bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postoperative follow-up of lung cancer: Randomized trial comparing two follow-up programs in completely resected non-small cell lung cancer (IFCT-0302).
Authors: Westeel Virginie , Barlesi Fabrice , Domas Jean , Girard Philippe , Foucher Pascal , Lafitte Jean-Jacques , Dumont Patrick , Wislez Marie , Quoix Elisabeth A. , Braun Denis , Lebitasy Marie Paule , Hermann Jacques , Derollez Marc , Ozenne Gervais , Raffy Olivier , Devin Etienne , Barbieux Hubert , Tredaniel Jean , Morin Franck , Debieuvre Didier ,   Intergroupe Francophone de Cancérologie Thoracique (IFCT)
Published: March 2020

TPS7111 Background: There are no robust data published on the follow-up after surgery for non-small cell lung cancer (NSCLC). Current international guidelines are informed by expert opinion. Most of them recommend regular follow-up with clinic visit and thoracic imaging, either chest X-ray of Chest CT-scan. The IFCT-0302 trial addresses the question whether a surveillance program with chest CT-scan and fiberoptic bronchoscopy can improve survival compared to a follow-up only based on physical examination and chest x-ray. There is no such trial ongoing over the world. Methods: The IFCT-0302 trial is a multicenter open-label controlled randomized phase III trial. The objective of the trial is to compare two follow-up programs after surgery for stage I-IIIa NSCLC. The primary endpoint is overall survival. Patients are randomly assigned to arm 1, minimal follow-up, including physical examination and chest x-ray; or arm 2, a follow-up consisting of physical examination and chest x-ray plus chest CT scan and fiberoptic bronchoscopy (optional for adenocarcinomas). In both arms, follow-up procedures are performed every 6 months during the first two postoperative years, and every year between the third and the fifth years. The main eligibility criteria include: completely resected stage I-IIIA (6th UICC TNM classification) or T4 (in case of nodules in the same lobe as the tumor) N0 M0 NSCLC, surgery within the previous 8 weeks. Patients who have received and/or who will receive pre/post-operative chemotherapy and/or radiotherapy are eligible. Statistical considerations: 1,744 patients is required. Accrual status: 1,568 patients from 119 French centers had been included. The end of accrual can be expected for September 2012. Ancillary study: Blood samples are collected in 1000 patients for genomic high density SNP micro-array analysis. This collection will contribute to the French genome wide association study (gwas) of lung cancer gene susceptibility, and the genetic factors predictive of survival and lung cancer recurrence will be analyzed.
AvaALL: Open-label randomized phase IIIb trial evaluating the efficacy and safety of standard of care with or without continuous bevacizumab (BV) treatment beyond disease progression in patients (pts) with advanced nonsquamous non-small cell lung cancer (NSCLC) after first-line (1L) treatment with BV plus platinum-doublet chemotherapy (CT).
Authors: Gridelli Cesare , Bennouna Jaafar , De Castro Javier , Dingemans Anne-Marie C. , Griesinger Frank , Grossi Francesco , Thatcher Nick , Ohe Yuichiro , Perez-Moreno Pablo Diego , Langer Corey J. 
Published: March 2020

TPS7612 Background: Pts with NSCLC have a poor prognosis upon progression following 1L CT. Although the disease may have progressed on 1L CT, it is likely still dependent on VEGF-mediated pathways. Thus, persistent VEGF suppression along with second- and third-line cytotoxic regimens may yield clinical benefit. Analyses have associated this strategy with improved survival in NSCLC (Nadler et al, Oncologist 2011) and mCRC (Grothey et al JCO 2008). Methods: AvaALL (MO22097; NCT01351415), a multicenter (144 centers, 20 countries) open-label randomized (1:1) 2-arm phase IIIb study, recruits pts with advanced non-squamous NSCLC that has progressed after 1L treatment with BV plus a platinum-doublet and at least 2 cycles of BV maintenance monotherapy. Pts in the experimental arm receive BV at the same dose from induction (7.5 or 15 mg/kg IV on D1 of every 21-day cycle) continuously along subsequent lines, plus investigator’s choice of second-line agent (limited to pemetrexed, docetaxel, or erlotinib) and subsequent lines of treatment. Pts in the control arm receive investigator’s choice of agent alone in second and subsequent lines of treatment, but no further BV treatment. Stratifications include nature of second-line standard treatment, number of cycles of BV maintenance (≤6 vs. >6) and smoking status. The primary endpoint is overall survival (OS). Secondary endpoints include 6-, 12-, and 18-month OS rates, progression-free survival, time to progression at second and third progressive disease (PD), response rate, disease control rate, duration of response at second and third PD, and safety of BV across multiple lines of treatment. Exploratory objectives include quality of life assessment through multiple treatment lines, and biomarker analysis. Assuming a median OS beyond PD of 7.9 months in the control group and 10.1 months in the treatment arm (HR 0.78), 528 events are required to achieve 80% power for the log-rank test at a 2-sided significance level of 5%. Enrollment began in June 2011.
The MetLUNG study: A randomized, double-blind, phase III study of onartuzumab (MetMAb) plus erlotinib versus placebo plus erlotinib in patients with advanced, MET-positive non-small cell lung cancer (NSCLC).
Authors: Spigel David R. , Edelman Martin J. , Mok Tony , O'Byrne Kenneth John , Paz-Ares Luis , Yu Wei , Rittweger Karen , Thurm Holger C. ,   on behalf of the MetLUNG Phase III Study Group
Published: March 2020

TPS7616 Background: Increased Met signaling is associated with poor prognosis in NSCLC and can result in acquired resistance to epidermal growth factor receptor (EGFR)-targeted drugs in EGFR-mutant lung tumors. Onartuzumab (MetMAb) is a humanized monovalent monoclonal antibody that binds to Met with high specificity, preventing HGF ligand binding and blocking downstream signaling. Onartuzumab has shown anticancer activity in preclinical studies (Merchant et al. AACR 2008:Abstr. 1336) and in a phase I study of patients with advanced solid tumors (Moss et al. Ann Oncol 2010;21(Suppl. 8):Abstr. 504P). In a phase II study, patients with Met-positive tumors (≥50% of tumor cells stain 2+ or 3+ intensity by IHC) (Met Dx+) who received onartuzumab + erlotinib had nearly twofold reduction in the risk of disease progression and threefold reduction in the risk of death compared with erlotinib alone (Spigel et al. J Clin Oncol 2011;29(Suppl.):Abstr. 7505). An increased incidence of peripheral edema was observed in patients treated with onartuzumab. Methods: This is a randomized, phase III, multicenter, double-blind, placebo-controlled study. Adults with Met Dx+ tumors who failed at least 1 but no more than 2 prior lines of platinum-based chemotherapy for advanced NSCLC are eligible. Around 480 patients will receive (1:1) erlotinib (150 mg PO daily) + placebo or onartuzumab (15 mg/kg IV Q3W) until disease progression, unacceptable toxicity, patient/physician decision to discontinue, or death. Patients are stratified for Met expression (2+ vs 3+), prior lines of therapy (1 vs 2), histology (squamous vs nonsquamous) and EGFR-activating mutation status (yes vs no). The primary endpoint is OS. Secondary endpoints include PFS, response rates, safety, patient-reported outcomes, and PK. An IDMC will monitor safety every 6 months after the 1st patient is enrolled and evaluate 1 interim analysis when ~67% of the total OS events have occurred. This study is open for accrual; further details can be found on ClinicalTrials.gov (NCT01456325).
Pilot study of MAGE-A3 protein vaccination and autologous stem cell transplantation (autoSCT) as consolidation therapy for multiple myeloma (MM).
Authors: Cohen Adam D. , Lendvai Nikoletta , Gnjatic Sacha , Jungbluth Achim A , Pan Linda S. , Bertolini Stephane V. , Venhaus Ralph Rudolph , Fellague-Chebra Rafik , Gruselle Olivier , Cho Hearn J. 
Published: March 2020

TPS8111 Background: MAGE-A3 is a cancer-testis antigen (CT Ag) commonly expressed in MM but not in normal non-gonadal tissues. MAGE-A3 inhibited p53-dependent and independent apoptosis in MM cells (Clin Cancer Res 2011;17:4309), and spontaneous immunity against CT Ags in MM patients was associated with favorable clinical outcomes (Blood 2007;109:1103; Blood 2008;112:3362), making it a rational target for immunotherapy. In this study (NCT01380145), we are examining if a recombinant (rec) MAGE-A3 protein vaccine + adjuvant combined with vaccine-primed peripheral blood lymphocytes (PBL) can safely stimulate antigen-specific immunity in MM patients undergoing autoSCT for consolidation therapy. Methods: Patients meeting the following criteria are eligible: within 12 months of diagnosis; MAGE-A+ MM cells by immunohistochemistry; achieving at least a very good partial response with induction therapy; and meeting institutional criteria for autoSCT. One patient of a planned cohort of sixteen has been enrolled. Six weeks before SCT, subjects will receive their first vaccination (300 μg IM) and three weeks later undergo leukopheresis to collect vaccine-primed PBL. They then undergo stem cell mobilization followed by a standard melphalan-conditioned autoSCT. On day 3 after stem cell infusion, the unmanipulated, primed PBL will be re-infused followed by the second recMAGE-A3 vaccination on day 10. An additional six vaccinations will be administered on days 31, 52, 73, 94, 180, and 270 after autoSCT. The primary objectives are safety and tolerability. The secondary objectives of cellular and humoral immune responses and lymphocyte reconstitution will be assessed by a validated series of quantitative assays using established response criteria (PNAS 2008;105:1650). Success criteria based on immune response have not been specified for this pilot study, though induction of MAGE-A3 immunity in at least 50% of patients would merit consideration for further evaluation of clinical efficacy.
Phase I/II open-label, multiple-dose, dose-escalation study to evaluate the safety and tolerability of SNS01T administered by intravenous infusion in patients with relapsed or refractory multiple myeloma.
Authors: Lust John Anthony , Barranco Charles , Lacy Martha , Dispenzieri Angela , Gertz Morie A. , Dingli David , Russell Stephen J. , Buadi Francis , Zeldenrust Steven R. , Hayman Suzanne R. , Rajkumar S. Vincent , Kumar Shaji , Usmani Saad Zafar , Thompson John , Taylor Catherine , Dondero Richard 
Published: March 2020

TPS8116 Background: Eukaryotic translation initiation Factor 5A (eIF5A) has been implicated in the regulation of apoptosis and is the only known protein to be modified by hypusination. Hypusinated eIF5A is the predominant form of eIF5A in cancer cells. However, in its unhypusinated form, eIF5A is pro-apoptotic. SNS01-T, designed to treat myeloma, consists of two components: a plasmid DNA expressing eIF5AK50R (human eIF5A containing a lysine to arginine substitution at position 50) which remains pro-apoptotic because it cannot be hypusinated, and an siRNA against an untranslated region of native eIF5A mRNA. When these two components are combined with linear polyethyleneimine (PEI), the nucleic acids are condensed into nanoparticles for protection from degradation in the blood and enhanced delivery to tissues. The eIF5AK50R transgene is under the control of the B29 promoter and enhancer, which restricts expression to B cells. The mode of action of SNS01-T is to use an eIF5A-specific siRNA to deplete the pool of hypusinated eIF5A in myeloma cells while simultaneously adding pro-apoptotic eIF5AK50R. In vitro cell studies and in vivo xenograft studies have demonstrated the efficacy of this approach. Methods: Eligible patients are enrolled sequentially into four cohorts of increasingly higher doses. Each cohort will receive SNS01-T by intravenous infusion twice weekly for 6 consecutive weeks and then be observed every 4 weeks during a 24-week follow-up period. Eligible patients must have been diagnosed with multiple myeloma according to IMWG criteria, have measurable disease, have relapsed disease after two or more prior treatment regimens, have a life expectancy of at least 3 months, and not be eligible to receive any other standard therapy known to extend life expectancy. The primary objective is to evaluate the safety and tolerability of multiple escalating doses of SNS01-T. Secondary objectives include pharmacokinetics, immunogenicity studies, proinflammatory cytokine quantitation, and therapeutic efficacy. Two of the planned 15 patients have been enrolled. (Clinical Trials.gov Identifier: NCT01435720.)
Prospective and working memory decline as a result of impaired sleep and/or impared blood glucose in breast cancer patients during chemotherapy treatment.
Authors: Moyers-Ruiz Liliana , Hickish Tamas , Thompson Simon 
Published: March 2020

TPS9148 Background: Breast cancer patients might develop impaired sleep patterns during chemotherapy, and impaired cognitive function has been associated with sleep patterns disruption. It has been suggested that sleepiness (sleep tendency) in cancer patients is prevalent and causes distress in the patient’s quality of life, that and their cognitive abilities are also affected. Furthermore, increased blood glucose levels among women undergoing chemotherapy may contrubute to memory deficits in breast cancer patients. It is proposed that Prospective and Working Memory are being affected by the disturbance of these biological factors over the course of chemotherapy. Methods: Ninety participants will be invited to take part in the study. Thirty will be breast cancer patients receiving chemotherapy treatment, thirty breast cancer patients receiving treatment other than chemotheray, and thirty healthy controls. Measures of sleep and sleepiness, will be administered at 4 testing sessions during a 9-month period, along with a neuropsychological battery. Additionally, blood samples will be analysed. Eight of planned 60 cancer patients have been enrolled, and four of them have completed the second testing session. For the assessment of sleep/wake activity, participants will be required to wear a sleeping monitor (sensewear armband) for 7 days. Pupil dilatation to observe sleepiness will be meassured by using a Pupillometry developed at Poole hospital in the UK. Prospective Memory will be assessed using CAMPROMT test to analyse if this is a more sensitive measure for mild cognitive impairment. Discussion: Impairment on variables such as sleep, sleepiness and glucose have not been studied within the context of Chemo-Brain on breast cancer patients.Therefore we want to observe whether impaired sleep and sleepiness, and impaired glucose levels are at the core of Prospective and Working Memory decline in Chemo-Brain patients in order to find a cause-and-effect relationship as a consequence of chemotherapy.
The BERNIE study: A phase II study evaluating addition of bevacizumab (Bv) to chemotherapy in children and adolescents with metastatic rhabdomyosarcoma (mRMS) and non-rhabdomyosarcoma soft tissue sarcoma (mNRSTS).
Authors: Chisholm Julia C. , Casanova Michela , Merks Johannes H. , Geoerger Birgit , Rousseau Raphael F. , Moore Nicola , Dhalluin Christophe , Oberlin Odile ,   on behalf of the European Innovative Therapies for Children with Cancer (ITCC) Consortium and the European Paediatric Soft Tissue Sarcoma Group (EpSSG)
Published: March 2020

TPS9597^ Background: Despite therapeutic advances, patient outcomes in mRMS and mNRSTS remain poor. The phase I study (Glade-Bender et al., J Clin Oncol. 2008) indicated that Bv is well tolerated in children with refractory solid tumors and yielded pharmacokinetic (PK) data that support further studies of Bv in childhood cancer. Reports of Bv used in children with solid tumors showed safety profiles consistent with data from adults. Methods: In this phase II trial, 150 patients aged 6 months to 18 years who present with mRMS or mNRSTS are randomized to receive 18 months of standard combined modality therapy as per EpSSG guidelines, either alone or with Bv. Treatment consists of 2 phases: induction therapy [9 three-weekly cycles including 4 cycles of IVADo (ifosfamide, vincristine, actinomycin D, and doxorubicin), followed by 5 cycles of IVA (i.e., without doxorubicin)] and maintenance therapy (12 four-weekly cycles of vinorelbine and cyclophosphamide). Local therapy is considered after the 6th induction cycle. Primary endpoint is event-free survival (EFS). PK sampling is performed on all patients randomized to the experimental arm during the first 4 cycles of induction. After the primary efficacy and safety analysis, all patients who have not met the primary endpoint are followed for at least 47 months for survival and long-term effects of treatment. The study enrolled 75 patients between July 2008 and January 2012; 37 patients discontinued study treatment (including 17 patients who died, all due to disease progression) and 9 patients have completed study treatment.
Effect of dexamethasone (DEX) dose modification on osteonecrosis (ON) risk associated with intensified therapies for standard risk acute lymphoblastic leukemia (SR-ALL): A report from the Children’s Oncology Group (COG) study AALL0331.
Authors: Mattano Leonard A. , Devidas Meenakshi , Friedmann Alison M. , Raetz Elizabeth A. , Hunger Stephen , Winick Naomi Joan , Carroll William L. , Maloney Kelly W. ,   Children's Oncology Group
Published: March 2020

10002 Background: ON is a known toxicity of childhood ALL therapy, particularly in patients (pts) >9 years (y). Intensified use of DEX, methotrexate (MTX), and asparaginase (ASNase) may increase the risk of developing ON among B-precursor NCI SR-ALL pts despite their younger age. Methods: Newly diagnosed SR-ALL pts 1-9y enrolled on AALL0331 between 4/05 and 5/10 were prospectively monitored for symptomatic ON within three treatment cohorts risk-stratified by clinical, cytogenetic, and early response criteria. ON sites were confirmed by imaging. SR-Low (SRL) pts were randomized to standard therapy +/- 4 additional doses of PEG-ASNase. SR-Average (SRA) pts were randomized (2x2) to standard therapy +/- an intensive consolidation (IC) +/- an augmented interim maintenance/delayed intensification (AIM/ADI). SR-High (SRH) pts all received IC and two AIM/ADI phases. After 6/08, alternate week DEX (AWD, days 1-7/15-21) replaced continuous DEX (days 1-21) during DI, and escalating-dose MTX replaced oral MTX during IM. All pts received DEX days 1-28 during induction and 5-day pulses every 4 weeks during maintenance. Results: Overall ON cumulative incidence (CI) at 5y was 2.7% (133/5261), correlating with sex (F 3.7%, M 1.9%, p<0.0001), age (1-2y 0.8%, 3-4y 2.0%, 5-6y 3.3%, 7-9y 7.8%, p<0.0001), and risk group (SRL 2.6%, SRA 2.9%, SRH 5.7%, p=0.0009). Before 6/08, ON CI was higher for SRA pts given intensive vs standard consolidation (5.8% vs 1.9%, p=0.002), and trended higher for SRL pts given additional PEG-ASNase (4.0 vs 2.3%, p=0.09). Use of AWD significantly reduced ON CI at 3y among SRH pts (7.4% vs 1.5%, p=0.003) and further reduced ON events in SRL/SRA pts. Conclusions: Young children receiving intensified therapy for SR-ALL therapy are at risk for ON. Extended exposure to PEG-ASNase is a likely contributing factor, possibly by potentiating DEX exposure during DI. ON risk can be significantly reduced by using AWD during DI, which is now COG standard of care. Clinical trial information: NCT00103285.
Bortezomib reinduction therapy to improve response rates in pediatric ALL in first relapse: A Children’s Oncology Group (COG) study (AALL07P1).
Authors: Horton Terzah M. , Lu Xiaomin , O'Brien Maureen Megan , Borowitz Michael J. , Devidas Meenakshi , Raetz Elizabeth A. , Brown Patrick Andrew , Zeng Hui , Zheng Hao W. , Hunger Stephen , Whitlock James ,   Children's Oncology Group
Published: March 2020

10003 Background: Bortezomib (bortez) is a reversible inhibitor of the 26S proteasome. Promising results have been reported adding bortezomib to reinduction chemotherapy in patients (pts) with ALL in 2nd or later relapse (Messinger, Blood 2012). Methods: This was a phase 2 study of bortez with reinduction chemotherapy in 1st relapse pediatric ALL that enrolled pts with pre-B ALL (relapse <36 months (m) from diagnosis). This report summarizes results from 61 evaluable pre-B ALL pts ≤21 yrs old, either <18m (stratum 1) or 18-36m (stratum 2) from diagnosis. Therapy consisted of bortez (1.3 mg/m2, days 1, 4, 8, and 11) with reinduction chemotherapy (vincristine, prednisone, PEG-asparaginase, doxorubicin). Complete response (CR2) rates and minimal residual disease (MRD) were determined at the end of the first 5-week therapy block. AALL07P1 utilized a stratified 2-stage design (London 2005) with the primary objective of comparing CR2 rates at the end of block 1 of therapy to historical control CR2 rates (AALL01P2). Block 2 included cyclophosphamide, etoposide, and bortez followed by 5g/m2 methotrexate. Biology studies included assessment of NF-κB activity. Results: 61 evaluable pre-B ALL pts were assessed. Toxicities were similar to AALL01P2, including 10 Grade 3- 4 hypotension, 4 Grade 4 hypertriglyceridemia, 3 Grade 3-4 typhlitis, and 2 Grade 3-4 enterocolitis. There were 2 deaths due to infection. Although Grade 3-4 infections were not infrequent (13 in block 1 and 7 in block 2) there were no reports of respiratory distress syndrome or Grade 4 peripheral neuropathy. 42 of the 61 patients enrolled (18/28 (64%) in Stratum 1 and 24/33 (73%) in stratum 2) attained CR2 at the end of Induction I. Based on CR2 response rate compared to historical controls, the study met its primary response objective. The number of pts in CR2 with MRD <0.1% also improved from AALL01P2; among pts achieving CR2, MRD was <0.1% in 41% (16/39) in AALL01P2 vs. 71% (25/35) (p= 0.073, Fisher’s exact test). Conclusions: Based on response rates in the very early and early first relapse pre-B ALL, AALL07P1 met its predefined efficacy benchmark. We conclude that bortezomib is worthy of further study in pediatric ALL. Clinical trial information: NCT00873093.