bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: Final analysis of the EORTC AMAROS trial (10981/22023).
Authors: Rutgers Emiel J. , Donker Mila , Straver Marieke Evelien , Meijnen Philip , Van De Velde Cornelis J. H. , Mansel Robert E. , Westenberg Helen , Orzalesi Lorenzo , Bouma Willem H. , van der Mijle Huub , Nieuwenhuijzen Grard A. P. , Veltkamp Sanne C. , Slaets Leen , Messina Carlo G. M. , Duez Nicole J. , Hurkmans Coen , Bogaerts Jan , van Tienhoven Geertjan 
Published: March 2020

LBA1001 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Bevacizumab, irinotecan, and radiotherapy versus standard temozolomide and radiotherapy in newly diagnosed, MGMT-non-methylated glioblastoma patients: First results from the randomized multicenter GLARIUS trial.
Authors: Herrlinger Ulrich , Schaefer Niklas , Steinbach Joachim Peter , Weyerbrock Astrid , Hau Peter , Goldbrunner Roland , Friedrich Franziska , Stockhammer Florian , Ringel Florian , Braun Christian , Kohnen Ralf , Leutgeb Barbara , Belka Claus , Urbach Horst , Stummer Walter , Glas Martin 
Published: March 2020

LBA2000 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Saturday, June, 1, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Randomized, double-blind, phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, Fallopian tube, or primary peritoneal cancer (AOC): Results of an international intergroup trial (AGO-OVAR16).
Authors: Du Bois Andreas , Floquet Anne , Kim Jae Weon , Rau Jörn , Del Campo Jose Maria , Friedlander Michael , Pignata Sandro , Fujiwara Keiichi , Vergote Ignace , Colombo Nicoletta , Mirza Mansoor Raza , Monk Bradley J. , Wimberger Pauline , Ray-Coquard Isabelle , Zang Rongyu , Diaz-Padilla Ivan , Baumann Klaus H. , Kim Jae Hoon , Harter Philipp ,   on behalf of an Intergroup consortium
Published: March 2020

LBA5503 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Saturday, June 1, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Pilot study of redirected autologous T cells engineered to contain anti-CD19 attached to TCRζ and 4-1BB signaling domains in patients with chemotherapy-resistant or -refractory CD19+ leukemia and lymphoma.
Authors: Grupp Stephan A. , Porter David L. , Levine Bruce , Kalos Michael , Strait Christine , Rheingold Susan R. , Aplenc Richard , June Carl H. 
Published: March 2020

TPS10072 Background: Outcomes remain poor for patients (pts) with relapsed or refractory (r/r) B-cell malignancies such as acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL). CD19 is an attractive therapeutic target because it is widely expressed on normal and malignant B cells throughout B-cell maturation but not on pluripotent stem cells or non–B-cell tissues. We have developed chimeric antigen receptor T cells to target CD19+ cells (CART-19 or CTL019). This approach involves patient-derived T cells that are genetically modified via lentiviral transduction to express a CD19 antigen recognition domain attached to intracellular signaling domains (TCRζ and 4-1BB) that mediate T-cell activation. A recent study in CLL showed that CART-19 therapy had potent activity with responses in 5/8 evaluable pts (3 CR, 2 PR). Pts achieving CR (two > 24 months and one > 5 months) remain in CR with detectable CART-19 cells (Porter et al. ASH 2012). Here we describe a study of CART-19 therapy in pediatric pts with r/r leukemia and lymphoma (NCT01626495). Methods: Pts eligible for this single-arm, open-label study are aged 1 to 24 years with r/r CD19+ B-cell malignancies, without a transplant option or having relapsed after allogeneic stem cell transplantation (ASCT). Pts will undergo leukapheresis to obtain T cells, which will be stimulated, expanded, and transduced ex vivo to express the chimeric antigen receptor. Pts may receive lymphodepleting chemotherapy prior to CART-19 infusion. Study objectives: determine the safety and feasibility of administering CART-19 therapy to pediatric pts, assess duration of in vivo survival of CART-19 cells, and measure antitumor response. There are 2 cohorts in the study: Cohort 1 includes pts who have not undergone ASCT and are not currently eligible for a transplant, and cohort 2 includes pts who relapsed after ASCT. Cells are collected from the recipient, not the donor, which allows for this approach to be used in pts s/p cord blood transplant, and which we hypothesize will reduce the risk of GVHD as a result of toleration of the T cells in the recipient. To date, 7 pts have been enrolled. Clinical trial information: NCT01626495.
Alliance A091102: Phase II study of MLN8237 (alisertib) in advanced/metastatic sarcoma.
Authors: Dickson Mark Andrew , Mahoney Michelle R. , Marchello Benjamin T. , Condy Mercedes M. , Tap William D. , Schwartz Gary K. 
Published: March 2020

TPS10594 Background: Approximately 13,000 cases of soft tissue and bone are diagnosed annually in the US. Despite primary surgery many patients develop recurrent disease. Response rates to chemotherapy are low and new agents are needed. Gene array studies have shown Aurora Kinase A (AURKA) commonly overexpressed. Inhibition of AURKA by shRNA or by a specific AURKA inhibitor blocks in vitro proliferation of multiple sarcoma subtypes. MLN8237 (alisertib) is a novel and oral, ATP-competitive, selective small-molecule inhibitor of AURKA. We hypothesize that alisertib will be an effective treatment for advanced/metastatic sarcoma. Methods: This CTEP-sponsored, investigator-initiated, multi-center phase II study uses alisertib in patients with advanced/metastatic sarcoma and is conducted through the Alliance for Clinical Trials in Oncology (Alliance A091102). Patients must have adequate performance status, organ function, and measurable disease (RECIST v1.1). Patients are enrolled in one of five cohorts, depending on histology: 1) liposarcoma, 2) leiomyosarcoma, 3) undifferentiated sarcoma, 4) malignant peripheral nerve sheath tumor, or 5) other. Patients are treated with alisertib 50mg PO BID d1-d7 every 21 days until either progressive disease or unacceptable toxicity. The primary endpoint is objective overall response rate (ORR). Secondary endpoints include progression-free survival (PFS) and overall survival (OS). Translational objectives include correlation of ORR, PFS and OS with baseline and post-treatment markers of AURKA inhibition in tumor biopsies and baseline and post-treatment [F-18] FLT-PET scans. A Simon two-stage design is used for each of the 5 cohorts and one confirmed response in the first 9 patients expands enrollment in that cohort to 24. Enrollment began in December 2012. As of January 2013, 14 pts have been enrolled. Funded by the Alliance for Clinical Trials in Oncology. Clinical trial information: NCT01653028.
Phase I/II study of the safety, pharmacokinetics, and efficacy of pomalidomide in the treatment of Kaposi sarcoma in individuals with or without HIV.
Authors: Polizzotto Mark Niccolo , Uldrick Thomas S. , Wyvill Kathleen , Aleman Karen , Sereti Irini , Tosato Giovanna , Whitby Denise , Bevans Margaret , Maldarelli Frank , Figg William Douglas , Steinberg Seth M. , Yarchoan Robert 
Published: March 2020

TPS10595 Background: Kaposi sarcoma (KS) is a multicentric angioproliferative tumor seen most frequently in people with HIV. It is caused by the gammaherpesvirus Kaposi-sarcoma associated herpesvirus (KSHV, or human herpesvirus 8) and is remarkable for its tendency to progress or regress based on host immune factors. Pomalidomide is an orally available third generation thalidomide derivative with immunomodulatory and antiangiogenic properties that may address unmet clinical needs in KS. Methods: The primary objective is to assess the safety, tolerability and pharmacokinetics of pomalidomide in subjects with KS, whether HIV associated or not, and to explore its antitumor effect at the tolerable dose once determined. This is the first assessment of this agent in patients with HIV and/or KS. Subjects with confirmed KS and no symptomatic pulmonary or visceral KS are eligible. Those with HIV must be compliant with HAART; have achieved an HIV viral load <10,000 copies/mL; and in the phase II portion have KS increasing despite HAART and HIV suppression for ≥2months, or stable despite HAART for ≥3months. In the phase I portion, up to 6 subjects will be treated with pomalidomide 5mg orally daily for 21 days of a 28 day cycle. Subject to evaluation of adverse events and tolerability, this may be deescalated to 3mg orally daily 21 of 28 days in a second cohort of up to 6 subjects. If either dose proves tolerable, the study will proceed to the phase II portion, and enroll up to 15 HIV positive and 10 HIV negative subjects. Antitumor activity will be assessed using modified ACTG KS response criteria in parallel with quality of life assessment. Key correlative studies include evaluation of immune responses including T cell numbers and activation in peripheral blood and tumor tissue and KSHV specific T-cell responses; HIV and KSHV activity and associated cytokines; and the first exploration of effects of pomalidomide pharmacokinetics when administered with common antiretroviral agents. Progress: The study opened to accrual in January 2012. The phase I portion is complete with no DLTs at the dose of 5mg 21 of 28 days. Phase II has accrued 11 subjects (4 HIV negative, 7 HIV positive) at this dose. Clinical trial information: NCT01495598.
Identification and validation of an assay predictive of response and prognosis following anthracycline-based chemotherapy for early breast cancer.
Authors: Mulligan Jude M. , Hill Laura A. , Deharo Steve , Keating Katherine E. , Raji Olaide , McDyer Fionnuala A. , James Jacqueline , Irwin Gareth , Boyle David , Quinn Jennifer E. , Mullan Paul B. , James Colin R. , Salto-Tellez Manuel , Davison Timothy S. , Johnston Patrick , Couch Fergus J. , Harkin D. Paul , Kennedy Richard D. 
Published: March 2020

TPS11120 Background: Currently there is no biomarker to predict specific benefit from DNA-damaging anthracycline and cyclophosphamide-based chemotherapy in the clinic. Loss of the Fanconi anemia/BRCA (FA/BRCA) DNA-damage response pathway occurs in approximately 25% of breast cancer and results in sensitivity to DNA-damaging agents. We therefore developed an assay to detect loss of the FA/BRCA pathway, for the purpose of predicting benefit from chemotherapy. Methods: 21 FA patient samples were analyzed to identify genetic processes associated with loss of the FA/BRCA pathway. Unsupervised hierarchical clustering was then performed using 60 BRCA1/2 mutant and 47 sporadic tumor samples and a molecular subgroup was identified that was defined by the molecular processes representing loss of the FA/BRCA pathway. A 44-gene DNA Damage response deficient (DDRD) assay was developed that could identify this subgroup from formalin fixed, paraffin embedded (FFPE) samples in the clinic. Results: In a publicly available independent cohort of 204 patients, the assay predicted response to neoadjuvant DNA-damaging chemotherapy (5-fluorouracil, anthracycline and cyclophosphamide) with an odds ratio of 4.01, (95% Cl:1.69-9.54). We also analysed samples from an independent cohort of 114 node-negative breast cancer patients treated with adjuvant 5-fluorouracil, epirubicin and cyclophosphamide treatment at the Northern Ireland Cancer Centre. The DDRD assay significantly predicted 5-year relapse free survival with a hazard ratio of 0.27 (95% Cl:0.10-0.83). The assay was not predictive of survival in patients who did not receive chemotherapy. Conclusions: An FFPE tissue-based assay that detects loss of the FA/BRCA pathway has been developed and independently validated as a predictor of response and prognosis following DNA damaging anthracycline/cyclophosphamide-based chemotherapy in the neoadjuvant and adjuvant settings.
Correlation of 64Cu-DOTA-trastuzumab positron emission tomography (PET) imaging with HER2 status by immunohistochemistry (IHC).
Authors: Mortimer Joanne E. , Park Jinha Mark , Carroll Mary I. , Poku Kofi , Miles Joshua , Colcher David , Raubitschek Andrew Antony , Tran Tri , Bading James R. 
Published: March 2020

TPS11121 Background: We have developed 64Cu-DOTA-trastuzumab for PET imaging of HER2-positive breast cancer. We have determined that administering trastuzumab (45 mg) prior to 64Cu-DOTA-trastuzumab sharply reduces liver uptake of the radiotracer. We are now testing whether tumor uptake of 64Cu-DOTA-trastuzumab correlates with variable IHC staining in women with advanced breast cancer. Methods: Eligibility criteria included biopsy confirmation of metastatic disease that was HER2 1+, 2+, or 3+ by IHC, no anti-HER therapy within the prior 4 mo, and at least 1 non-hepatic site of metastasis > 20 mm outside the biopsy site. Staging workup included 18F-FDG PET-CT. Patients received 45 mg of cold trastuzumab prior to 64Cu-DOTA-trastuzumab. PET-CT scans were obtained at 21-25 h (Day 1) and 47-48 h (Day 2) over axial fields of view chosen in reference to 18F-FDG. Uptake in prominent lesions was measured in terms of maximum single-voxel SUV (SUVmax). Lesions identified on CT and judged to have image intensity > adjacent tissue by an expert radiologist were considered positive on PET. Results: Fourteen women (median age 56, range 35-75 y) have undergone imaging. HER2 status by IHC was 3+ in 9 pts., 2+ in 5 and 1+ in 1. Two women with IHC 2+ disease were FISH+. In the patients considered clinically HER2 positive (IHC 3+ or 2+, FISH+), 64Cu-DOTA-trastuzumab sensitivity was 75 and 90%, respectively, on Days 1 and 2, compared with 94% for 18F-FDG. Tumor uptake of 64Cu-DOTA-trastuzumab was also readily visualized in HER2-negative patients (measured detection sensitivity 90%). There were no false positive findings with 64Cu-DOTA-trastuzumab. Lesion uptake of 64Cu-DOTA-trastuzumab was higher in HER2+ than in HER2- patients (SUVmaxmean ± sem: Day 1 8.9±0.6 vs 4.3±0.2; Day 2 9.9±0.8 vs 5.4±0.3, p < 0.001). Conclusions:64Cu-DOTA-trastuzumab PET visualizes HER2 1+, 2+ and 3+ metastatic breast cancer with high sensitivity and specificity. Tumor uptake of 64Cu-DOTA-trastuzumab-PET in IHC 1+ and 2+ patients implies possible benefit from anti-HER2 therapies for individuals whose cancers are currently considered HER2 negative. Research Support: DOD1024511. Clinical trial information: NCT01093612.
NSABP B-47: A randomized phase III trial of adjuvant therapy comparing chemotherapy alone to chemotherapy plus trastuzumab in women with node-positive or high-risk node-negative HER2-low invasive breast cancer.
Authors: Fehrenbacher Louis , Jeong Jong-Hyeon , Rastogi Priya , Geyer Charles E. , Paik Soonmyung , Ganz Patricia A. , Land Stephanie R. , Costantino Joseph P. , Swain Sandra M. , Mamounas Eleftherios P. , Wolmark Norman 
Published: March 2020

TPS1139 Background: Adjuvant trastuzumab trials in HER2+ breast cancer (BC) demonstrated a large reduction in recurrence and death. Central testing showed HER2 non-amplified participants derived similar benefit. Among HER2-amplified patients (pts), multiple studies showed no effect on benefit by degree of amplification. Blinded internal and external review confirmed the non-amplified nature of the HER2 normal group. Based on these findings, NSABP B-47, sponsored by the NCI, was activated January 2011 and is actively accruing. The study is NCI central IRB approved, open via the CTSU, and endorsed by SWOG, ECOG, and RTOG. Methods: Study: Chemotherapy treatment is by physician choice: The non-anthracycline regimen is TC (docetaxel 75 mg/m2, cyclophosphamide (C) 600 mg/m2) IV q 3 wks for 6 cycles; the anthracycline regimen is AC → WP (doxorubicin 60 mg/m2 and C 600 mg/m2 IV either q 3 wks or q 2 wks [investigator discretion] for 4 cycles → paclitaxel 80 mg/m2 IV wkly for 12 doses). Pts are randomly assigned to chemotherapy with or without trastuzumab for 1 year. Pts receive adjuvant radiation therapy and endocrine therapy, as clinically indicated. Detailed menstrual history, concurrent medications, weight changes, and biomarkers (estrogen, stress, inflammation), are being collected. Eligibility: Eligibility includes: node positive or high risk node negative BC pts; HER2 IHC 1+ or 2+ scores, but non amplified by FISH; normal cardiac, renal, and liver function. Detailed eligibility will be provided. Statistical Design: The primary aim is to determine whether the addition of trastuzumab to chemotherapy improves invasive disease-free survival (IDFS). 3,260 pts will be enrolled to provide statistical power of 0.9 to detect a 33% reduction in the hazard rate of IDFS using a one-sided alpha level of 0.025. Progress: Protocol was activated in January 2011. First pt was entered in February 2011. As of January 23, 2013, 1,416 of 3,260 (43.4 %) pts have been enrolled. Updated information on enrollment and study background will be provided. Support: NCI U10-12027, -37377, 69651, 69974, and Genentech, Inc. Clinical trial information: NCT01275677.
A randomized phase III trial comparing nanoparticle-based paclitaxel with solvent-based paclitaxel as part of neoadjuvant chemotherapy for patients with early breast cancer (GeparSepto): GBG 69.
Authors: Jackisch Christian , Wiebringhaus Frank , Conrad Bettina , Weigel Michael , Aktas Bahriye , Wagner Harald , Latos Kunibert , Kohls Andreas , Bueckner Ute , Hauzenberger Tanja , Bangemann Nikola , Hackmann John , Clemens Michael R. , Heinrich Bernhard , Tome Oliver , Loibl Sibylle , Nekljudova Valentina , Von Minckwitz Gunter ,   German Breast Group
Published: March 2020

TPS1141 Background: Anthracyclines (A) followed by taxanes (T) are standard of care for neoadjuvant therapy in breast cancer (BC). A reverse sequence of T followed by A was suggested to achieve higher pCR rates. Previous studies have shown that dual anti-HER2 blockade is superior to trastuzumab (H) alone and thus can increase the pCR rate by 20%. Nab-paclitaxel (nP) is a solvent-free formulation of P encapsulated in albumin and might also improve the pCR rate with eventually lower toxicity. Methods: The GeparSepto study (NCT01583426) will randomize 1200 patients to either nP (150 mg/m²) q1w or P (80mg/m²) q1w for 12 weeks followed by 4 cycles conventionally dosed EC (E 90mg/m², C 600 mg/m²) q3w for 4 cycles. Primary objective is to compare the pCR rate (ypT0+ ypN0). Patients with untreated, histologically confirmed cT2- cT4d BC can be included. HER2+ patients receive H (loading dose 8mg/kg; 6 mg/kg) plus pertuzumab (loading dose 840 mg; 420 mg) q3w concomitantly. Biomaterial including FFPE from core biopsy, serum, plasma and full blood is collected. HER2, ER, PgR, Ki67 and SPARC status will be centrally assessed prior to randomization for stratification. P was assumed to achieve a pCR rate of 33% which will be increased to 41% when using nP, corresponding to an odds ratio of 1.41. To investigate resistance to anti-HER2 treatment, patients with HER2+ BC are randomized prior to start of chemotherapy to receive either 6 weeks H, pertuzumab or the combination as biological window with biomaterial collection prior to start of therapy and after week 6 prior to start of chemotherapy. Results: After been approved by ethics committees and authorities recruitment started in 7/2012 in 56 sites. 293 patients were recruited (53 HER2+; 240 HER2-) by 1st Feb 2013. A first safety interim analysis is planned after 60 patients have finished therapy. Conclusions: GeparSepto investigates the efficacy of neoadjuvant nP compared to solvent-based P given weekly with a dual blockade of the HER2 receptor in HER2-pos BC. Interim safety results for nP will be presented. The window-substudy is funded within the EU-FP7 project RESPONSIFY No 278659. Clinical trial information: NCT01583426.
Phase I/II dose-escalation study of VB-111, an antiangiogenic gene therapy, in patients with recurrent glioblastoma multiforme.
Authors: Brenner Andrew Jacob , Cohen Yael , Vredenburgh James J , Peters Katherine B. , Breitbart Eyal , Bangio Livnat , Sher Naamit , Harats Dror , Wen Patrick Y. 
Published: March 2020

TPS2102 Background: VB-111 is an anti-angiogenic agent consisting of a non-replicating adenovirus vector (Ad-5) with a modified murine pre-proendothelin promoter leading to apoptosis of tumor vasculature by expressing a fas-chimera transgene in angiogenic endothelial cells. In a phase I/II dose-escalation study, safety and efficacy of VB-111 in patients with recurrent Glioblastoma Multiforme (GBM) were evaluated. Methods: VB-111 was administered as a single intravenous infusion at escalating doses from 1x1012 to 3x1012 viral particles (VPs), followed by repeat doses of 3x1012 or 1x1013every 2 months. Assessments included safety, pharmacokinetics, tumor response (RANO criteria) and overall survival (OS). Results: Twenty eight patients aged 26 – 74 years at 3 medical centers in the US received up to 8 repeat doses of VB-111. The median OS was 360 [range: 70-574] and 266 days [range: 28-664] for patients receiving at least one dose of 1x1013VPs (high dose) vs. subjects who received lower doses, respectively (p NS). Progression free survival was 87 vs 55 days for patients who received high dose and for lower doses, respectively (p = 0.01). Median follow-up was 232 days. Three patients had a partial response (PR) at 82, 86 and 408 days post initial VB-111 dosing. Twenty one of the patients who progressed on VB-111 treatment received bevacizumab off study; 7 of the 15 evaluable patients (47%) had a PR compared to 30% expected according to literature. VB-111 was safe and well tolerated, 53 adverse events were reported, 14 were classified as possibly related to VB-111. All events were of CTCAE grade 1-2 except one grade 3 pulmonary embolism. There were no study related deaths. One patient developed peri-tumoral edema, which resolved with corticosteroid therapy. Events occurring in > 10% of the patients included headache and fatigue. Conclusions: VB-111 was safe and well tolerated in patients with recurrent GBM with repeat doses of up to 1x1013 VPs. Tumor responses were seen. Overall survival was about 3 months longer than historical data in recurrent GBM, including standard of care anti-angiogenic agents. Data suggests that VB-111 potentiates the response to bevacizumab given at further progression. Clinical trial information: NCT01260506.