bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trial in progress: A phase III, randomized, open-label study comparing zanubrutinib plus rituximab versus bendamustine plus rituximab in patients with previously untreated mantle cell lymphoma (MCL).
Authors: Dreyling Martin H. , Tam Constantine Si Lun , Wang Michael , Smith Stephen Douglas , Ladetto Marco , Huang Huiqiang , Elstrom Rebecca L. , Co Melannie , Holmgren Eric , Huang Jane , Le Gouill Steven 
Published: May 2020

TPS8071 Background: Bruton tyrosine kinase (BTK) mediates B-cell proliferation, migration, and adhesion. BTK inhibition has emerged as a strategy for targeting B-cell malignancies, including MCL. Zanubrutinib is a next-generation BTK inhibitor that was designed to maximize BTK occupancy and minimize off-target inhibition of TEC- and EGFR-family kinases, with favorable pharmacokinetic and pharmacodynamic properties. Zanubrutinib monotherapy has been evaluated in 118 patients (pts) with relapsed/refractory MCL in 2 single-arm studies: BGB-3111-206 [NCT03206970] and BGB-3111-AU-003 [NCT02343120]. The overall response rate (ORR) by independent review committee (IRC) in both trials was 84% with median durations of response of 19.5 and 18.5 months, respectively. First-line treatment for MCL has failed to cure most pts, particularly elderly or transplant-ineligible groups, and chemotherapy-based approaches result in cumulative, long-term risks. The study described herein is designed to evaluate the safety and efficacy of zanubrutinib plus rituximab versus bendamustine plus rituximab in elderly pts and pts with comorbidities with previously untreated MCL who are ineligible for stem cell transplant. Methods: This ongoing phase 3, open-label study will enroll ≈500 pts to be randomized 1:1, stratified by MCL International Prognostic Index score (low vs intermediate/high), age ( < 70 vs ≥70 years), and geographic region (North America/Europe vs Asia-Pacific). In arm A, pts will receive up to six 28-day cycles of oral zanubrutinib 160 mg twice daily in combination with intravenous (IV) rituximab 375 mg/m2 on day 1 of each cycle. After 6 cycles, zanubrutinib will continue as a monotherapy until progressive disease, unacceptable toxicity, or withdrawal of consent. In arm B, pts will receive up to six 28-day cycles of IV bendamustine 90 mg/m2 on days 1 and 2 of each cycle and rituximab 375 mg/m2 on day 1 of each cycle, followed by observation. Eligible pts must have histologically confirmed MCL and be aged ≥70 years, or 65-69 years with defined comorbidities. Disease response will be assessed per the 2014 Lugano Classification for non-Hodgkin lymphoma. The primary endpoint is progression-free survival (PFS) determined by IRC. Key secondary end points include PFS by investigator assessment, ORR, time to and duration of response, overall survival, and safety. Recruitment is ongoing. Clinical trial information: NCT04002297 .
Subcutaneous daratumumab in patients with multiple myeloma who have been previously treated with intravenous daratumumab: A multicenter, randomized, phase II study (LYNX).
Authors: Bahlis Nizar J. , Zonder Jeffrey A. , Wroblewski Susan , Qi Ming , Renaud Thomas , Jackson Carolyn Chang , Facon Thierry 
Published: May 2020

TPS8553 Background: The intravenous (IV) formulation of daratumumab (DARA), a human CD38-targeted monoclonal antibody, is approved in many countries for use as monotherapy in relapsed/refractory multiple myeloma (RRMM) and in combination with standard-of-care regimens in RRMM or newly diagnosed MM. A subcutaneous (SC) formulation of DARA is under investigation in several ongoing studies. In the phase 3 COLUMBA study, DARA SC was shown to be non-inferior to DARA IV, demonstrating similar efficacy and pharmacokinetics, with a significantly decreased rate of infusion-related reactions and reduced administration time. The phase 2 LYNX (MMY2065) study will evaluate the efficacy and safety of retreatment with DARA. Methods: In this ongoing, multicenter, open-label, randomized phase 2 study, ~230 patients (pts) with prior exposure to DARA will be randomized 1:1 to receive carfilzomib and dexamethasone (Kd) ± DARA. Pts must have received 1 to 2 prior lines of therapy (at least one of which included DARA IV), with DARA-based therapy completed ≥3 months prior to randomization. Eligible pts have achieved a partial response or better (IMWG criteria) to DARA-based therapy, with a duration of response of ≥4 months. Pts must not have discontinued DARA due to a related adverse event or received prior treatment with carfilzomib. Pts will receive 20 mg/m2 carfilzomib IV on Day 1 of Cycle 1, escalated to 70 mg/m2 on Days 8 and 15; carfilzomib 70 mg/m2 will be administered on Days 1, 8, and 15 of each 28-day cycle thereafter. Dexamethasone 40 mg will be administered (IV or PO) QW for Cycles 1-9 and then on Days 1, 8 and 15 from Cycle 10 onwards. Pts in the D-Kd group will also receive DARA SC (1,800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; Halozyme]) QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W thereafter. The primary endpoint is the rate of pts achieving a very good partial response or better. Secondary endpoints include overall response rate, rate of pts achieving complete response or better, progression-free survival, overall survival, overall minimal residual disease-negativity rate, time to next treatment, pharmacokinetics, and safety. Clinical trial information: NCT03871829 .
ALCHEMIST: Adjuvant targeted therapy or immunotherapy for high-risk resected NSCLC.
Authors: Sands Jacob , Mandrekar Sumithra J. , Oxnard Geoffrey R. , Kozono David E. , Hillman Shauna L , Dahlberg Suzanne Eleanor , Sun Zhuoxin , Chaft Jamie E. , Govindan Ramaswamy , Gerber David E. , Gray Jhanelle Elaine , Malik Shakun M. , Mooney Margaret M. , Janne Pasi A. , Vokes Everett E. , Kelly Karen , Ramalingam Suresh S. , Stinchcombe Tom 
Published: May 2020

TPS9077 Background: ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial) is a clinical trial platform of the National Cancer Institute that offers biomarker analysis for high-risk resected non-small cell lung cancer (NSCLC) to support randomized trials of novel adjuvant therapies within the National Clinical Trials Network (NCTN). EA5142, a trial of adjuvant nivolumab for patients (pts) without EGFR / ALK alterations, has completed enrollment. Given the survival benefit seen with 1st-line chemo-immunotherapy (chemo-IO) for advanced NSCLC without EGFR / ALK alterations, there was compelling rationale for the launch of a trial offering concurrent immunotherapy with adjuvant chemo. Here we report updated enrollment to ALCHEMIST as of Jan 14, 2020. Methods: ALCHEMIST includes a screening trial (A151216, 5362 registered) that enrolls pts with completely resected clinical stage IB (≥4 cm)–IIIA (per AJCC 7) NSCLC. Tissue and blood are collected, biomarker testing includes EGFR sequencing, ALK FISH and PD-L1 IHC. 733 active sites are enrolling across the NCTN. Pts with EGFR mutations may enroll to adjuvant erlotinib vs observation (A081105, 352 randomized); those with ALK fusions may enroll to adjuvant crizotinib vs observation (E4512, 99 randomized). A trial offering adjuvant nivolumab vs observation regardless of PD-L1 status (EA5142, 935 randomized) recently completed enrollment. To support ongoing investigation of adjuvant immunotherapy, ALCHEMIST is adding A081801 (opens spring 2020). Pts will be randomized to one of 3 arms: chemo-IO with pembrolizumab during and after chemo vs sequential chemo followed by pembrolizumab vs chemo alone. Pts with pathological N2 nodes are eligible and can undergo postoperative radiotherapy after completing chemo. Pts are eligible if enrolled to A151216, negative for EGFR and ALK alterations, and with PD-L1 testing completed (required for stratification). Local testing for EGFR, ALK and PD-L1 will be accepted for enrollment; central testing will not delay randomization. Pts may not have received any therapy except surgery for the lung cancer and must be age >18, Eastern Cooperative Oncology Group performance status 0-1, have no active autoimmune disease requiring systemic treatment within 2 years, must not be pregnant or nursing, have no active second malignancy within 3 years and meet standard organ function values. By building off the ongoing ALCHEMIST platform, we hope to facilitate rapid enrollment to A081801 across participating NCTN sites. Clinical trial information: NCT02194738.
A phase III randomized trial of pleurectomy/decortication plus chemotherapy with or without adjuvant hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) for malignant pleural mesothelioma (MPM) (NRG LU-006).
Authors: Rimner Andreas , Zauderer Marjorie Glass , Yorke Ellen , Simone Charles B. , Gill Ritu R. , Voong K Ranh , Peikert Tobias , Tsao Ming Sound , Li Zuofeng , Rusch Valerie W. , Bradley Jeffrey 
Published: May 2020

TPS9079 Background: Pleurectomy/Decortication (P/D) with neoadjuvant or adjuvant chemotherapy has become a common lung-sparing surgical approach for MPM. Adjuvant hemithoracic IMPRINT was developed at Memorial Sloan Kettering Cancer Center and safe in a multi-institutional phase II study, with promising survival outcomes. The National Cancer Institute (NCI) sponsored this phase III randomized cooperative group trial to test the efficacy of this lung-sparing trimodality approach for resectable MPM. Methods: Patients with newly diagnosed MPM amenable to P/D are enrolled and undergo P/D followed by adjuvant platinum/pemetrexed (preferred) or neoadjuvant chemotherapy followed by P/D. Patients are stratified by histologic subtype, resection status (R0/1 vs. R2), and center patient volume (≤10 vs. > 10 P/Ds per year). Within 8 weeks after completion of the second modality patients are randomized 1:1 to undergo hemithoracic IMPRINT vs. no further therapy. All IMPRINT contours and treatment plans will be centrally reviewed. A contouring atlas and treatment planning constraints for target structures and organs at risk including acceptable and unacceptable variations and deviations were developed. Photon and proton therapy are permitted. The primary endpoint of the study is overall survival. Secondary endpoints include local failure-free, distant-metastases-free and progression-free survival, treatment-related toxicities (CTCAE v5.0) and change in quality-of-life (EORTC QLQ-C30 mean score changes at 9 months post randomization). The target accrual is 150 patients. This study was activated on January 29, 2020. Over 20 institutions have already committed to opening the study which is open to all National Clinical Trials Network (NCTN) sites. Treatment planning guidelines and helpful hints for photon and proton therapy will be presented. Conclusions: NRG LU-006 (clinicaltrials.gov: NCT04158141 ) is open to accrual. This is the first NRG Oncology randomized phase III trial on MPM and evaluates the use of IMPRINT following lung-sparing P/D and chemotherapy. This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U24CA180803 (IROC) from the National Cancer Institute (NCI). Clinical trial information: NCT04158141.
NRG Oncology/Alliance LU005: A phase II/III randomized clinical trial of chemoradiation versus chemoradiation plus atezolizumab in limited stage small cell lung cancer.
Authors: Ross Helen J. , Hu Chen , Higgins Kristin Ann , Jabbour Salma K. , Kozono David E. , Owonikoko Taofeek Kunle , Movsas Benjamin , Solberg Timothy , Xiao Canhua , Williams Terence Marques , Welsh James William , Simko Jeffry , Wang Xiaofei F. , Mohindra Nisha Anjali , Hsu Charles , Stinchcombe Tom , Bradley Jeffrey 
Published: May 2020

TPS9082 Background: Limited stage small cell lung cancer (LS-SCLC) is treated with standard of care platinum/etoposide (EP) and thoracic radiation therapy (TRT) with curative intent, however the majority of patients are not cured and median overall survival is approximately 30 months. Addition of atezolizumab to chemotherapy in extensive stage SCLC has improved progression free and overall survival in a non-curative setting leading to hope that addition of an immune checkpoint inhibitor to standard chemoradiotherapy could benefit LS-SCLC patients. LU005 is a randomized phase II/III trial of standard concurrent chemoradiation with or without atezolizumab for patients with LS-SCLC. Methods: Patients are randomly assigned in a 1:1 ratio to standard EP chemotherapy with concurrent TRT (45 Gy BID or 66 Gy QD) with or without atezolizumab beginning concurrently with TRT, and continued every 3 weeks for up to 12 months. Eligible patients have LS-SCLC, PS 0-2, adequate organ function, no concerning comorbidities (including no active autoimmune disease) and are eligible for TRT. Patients are randomized prior to their second cycle of EP and thoracic radiation begins with the second overall cycle of chemotherapy (first cycle of study therapy) in both treatment arms. Prophylactic cranial radiation (PCI) is recommended for patients who respond to treatment. The phase II/III primary endpoints are progression free (PFS) and overall survival (OS) respectively. Secondary endpoints include objective response rates, local and distant disease control, and quality of life/patient reported outcomes assessment. Translational science component includes blood and tissue based immune related assays. This study activated in May 2019. 50 of 506 planned patients have been accrued as of 2/1/2020. Supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U23CA180803 (IROC) from the National Cancer Institute (NCI) and Genentech. *Authors Ross and Higgins are co-first authors and contributed equally to this work. Clinical trial information: NCT03811002.
Phase II randomized trial of carboplatin + pemetrexed + bevacizumab, +/- atezolizumab in stage IV non-squamous non-small lung cancer (NSCLC) patients who harbor a sensitizing EGFR mutation or have never smoked.
Authors: Bodor Joseph Nicholas , Patel Jyoti D. , Ross Eric A. , Litwin Samuel , Clapper Margie , Levy Benjamin Philip , Wakelee Heather A. , Borghaei Hossein , Treat Joseph 
Published: May 2020

TPS9629 Background: Stage IV NSCLC patients who are never-smokers or with EGFR-mutated tumors generally do not benefit from single-agent immunotherapy. Retrospective subgroup analyses from recent phase III trials suggest that immunotherapy-chemotherapy +/- VEGF inhibition may overcome resistance to PD-L1 inhibitors in these patients, however prospective research on this is needed. This trial will examine a patient population with stage IV non-squamous disease who either have tumors that possess an EGFR exon 19 or 21 mutation or who are never-smoker wild-types, to determine whether the PD-L1 inhibitor atezolizumab in combination with pemetrexed, carboplatin, and bevacizumab can improve outcomes. Methods: This is a randomized, phase II, multi-center, open-label trial to assess pemetrexed/carboplatin and bevacizumab +/- atezolizumab in 117 subjects with stage IV non-squamous NSCLC. Randomization will be 2:1 favoring the + atezolizumab arm. Patients are stratified by EGFR mutation status (i.e. EGFR exon 19 or 21 vs. never-smoker wild-type). Never-smoker wild-type is defined as smoking < 100 cigarettes in a lifetime and without any EGFR mutation or ALK or ROS1 rearrangement. Patients with EGFR exon 19 or 21 mutated tumors must have progression of disease or intolerance of treatment with one or more prior TKIs. Primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), overall response rate, duration of response, and time to response. Primary objective is to compare PFS between arms. Secondary objectives include a safety analysis in all treated subjects, and comparisons of PFS and OS between arms for the patient subset with EGFR-mutated tumors. Correlative studies include interrogating flow cytometry-based peripheral blood biomarkers, examining the role of desmoplasia in local tumor immunosuppression, and assessing the contribution of estrogen metabolites to tumorigenesis. This study opened in August 2019 with 2 patients enrolled at the time of submission. Twenty U.S. sites through the NCCN are participating. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Genentech, Inc. Clinical trial information: NCT03786692 .
A phase III, open-label, randomized study of atezolizumab in combination with carboplatin + paclitaxel + bevacizumab compared with pemetrexed + cisplatin or carboplatin with stage IV non-squamous non-small cell lung cancer (NSCLC) with activating EGFR mutation or ALK translocation (ATLAS Trial).
Authors: Park Sehhoon , Lee Yun-Gyoo , Park Ji Hyun , Lee Gyeong-Won , Kang Eun Joo , Choi Yoon Ji , Shin SeongHoon , Han Ji-Youn , Lee Suee , Kim YuJung , Kim Tae Min , Kim Sang-We , Shim Byoung Yong , Cho Jinhyun , Kim Hye Sook , Park Sang Gon , Lee Ki Hyeong , Kim Ilhwan , Ahn Myung-Ju 
Published: May 2020

TPS9636 Background: In patients with activating EGFR mutations and ALK fusion, target specific tyrosine kinase inhibitor (TKI) showed significant survival improvement compared to the cytotoxic chemotherapy. However, the questions remain which combination strategy will be the best option for the patients who have failed from TKI. Especially, the role of an immune checkpoint inhibitor (ICI) in this population is still unclear. This study is designed and conducted based on the recent subgroup analyses from the IMpower 150 study which showed the positive clinical outcomes of atezolizumab combined with VEGF inhibitor and conventional cytotoxic chemotherapy in EGFR mutation and ALK translocation. Methods: This study is the phase III, open-label, multicenter study of atezolizumab in combination with bevacizumab + carboplatin + paclitaxel (ABCP, Arm A) compared with pemetrexed + cisplatin or carboplatin (Arm B). The study population will be randomized to either Arm A (n = 152) or Arm B (n = 72) based on two stratification factors, EGFR vs. ALK and presence of brain metastases. In Arm A, patients will be treated with 4 or 6 cycles of ABCP followed by maintenance atezolizumab and bevacizumab every three weeks. In Arm B, pemetrexed maintenance therapy will be applied every three weeks after 4 or 6 cycles of pemetrexed + cisplatin or carboplatin. As key inclusion criteria, the patients must be diagnosed with stage IV non-squamous non-small cell lung cancer with either activating EGFR mutation or ALK translocation. All the patients need to be cytotoxic chemotherapy naïve and must have experienced disease progression to treatment with at least one EGFR or ALK TKI. If the patients have T790M mutation after 1st or 2nd generation EGFR TKI, second line 3rd generation EGFR TKI treatment is mandatory. The number of T790M positive patients is restricted to under 30% of the entire study population. The primary endpoint is progression-free survival and the major secondary endpoints are overall survival, objective response rate and duration of response. A total of 228 subjects will be enrolled to detect a hazard ratio of 0.67. The first subject received treatment in Aug. 2019 and 19 patients receive the treatment. This study is opened in 3 sites and expected to be opened at 18 sites in South Korea. The time point for the primary analyses is Q3. 2022. Clinical trial information: NCT03991403 .
In Vitro Control of Genes Critical for Parathyroid Embryogenesis by Extracellular Calcium
Authors: Fabbri Sergio , Zonefrati Roberto , Galli Gianna , Gronchi Giorgio , Perigli Giuliano , Borrelli Andrea , Brandi Maria Luisa 
Published: May 2020

Abstract

Background
The expression of the parathyroid transcription factors, encoded by the genes GATA3, GCM2, and MAFB, persists after parathyroid morphogenesis. This suggests a role of these genes in the regulatory program that governs parathyroid function in the adult. Indeed, these 3 genes form a transcriptional cascade able to activate PTH gene expression.

Materials and Methods
Adult adenoma parathyroid tissues were put in primary cell culture to evaluate the messenger ribonucleic acid (mRNA) expression of the PTH gene, of the genes involved in the calcium regulatory signaling pathway (CaSR, GNA11, and AP2S1), and of the 3 genes (GATA3, GCM2, and MAFB) involved in the parathyroid morphogenesis in the presence of different extracellular calcium concentrations from 0.1 mM to 3.0 mM.

Aim
The aim of the study was to investigate whether different extracellular calcium conditions could control the expression of transcription factors critical for parathyroid embryogenesis.

Results
The results of the experiments showed that the mRNA expression of GATA3, GCM2, and MAFB genes follows the same response as the PTH gene to extracellular calcium concentrations, with the highest expression at low calcium (0.1 mM) and the lowest at high calcium (3.0 mM). Conversely, the genes involved in the calcium signaling in the parathyroid cells showed a variable response to the extracellular calcium concentrations, with the CaSR and GNA11 genes exhibiting a sensitivity to low calcium concentrations.

Conclusions
These findings indicate that transcription factors recognized for their role in parathyroid embryogenesis show a response to extracellular calcium later in adulthood that parallels the behavior of the PTH gene.
Does meloxicam provide adequate pain management as a post-operative analgesic in canine ovariohysterectomy patients?
Authors: Goldsbrough Gavin , Reynolds Helen 
Published: May 2020

Background: Meloxicam is an analgesic agent with anti-inflammatory properties, commonly used in veterinary practices to treat a variety of different long-term medical conditions and is also used as a short-term pain relief following particularly traumatic surgeries. Aims: An observational study was conducted to determine whether meloxicam provides adequate pain management as a post-operative analgesic for canine ovariohysterectomies. Methods: 13 canines were admitted for ovariohysterectomy. Each patient was assessed using the Glasgow composite pain scale (CMPS) prior to surgery during the admission procedure, 15 minutes post-operatively, at discharge and at their post-operative check (POC) 3–5 days after surgery. Results: Data were statistically analysed to determine the overall effectiveness of meloxicam in reducing pain following canine ovariohysterectomy. The results showed a statistically significant difference (Kruskal-Wallis test: H3 =12.98, p=0.005) in pain scores between admission, 15 minutes post operatively, discharge and 3–5 days POC. The greatest decrease in pain score was between 15 minutes post-operatively and POC (Mann-Whitney U test: W=236, n=13, 13, p=0.0014) and between discharge and POC (Mann-Whitney U test: W=227, n=13, 13, p=0.0060). Overall, this demonstrated that there was an improvement in pain suggesting meloxicam is effective between these time frames. In addition, 69.2% (n=9) of patients in the study showed a pain score of 0, indicating an absence of pain, on their final POC. Statistical analysis was also used to determine if there was any difference in pain score between the 3, 4 or 5 day POC pain score. The results show there was no significant difference (Kruskal-Wallis test: H2 =0.090, p=0.638) suggesting that meloxicam's effectiveness was similar across this range of time post surgery. Conclusion: The results from the study indicate that meloxicam is an effective post-operative analgesic for canine patients undergoing an ovariohysterectomy.