (cohort A) or a BCL-2 inhibitor (cohort B). Pts will be treated for a maximum of 24 (28-day) cycles or until disease progression. Treatment will be MOR208 12 mg/kg IV (weekly for the first 3 months, every second week for the next 3 months, and monthly thereafter) in combination with oral idelalisib 150 mg twice-daily or venetoclax administered on a weekly ramp-up dosing schedule to the recommended daily dose of 400 mg. Primary endpoint: overall response rate based on independent review; secondary and exploratory endpoints include: progression-free and overall survival, duration of response, safety, pharmacokinetics, MOR208 immunogenicity, quality of life and minimal residual disease negativity. 120 pts per cohort are planned. Clinical trial information: 2015-002915-14.