bluuebunny/crossref_metadata_2025_split huggingface dataset:
DETECT III: A multicenter, randomized, phase III study to compare standard therapy alone versus standard therapy plus lapatinib in patients (pts) with initially HER2-negative metastatic breast cancer but with HER2-positive circulating tumor cells (CTC).
Authors: Hagenbeck Carsten , Melcher Carola Anna , Janni Johann Wolfgang , Schneeweiss Andreas , Fasching Peter A. , Aktas Bahriye , Pantel Klaus , Solomayer Erich-Franz , Ortmann Uta , Jaeger Bernadette Anna Sophia , Mueller Volkmar , Fehm Tanja N. 
Published: March 2020

TPS1146 Background: HER2 status may change over the course of disease in breast cancer pts. Approx. 20-30% of pts with initially HER2-negative breast cancer have HER2-positive metastasis (Zidan et al. 2005; Tewes et al. 2009). Determining HER2 status on CTC is one option to re-evaluate HER2 status at the time metastasis is diagnosed. Currently it is unclear if HER2-targeted therapy based on the assessment of HER2 status of CTC reveals a clinical benefit. Methods: This is a randomized, open-label, two arm phase III study to investigate the clinical efficacy of lapatinib, as a HER2-targeted therapy in initially HER2-negative metastatic breast cancer pts with HER2-positive CTC at the time of distant disease. As only half of the pts with HER2-negative metastatic breast cancer show CTC-positivity and of those approx. 32% will exhibit HER2-positive CTC (Fehm et al. 2010), screening of about 1420 pts is required to enroll 228 pts. Main inclusion criteria: metastatic breast cancer with HER2-negative primary tumor tissue and/or biopsies from metastatic sites or locoregional recurrences, evidence of ≥1 HER2-positive CTC and ≥1 measurable metastatic lesion according to RECIST. Eligible pts will be randomized 1:1 to receive standard treatment vs. standard treatment plus lapatinib. Standard chemo- or endocrine therapy must be approved in combination with lapatinib or been investigated in prior clinical trials. Primary endpoint is progression free survival. Secondary endpoints include overall response rate, clinical benefit rate, overall survival and dynamic of CTC. The DETECT III trial is one of the first trials where treatment is based on phenotypic characteristics of CTC. If this trial succeeds in proving efficacy of lapatinib in pts with initially HER2-negative metastatic breast cancer but HER2-positive CTC, this will establish a new strategy in the treatment of metastatic breast cancer.
Phase II study of the multikinase inhibitor dovitinib (TKI258) or placebo in combination with fulvestrant in postmenopausal, endocrine resistant HER2-/HR+ breast cancer.
Authors: Andre Fabrice , Greil Richard , Denduluri Neelima , Yovine Alejandro Javier , Reddick Cathy , Squires Matthew , Zhang Yong , Blackwell Kimberly 
Published: March 2020

TPS1148 Background: Overcoming endocrine resistance is a critical goal in the treatment of hormone receptor−positive (HR+) breast cancer. Molecular mechanisms associated with endocrine resistance include adaptive “cross-talk” between the estrogen receptor and the fibroblast growth factor receptor (FGFR). Up to 8% of HR+/HER2- breast cancer patients (pts) have amplification of the FGFR1 gene, which is associated with resistance to endocrine therapy but can be overcome via FGFR1 inhibition in preclinical models. Dovitinib is a potent FGF, VEGF, and PDGF receptor tyrosine kinase inhibitor that demonstrated antitumor activity in heavily pretreated breast cancer pts with FGF pathway amplification (FGFR1, FGFR2, or ligand FGF3; Andre et al, ASCO 2011). Dovitinib may reverse resistance to endocrine therapy related to FGF-pathway amplification and is studied here to determine if it can improve outcomes when combined with fulvestrant. Methods: Postmenopausal HER2-/HR+ locally advanced or metastatic breast cancer pts (N»150) progressing within 12 months of completion of adjuvant endocrine therapy or after ≤ 1 prior endocrine therapy in the advanced setting will be enrolled in this multicenter, randomized, double blind, placebo controlled, phase II trial. Pts will prospectively undergo molecular screening to enrich for FGF-amplification (FGFR1, FGFR2, or FGF3 amplification by qPCR; 45 amplified and 30 non-amplified pts per arm). Pts will be randomized 1:1 to receive fulvestrant (500 mg q4w [with an additional dose 2 wks after the initial dose]) in combination with oral dovitinib (500 mg, 5 days on/2 days off) or placebo until disease progression, unacceptable toxicity, or death. The primary endpoint is progression-free survival, with tumor assessments performed q8w. Secondary endpoints include overall response rate per RECIST v1.1, duration of response, overall survival, ECOG performance status and patient reported outcome scores over time, and safety. The pharmacodynamic effect of dovitinib on FGFR-associated angiogenic pathways in tumor specimens and potential predictive biomarkers of response to dovitinib will be explored.
REACT: A phase II study of rindopepimut (CDX-110) plus bevacizumab (BV) in relapsed glioblastoma (GB).
Authors: Reardon David A. , Vredenburgh James J. , Desjardins Annick , Steis Ronald G. , Dunbar Erin M. , Chandramouli Nitin B. , Rixe Olivier , Green Jennifer A , Davis Thomas A. , Sampson John Howard ,   ReACT Study Group
Published: March 2020

TPS2103 Background: EGFRvIII is a constitutively active tumorigenic deletion mutation of EGFR. It is expressed in ~30% of primary GB where it is linked to poor long-term survival (Pelloski 2007). The investigational vaccine rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally (500ug with 150ug GM-CSF as an adjuvant). Remarkably consistent and promising results across 3 phase II studies in newly diagnosed, resected EGFRvIII+ GB (Lai 2011) represent a statistically significant improvement over a historical control cohort matched for major eligibility criteria (median overall survival [OS] = 24.4 - 24.6 vs. 15.2 months from diagnosis [m] and median progression-free survival [PFS] = 12.3 - 15.3 vs. 6.4 m). ACT IV, a phase III trial in this population, is ongoing. The immunosuppressive influence of residual/advanced GB presents a challenge to activation of efficacious antitumor immune responses. Anecdotal evidence (compassionate use cases, Sampson 2008) suggests that rindopepimut may induce specific immune responses and regression in multifocal and bulky residual tumors. Rindopepimut with BV, which inhibits VEGF and its immunosuppressive properties (including impaired maturation of dendritic cells and disruption of tumoral T cell infiltration [Johnson 2007, Shrimali 2010]) may further optimize EGFRvIII-specific immune response and antitumor activity. Methods: ReACT is a Phase II study of rindopepimut plus BV in patients (pts) with 1st or 2nd relapse of EGFRvIII+ GB. BV-naïve pts will be enrolled to Group 1 (n=70: randomized 1:1 to BV plus either rindopepimut/GM-CSF or control injection [low-dose KLH]) while BV-refractory patients will enter Group 2 (n=25: to receive BV plus open-label rindopepimut/GM-CSF). Concurrent with BV (10 mg/kg, q 2 wks), blinded treatment or open-label vaccine is given in priming phase (days 1, 15 and 29), then monthly until PD. Tumor response is assessed every 8 weeks, and patients are followed for survival after PD. Objectives are PFS at 6 months (primary), objective response rate, PFS, OS, safety, immunogenicity and elimination of EGFRvIII. ReACT opened to accrual in December 2011 (NCT01498328).
A phase III randomized controlled trial of short-course radiotherapy with or without concomitant and adjuvant temozolomide in elderly patients with glioblastoma (NCIC CTG CE.6, EORTC 26062-22061, TROG 08.02, NCT00482677).
Authors: Perry James R. , O'Callaghan Christopher J , Ding Keyue , Roa Wilson , Mason Warren P. , Cairncross J. Gregory , Brandes Alba Ariela , Menten Johan , Phillips Claire , Fay Michael F. , Nishikawa Ryo , Winch Chad , Laperriere Normand 
Published: March 2020

TPS2104 Background: The EORTC (26981-22981)/NCIC CTG (CE.3) RCT in newly diagnosed GBM found improved survival with concomitant and adjuvant temozolomide (TMZ) added to radiotherapy (RT). Study pts were 18-71 (median 56) years; however a sub-group analysis noted a trend of decreasing benefit from the addition of TMZ with increasing age, such that for age 65-71, the hazard ratio of 0.8 did not reach statistical significance (p=0.340). Recent RCTs in elderly GBM found improved survival with RT compared to supportive care alone and detected non-inferiority of 40 Gy/15 vs. a 60 Gy/30 RT regimen. Based upon these results short-course hypofractionated RT is often recommended for elderly pts. However, whether the addition of TMZ to RT confers a survival advantage in elderly pts remains unanswered. Methods: Patients ≥65 yrs of age with histologically confirmed newly diagnosed glioblastoma, ECOG 0-2, are randomized 1:1 to receive 40Gy/15 RT vs. 40Gy/15 RT with 3 weeks of concomitant temozolomide plus monthly adjuvant TMZ until progression or 12 cycles. Stratification is by centre, age (65-70, 71-75, or 76+), ECOG 0,1 vs 2, and biopsy vs resection. For 90% power to detect a 25% reduction in the primary outcome of overall survival (increased MST from 6 to 8 months) between arms, using a two-sided 5% alpha, a minimum of 520 deaths must be observed prior to analysis; total sample size is 560 patients. The trial is open in Canada (NCIC CTG), Europe (EORTC), Australia and New Zealand (TROG), and Japan. As of Jan 25, 2012, 361 (65%) of the target 560 pts were randomized (147 Canada, 144 Europe, 64 Australasia, 6 Japan). Median age of randomized patients is 73 (65-88) years. A planned futility analysis after 120 events by the independent DSMB resulted in a recommendation that the trial continue.Accrual is expected to be complete in 2013. A comprehensive molecular companion analysis, including MGMT promoter methylation, is planned.
Bevacizumab plus radiotherapy for elderly patients with glioblastoma (ARTE).
Authors: Tabatabai Ghazaleh , Weller Michael 
Published: March 2020

TPS2105 Background: The standard of care for patients with newly diagnosed glioblastomas after surgical resection is radiotherapy with concomitant and adjuvant temozolomide chemotherapy. Yet, inclusion into the pivotal trial was limited to patients up to the age of 70, and subgroup analyses suggested that older patients did not gain benefit from combined modality treatment. Further, the efficacy of radiotherapy has been confirmed in a randomized trial comparing best supportive care versus radiotherapy alone. Of note, hypofractionated radiotherapy is equieffective in patients aged 65-70 years and more. Two randomized trials in elderly patients (NOA-08, Nordic Trial) indicated smilar efficacy of primary temozolomide chemotherapy alone compared with radiotherapy alone. Combined radiochemotherapy is compared with radiotherapy alone in an ongoing NCIC-CTG EORTC TROG Japanese group trial 26062-22061. Thus, radiotherapy alone is the standard of care for newly diagnosed glioblastoma of elderly patients. These clinical data justify the exploration of new, temozolomide-free first-line treatment strategies in elderly patients. Methods: The ARTE trial will therefore investigate bevacizumab when added to a short course of radiotherapy and bevacizumab maintenance therapy until progression. The translational research program shall include blood and urine biomarker analysis and FET-PET in addition to MRI for monitoring the course of the disease. This trial is an explorative randomized, non-comparative phase II trial aiming at recruiting 60 patients in Switzerland. Elderly patients (> 65) will be randomized 2:1 either to the experimental arm (bevacizumab plus radiotherapy) or the standard arm (radiotherapy). The primary endpoint is median overall survival. Secondary endpoints include overall survival at 6 months, overall survival at 12 months, median progression-free survival, progression-free survival at 6 months, median time to treatment failure.
Phase III trial of tumor-treating fields (TTFields) together with temozolomide compared with temozolomide (TMZ) alone in patients with newly diagnosed glioblastoma multiforme (NCT00916409).
Authors: Kesari Santosh , Taillibert Sophie , Kanner Andrew , Weinberg Uri ,   on behalf of the EF-14 Study Investigators
Published: March 2020

TPS2106 Background: TTFields therapy is a novel, non-invasive, anti-mitotic treatment, inhibiting tumor growth by interfering with the metaphase to anaphase transition during mitosis (Lee et al., 2011). TTF therapy was recently approved by the FDA for recurrent GBM following a prospective, randomized trial. Preclinical studies have shown TTFields and TMZ to have an additive inhibitory effect on glioma cell proliferation. The design for the current study was supported by results from a pilot study with TTFields therapy and TMZ in patients with newly diagnosed GBM demonstrating favorable safety, tolerability and promising efficacy (Kirson et al., 2009). Methods: The hypothesis of the current study is that the addition of TTFields therapy to maintenance TMZ will increase progression free survival (PFS) of newly diagnosed GBM patients. Secondary endpoints include overall survival (OS), radiological response, quality of life and safety. Eligible patients will be randomized (2:1) to continuous TTFields therapy (200 kHz) in combination with maintenance TMZ versus maintenance TMZ alone. Maintenance TMZ will be administered as per the Stupp Protocol for 6 courses (Stupp et al., 2005). TTFields therapy may be administered for up to 24 months. Patients will be stratified based on: extent of resection and MGMT methylation status. Eligibility criteria include: pathological diagnosis of GBM; Karnofsky ≥ 70; previous chemoradiotherapy per Stupp Protocol; no progressive disease at baseline. Patients with infratentorial tumor or implanted electronic devices are excluded. The sample size of 700 patients will have 80% power to detect a 2 month (9 vs 7 months) improvement in PFS using log-rank test with an overall 5% 2-sided type I error. The trial is also powered to detect a 4.5 month increase in median OS in NovoTTF-100A/TMZ patients. Patients will be followed clinically monthly and with bimonthly MRI to assess tumor progression and additional endpoints. 221 patients have been enrolled at the time of abstract submission. The DMC last reviewed the trial in October 2010 and recommended that the trial continue as designed.
A randomized, double‑blind, controlled phase IIb study of the safety and efficacy of ICT‑107 in newly diagnosed patients with glioblastoma multiforme following resection and chemoradiation.
Authors: Hawkins Elma S. , Aiken Robert , Chandler James , Fink Karen L. , Glantz Michael J. , Grewal Jai , Gruber Michael L. , Kesari Santosh , Landolfi Joseph C. , LaRocca Renato V. , Lesser Glenn Jay , Markert James , Mayer Tina M. , O'Rourke Donald , Peereboom David M. , Phuphanich Surasak , Schiff David , Sloan Andrew E. , Stea Baldassarre , Zhu Jay-Jiguang 
Published: March 2020

TPS2107 Background: Tumor stem cells have been correlated with recurrence and clinical outcome in glioblastoma multiforme (GBM). ICT‑107 is an autologous vaccine consisting of the patient’s dendritic cells pulsed with 6 synthetic peptide CTL epitopes targeting the GBM tumor and tumor‑stem cell associated antigens MAGE‑1, HER‑2, AIM‑2, TRP‑2, gp100 and IL‑13Rα2. Phase I results showed a good safety profile and interesting clinical potential (ASCO, 2010, abs#2097 and ASCO, 2011, abs#2042) in 16 newly diagnosed GBM patients with a median progression-free survival (PFS) of 16.9 months (measured from surgery) and a median overall survival (OS) of 38.4 months. Methods: In this Phase II study eligible patients have newly diagnosed GBM and complete surgical resection or minimum residual tumor < 1 cm3, are HLA-A1 and/or HLA-A2 positive, older than 18, have Karnofsky Performance Score (KPS) of ≥ 70% and have adequate hematologic and chemistry parameters. Patients with a serious immune or autoimmune disorder or other systemic disease are excluded. Patients undergo apheresis to isolate peripheral blood mononuclear cells (PBMCs) to be used for preparation of study treatment (ICT‑107 and Control). Pre-study treatment consists of 6 weeks of concurrent temozolomide (TMZ) and radiation. After stratification by site and age, patients are randomized 2:1 to receive either ICT-107 or its matching control (autologous, unpulsed dendritic cells). Patients then receive induction ICT-107 or control once a week for four weeks. All patients subsequently receive maintenance TMZ for 5 days per month for 12 months. Booster vaccinations occur at Cycles 1, 3, 6 and 10, and every six months thereafter. The primary endpoint is OS and secondary endpoints include PFS, rates of OS and PFS at 6 months after surgery and every 3 months thereafter, safety and tolerability of ICT‑107, immune response to ICT-107 and predictors of response. 120 patients have been enrolled in this ongoing trial. It is expected that approximately 200 patients will be enrolled for screening with the intention to randomize at least 102 patients. The trial significance is alpha=0.025 one-sided.
Phase Ia/b study of combination carboplatin, paclitaxel, and ridaforolimus in patients with solid, endometrial, and ovarian cancers.
Authors: Chon Hye Sook , Lee Ji-Hyun , Herschberger Amber B , Wenham Robert M 
Published: March 2020

TPS3114 Background: mTOR is a member of the PI3K family. Ridaforolimus (RIDA) is a mTOR inhibitor that has demonstrated tolerability as intravenous (IV) and oral formulations. PI3K/AKT/mTOR signalling is associated with resistance to taxanes. In cancer (ca) cells, inhibition of mTOR signalling counteracts AKT-mediated resistance to drugs inhibiting tubulin. Paclitaxel and carboplatin (PC) have broad activity including endometrial, ovarian, and many cancers. mTOR inhibition with PC has synergistic and additive effects in solid tumors. A common defect in endometrioid ca is mutation of PTEN, causing activation of the PI3K/AKT/mTOR pathway. RIDA improved PFS over hormonal therapy of metastatic endometrial cancer in a randomized phase II study (Oza AM, et al. J Clin Oncol. 2011;29 [suppl; abstr 5009]). In 35 patients in a phase II study of RIDA, there were 7.7% partial response (PR) and 58% with stable disease with median duration 6.6 months (Mackay H et al. J Clin Oncol. 2011;29 [suppl; abstr 5013]). Ovarian ca ultimately develops a phenotype resistant to taxanes that may be overcome with mTOR inhibition. RIDA may therefore potentiate the response of endometrial, ovarian, and other solid cancers to PC. Methods: Patients (pts) with advanced solid ca and measureable disease and up to 3 prior therapies received P (175mg/m2 IV) and C (AUC 5 to 6 mg/ml/min IV) on day (D)1 of each 3-week cycle. RIDA in escalating cohorts of 10-40 mg is administered orally daily for 5 days per week (D1-5, D 8-12, D 15-19) in phase IA cohorts. Samples for pharmacokinetics of RIDA and P and pharmacodynamics (PD) are collected. More than 1 anticipated DLT of thrombocytopenia or neutropenia in the latter part of the cycle shifts the escalation of RIDA to an alternate schedule (D1-5, D 8-12). Escalation continues in a 3X3 design until 40 mg/day of RIDA or MTD. Seven pts have been enrolled; 5 ovarian, 1 endometrial, 1 urethral ca. The second cohort of an alternate schedule has been filled and evaluation continues. Further characterization of tolerability, efficacy, and PD are planned at the MTD in the phase IB expansion cohorts of 15 ovarian/15 endometrial cancers.
BARIS: A phase I trial to evaluate the safety and tolerability of combined BIBF 1120 and RAD001 in solid tumors and to determine the maximum tolerated dose (MTD) of the combination.
Authors: Scheffler Matthias , Nogova Lucia , Gardizi Masyar , Bos Marc Christiaan Allardt , Papachristou Irini , Sos Martin , Zander Thomas , Mattonet Christian , Wolf Juergen 
Published: March 2020

TPS3115 Background: Simultaneious inhibition of several signallingpathways involved in angiogenesis as well as in tumor cell growth regulation by kinase inhibitor combination therapy may increase therapeutic efficacy. Here we evaluate the combination of the mTOR-inhibitor RAD001 (everolimus) and the triple kinase (FGFR, VEGFR, PDGFR) inhibitor BIBF 1120in a phase I trial in advanced solid tumors.In addition we use DCE-MRI for early identification of patients with benefit from BIBF 1120. Methods: This is an open-label, monocentric phase I trial with three dosage arms in a classical "3+3" design: Patients in arm A receive 5 mg of RAD001 and 2 x 150 mg BIBF 1120, in arm B 10 mg RAD001 and 2 x 150 mg BIBF 1120 will be administered, whereas in arm C, 10 mg of RAD001 and 2 x 200 mg BIBF 1120 will be given. There is no interindividual dose escalation, and the enrollment of the patients will be performed sequentially. Eligible are all patients with relapsed or refractory advanced/metastatic solid tumors (UICC stage IV) and an ECOG performance state of 0-1 for whom no further standard therapies are available and who have predefined adequate organ functions. All patients will start with a 2-week run-in phase of 2 x 200 mg BIBF 1120. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scans will be performed at baseline staging, on day 3 and day 14. On day 14, there will also be 12 hours-pharmacokinetic (PK) assessment. Combination therapy within the forementioned dosage arms starts on day 15. After two weeks of combination therapy, on day 29, a DCE-MRI scan and 12-hours PK will be performed. Restaging for the evaluation of the efficacy will be performed on day 57. The safety of this combination will be assessed throughout the complete therapy phase using CTC-AE V4.0, with predefined dose-limiting toxicities (DLTs) being assessed until day 42. Patients who experience clinical benefit (i.e., response or stable disease) on day 57 with adequate tolerability of the combination will further receive the medication, as long as the benefit lasts. The trial is registered under NCT01349296 (clinicaltrials.gov). Recruitment in arm A has started in February 2012.