bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vinflunine maintenance therapy versus best supportive care (BSC) after platinum combination in advanced bladder cancer: A phase II, randomized, open-label study (MAJA study)—SOGUG 2011-02.
Authors: Maciá Sonia , Garcia-Donas Jesus , Font Pous Albert , Domenech Montserrat , Garcia del Muro Xavier , Mellado Begoña , Puente Javier , Arranz Arija Jose Angel , Climent Duran Miguel Angel , Lainez Milagro Nuria , Perez-Gracia Jose Luis , Gonzalez del Alba Aranzazu , Villa Guzman José Carlos , Pérez-Valderrama Begoña , Echaburu Juan Virizuela , Bonfill Teresa , Leon Mateos Luis , Morales-Barrera Rafael , Castellano Daniel E. , Bellmunt Joaquim ,   Spanish Oncology Genitourinary Group (SOGUG)
Published: March 2020

TPS4674 Background: Vinflunine is a novel microtubule inhibitor currently approved by EMA as treatment after platinum progression, in metastasic bladder cancer. It is distinguished from the other vinca-alkaloids because it binds relatively weakly to tubulin, suggesting an improved tolerance profile as a result of less neuropathy. Based on the fact that no cumulative toxicity is expected and the results reported in second-line, we aim to test the role of vinflunine in first line therapy, as maintenance treatment for patients who obtain clinical benefit after platinum. Methods: This is a multicenter, randomized, open label, proof-of-concept study that will be performed in 20 institutions members of the Spanish Oncology Genitourinary Group (SOGUG). Subjects will be randomized in a 1:1 ratio to receive vinflunine 320 mg/m2 every 21 days plus BSC vs BSC alone until disease progression. Vinflunine dose will be 280mg/m2 for patients with PS=1, age ≥ 75 years, prior pelvic radiotherapy or creatinine clearance Cr <60ml/min. Stratification factors are: 1) Scheduled dose at randomization (320 vs 280mg/m2) 2) Liver metastasis (Y/N). Main inclusion criteria are: Subjects ≥18 and< 80 years of age with histological diagnosis of transitional cell carcinoma of the urothelial tract and measurable disease with radiological response or stabilization after 6 cycles of a platinum containing doublet for metastasic/advanced disease. Primary objective will be progression free survival (PFS), considering as clinically relevant 6 months in experimental arm. To guarantee an overall type-1 α error (one side) no greater than 0.05 and a type II (β) error 0.1 for the primary endpoint of PFS, a sample size of 86 patients allocated in a 1:1 ratio is planned. Recruitment is scheduled to start by February 2012. A pharmacogenomic translational study will also be conducted.
Phase II study of everolimus (E) in refractory germ cell tumors (GCTs).
Authors: Mego Michal , Svetlovska Daniela , Obertova Jana , Reckova Maria , Miskovska Viera , Rajec Jan , Sycova-Mila Zuzana , Palacka Patrik , Liskova Stefania , Chovanec Michal , Salek Tomas , Mardiak Jozef 
Published: March 2020

TPS4677 Background: GCTs represent a model for the cure of cancer. Nonetheless, a small proportion of patients (pts) develop disease recurrence. Because of insufficient results in the treatment of relapsed GCTs, evaluation of new treatments is a priority. Loss of the tumor suppressor gene PTEN (phosphatase and tensin homolog) marks the transition from intratubular germ cell neoplasias (ITGCN) to invasive GCTs. In the testis, PTEN was abundantly expressed in germ cells whereas it was virtually absent from 56% of seminomas as well as from 86% of embryonal carcinomas and virtually all teratomas. On the contrary, ITGCN intensely expressed PTEN, indicating that loss of PTEN expression is not in early event in GCTs development, but is associated with disease progression. PTEN inactivation is associated with dysregulation of PI3K/Akt pathway and increased mTOR signalling. We hypothesize that dysregulation of PI3K/Akt pathway due to PTEN inactivation in GCTs suggests that these pts could have greater benefit from mTOR inhibition. Methods: In December 2011, National Cancer Institute of Slovakia launched an one arm, two-staged phase II study aimed to evaluate the efficacy and toxicity of E in pts with refractory GCTs. The primary objective is to determine the efficacy of E in patients with refractory GCTs. Secondary objectives includes favourable response rate, time to progression and safety. The pts with radiological and/or serological proof of relapsed GCTs, who were not amenable to be cured by chemotherapy or surgery and who failed at least two platinum-based regimens or one platinum regimen in case of platinum-refractory disease or primary mediastinal non-seminomatous GCTs were eligible. All other standard inclusion and exclusion criteria for study of salvage treatment in refractory GCTs pts were applied. E will be administered at a dose of 10mg daily until progression or unacceptable toxicity. Assuming a response rate of clinical interest of ≥40%, a minimal response rate of 20%, a probability of 5% for rejecting an active drug, and a probability of 20% to further evaluate an ineffective drug, 18 pts will be enrolled into the first cohort. If <4 responses will be observed, the study will be terminated, otherwise, it will be continued with a second cohort of 20 pts.
A phase II study of intermittent sunitinib in previously untreated patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Wood Laura S. , Dreicer Robert , Garcia Jorge A. , Gilligan Timothy D. , Ali Khaled B. , Haddad Housam , Shah Shetal N. , Elson Paul , Rini Brian I. 
Published: March 2020

TPS4684 Background: Sunitinib is a standard of care initial treatment in mRCC. One challenge is balancing the acute and chronic toxicity of therapy with clinical benefit. Pre-clinical and retrospective clinical data support the concept that treatment breaks are feasible and not associated with a reduction in efficacy of sunitinib. It is hypothesized that an intermittent dosing regimen of sunitinib in mRCC pts is feasible, and may lead to prolonged duration of disease control with improved tolerance. Methods: Eligibility criteria include treatment-naïve clear cell mRCC, measurable disease, and adequate organ function. Pts will be treated for 4 cycles of sunitinib (50 mg 4/2) in the absence of unacceptable toxicity or RECIST-defined progression. Pts with ≥ 10% reduction in tumor burden per RECIST following 4 cycles will have sunitinib held, with re-staging CT scans approximately every 10 weeks thereafter to assess tumor burden. Sunitinib will be re-initiated in those patients with an increase in tumor burden of 10% or greater (per RECIST) compared to the scan obtained just prior to holding sunitinib. Pts who have RECIST tumor burden reduction of 10% or more compared to scans at the start of the most recent treatment period will again have sunitinib held. This intermittent sunitinib dosing will continue until RECIST-defined disease progression while on sunitinib. Patients not initially achieving at least a 10% reduction in tumor burden will continue sunitinib. The primary objective is the feasibility of intermittent sunitinib, defined as the proportion of patients eligible for and who undergo intermittent therapy. The alternative hypothesis is a feasibility rate of > 80% vs. the null hypothesis of < 50%. Thirty pts provides 80% power based on a two-sided exact test with a .05 type I error. Secondary endpoints include PFS and toxicity. Twenty five of planned 30 patients have been enrolled.
Prospective assessment of circulating endothelial cells (CECs) as early markers of clear cell renal cell carcinoma (CCRCC) progression in first line setting: The Circles study (SOGUG 2011-01).
Authors: Castellano Daniel E. , Esteban Emilio , Leon Luis , Basterretxea Laura , Gonzalez Arancha , Mendez Maria Jose , Jimenez Paula , Maroto Pablo , Garcia del Muro Xavier , Arranz Jose Angel , Climent Miguel Angel , Garcia-Donas Jesus 
Published: March 2020

TPS4685 Background: Since the identification of Von Hippel Lindau (VHL) gene mutations as a critical step in the development of most Clear Cell Renal Cell Carcinomas (CCRCC), neoangionesis inhibition has become a cornerstone in their treatment. Despite the proven efficacy of antiangiogenic drugs, most patients will not achieve partial response by RECIST criteria. Thus, to accurately determine tumor progression is a challenging question incompletely answered by traditional radiological assessment. In recent years CECs counts have been proposed as surrogate biomarkers of angiogenesis that could be used for monitoring tumor evolution while on targeted therapies. We aim to figure out if CECs elevations could anticipate radiological progression in CCRCC. Methods: An observational prospective study is being performed in 10 institutions members of the Spanish Oncology Genitourinary group (SOGUG). Patients older than 18 years with histologically proven CCRCC on first line treatment with any targeted drug who have not progressed after 3 months of therapy are considered elegible. Recruitment begun on August the 1st 2011 and 15 of the 75 scheduled patients have been included so far. CECs are periodically collected in peripheral blood every 6 weeks for 15 months or radiological tumor progression, whatever occurs first. Median CEC values will be calculated and stated by descriptive statistics (Cellsearch, VERIDEX). To explore the evolution of CECs counts along treatment a linear model will be constructed. An association among CECs counts changes and time to progression will be analyzed with Cox model.
TERRAIN: A randomized, double-blind, phase II study comparing MDV3100 with bicalutamide (Bic) in men with metastatic castrate-resistant prostate cancer (CRPC).
Authors: Baskin-Bey Edwina S. , Shore Neal D. , Barber Kenya , Ouatas Taoufik , Heidenreich Axel 
Published: March 2020

TPS4698^ Background: MDV3100 is a novel androgen receptor (AR) signaling inhibitor (ARSI) in clinical development for treatment of prostate cancer (PCa). Compared with Bic in nonclinical CRPC models, MDV3100 showed higher affinity AR binding, inhibited nuclear translocation and AR-DNA binding, showed no evidence of AR agonism, and caused tumor regression in Bic-resistant xenografts. MDV3100 has shown antitumor activity in men with advanced PCa. We present the study design of a trial comparing MDV3100 and Bic in men with progressive metastatic PCa. Methods: Multinational study (Table) with planned enrollment of 370 patients (randomized 1:1 to MDV3100 160 mg/d or Bic 50 mg/d). Inclusion criteria include metastatic (≥2 bone lesions or soft tissue disease at screening) progressive CRPC (≥3 rising prostate-specific antigen [PSA] levels or new bone/soft tissue disease), ongoing stable gonadotropin-releasing hormone (GnRH) analog therapy or surgical castration (serum testosterone <50 ng/dL), Eastern Cooperative Oncology Group performance status 0–1, and life expectancy ≥1 year. Exclusion criteria include previous chemotherapy, current/prior antiandrogens (except if administered for <12 wk and discontinued no less than 6 mo before study). Patients will be stratified by time of bilateral orchiectomy or GnRH analog initiation (before/after diagnosis of metastases) and will receive treatment until occurrence of radiographic progression/skeletal-related event, start of new antineoplastic therapy, or development of an adverse event requiring discontinuation. Results: The primary endpoint is progression-free survival; secondary endpoints are safety, PSA response, and time to PSA progression. Exploratory endpoints include circulating tumor cell conversion rate and quality of life. Patients are currently enrolling. Conclusions: This ongoing, head-to-head, phase II trial is the first to prospectively assess whether MDV3100 can provide improved antitumor effects vs Bic in men with metastatic CRPC. [Table: see text]
A phase II study of live-attenuated listeria monocytogenes immunotherapy (ADXS11-001) in the treatment of persistent or recurrent cancer of the cervix (GOG-0265).
Authors: Huh Warner King 
Published: March 2020

TPS5115 Background: This is a GOG/NCI sponsored phase II study (NCT01266460, GOG 0265) of ADXS11-001 in patients with persistent or recurrent cancer of the cervix. ADXS11-001 is a live attenuated Listeria monocytogenes (Lm) immunotherapy bioengineered to secret a HPV E7 fusion protein targeting HPV-E7 transformed cells. A previous phase I dose escalation study determined the safety of ADXS11-001 in patients with late stage cervical cancer (Maciag PA. Vaccine. 2009 Jun 18;27(30):3975-83). The primary objectives of this study are: to evaluate the tolerability and safety of ADXS11-001; and to assess the activity of ADXS11-001 in patients with persistent or recurrent cancer of the cervix. Secondary objectives are progression-free survival, overall survival and objective tumor response. Methods: Patient eligibility criteria: Females age ≥ 18 years with persistent or recurrent squamous or non-squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix with documented disease progression (disease not amenable to curative therapy). Patients must have measurable disease as defined by RECIST 1.1; at least one “target lesion” as defined by RECIST 1.1; have had one prior systemic chemotherapeutic regimen for management of their disease; have adequate organ function and must be free of active infection and not on antibiotics. This protocol is a Simon 2-stage design with a planned sample size of up to 67 patients. Patients will receive ADXS11-001 at a dose of 1x109 CFU on Day 1 and repeat every 28 days for 3 total doses in the absence of disease progression or unacceptable toxicity, with each dose followed at 72 hours by a 7 day course of ampicillin, 500 mg QID. Tumor tissue and serum samples may be collected periodically for translational research. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years. This phase II study just began enrolling and as of January 27, 2012, 2 patients have been enrolled.
LUX-H&N 1: A phase III, randomized trial of afatinib versus methotrexate (MTX) in patients (pts) with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed after platinum-based therapy.
Authors: Machiels Jean-Pascal H. , Licitra Lisa F. , Haddad Robert I. , Tahara Makoto , Svensson Liz , Cong Xiuyu Julie , Ehrnrooth Eva , Cohen Ezra E. W. ,   LUX-H&N1 Study Group
Published: March 2020

TPS5598 Background: EGFR (ErbB1) is expressed in 90% of HNSCC and associated with poor prognosis. Despite clinical benefit (CB) of EGFR-targeted treatments such as cetuximab treatment resistance will occur resulting in a need for novel targeted treatments to improve prognosis. Afatinib is an ErbB Family Blocker that irreversibly blocks signaling from all relevant ErbB Family dimers and may overcome limitations of current EGFR-targeted treatments in HNSCC. In a randomized, proof-of-concept, Phase II trial, afatinib demonstrated comparable anti-tumor activity to cetuximab in pts with R/M HNSCC progressing after platinum-based therapy (Seiwert TY, et al; THNO, November 2011; Abs 40). Methods: LUX-H&N 1 is a phase III, randomized, open-label trial (NCT01345682) evaluating efficacy and safety of afatinib vs. MTX in pts with R/M HNSCC who have progressed after platinum-based therapy. Key eligibility criteria: confirmed R/M HNSCC not amenable to salvage surgery/radiotherapy; documented PD after cisplatin and/or carboplatin for R/M disease; any other than 1 previous platinum-based regimen for R/M disease; ECOG status 0 or 1; no PD ≤3 months of completion of curatively intended treatment for locoregionally advanced or metastatic HNSCC; and no prior EGFR-targeted small molecules treatment. Eligible pts are stratified into four strata: ECOG performance score (0 vs. 1) and prior use of EGFR-targeted antibody therapy (Yes/No) given in the R/M setting. Pts are randomized 2:1 to: afatinib (40mg/d orally) or MTX (40mg/m2 IV weekly). Dose changes are permitted according to absence/presence of drug-related AEs (afatinib: escalation to 50mg/d and/or reduction to 40, 30 then 20mg/d; MTX: escalation to 50mg/m2 and/or reduction to 40, 30 then 20mg/m2). Pts receive continuous treatment until PD or AEs requiring withdrawal. Randomized treatment may continue beyond PD in case of CB as judged by the investigator. The primary endpoint is PFS and secondary endpoints include OS, OR, health-related QOL and safety. Target enrolment is 474 pts and completion of pt recruitment and data analyses are awaited.
WJOG6110B (ELTOP): Randomized phase II trial comparing trastuzumab plus capecitabine (HX) and lapatinib plus capecitabine (LX) in HER2-positive metastatic breast cancer patients previously treated with trastuzumab and taxanes.
Authors: Takano Toshimi , Kimura Hideharu , Nishio Kazuto , Yamanaka Takeharu , Ito Yoshinori , Fukuoka Junya , Tsurutani Junji , Shigeoka Yasushi , Uehara Masahiro , Sato Kazuhiko , Nakamura Shinichiro , Nakanishi Yoichi , Saeki Toshiaki ,   West Japan Oncology Group
Published: March 2020

TPS659 Background: In patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab and taxanes, there are now two standard strategies: trastuzumab beyond progression or switch to lapatinib. A randomized trial comparing trastuzumab plus capecitabine (HX) and capecitabine alone (X) after first-line trastuzumab-based chemotherapy (GBG-26) showed that HX was superior to X in terms of time to progression (TTP). Another randomized trial comparing lapatinib plus capecitabine (LX) and X in patients previously treated with anthracyclines, taxanes, and trastuzumab (EGF100151) showed that LX was superior to X in terms of TTP. To evaluate which strategy is better, we are conducting an open-label, randomized phase II trial comparing HX and LX. Methods: Primary endpoint is progression-free survival, and secondary endpoints are overall response rate, overall survival, proportion of patients progressing brain metastases as site of first progression, and safety. Major eligibility criteria include: (1) HER2-positive MBC, (2) previously treated with taxanes, (3) disease progression or distant relapse while receiving trastuzumab, (4) previously untreated with capecitabine, S-1, and anti-HER2 drugs other than trastuzumab, (5) previously treated with no more than two chemotherapy regimens for MBC, (6) no symptomatic brain metastases (asymptomatic brain metastases are allowed), and (7) baseline left ventricular ejection fraction ≥50%. Patients in the HX arm receive capecitabine 2,500 mg/m2/day on days 1 to 14 plus trastuzumab (8 mg/kg loading dose and 6mg/kg thereafter) on day 1 every 3 weeks. Patients in the LX arm receive capecitabine 2,000 mg/m2/day on days 1 to 14 plus lapatinib 1250 mg/day on days 1 to 21 every 3weeks. Large-scale biomarker analyses are also performed to explore predictive factors of trastuzumab or lapatinib efficacy. We are investigating biomarkers related to HER family and other receptors, PI3K/Akt pathways, ligands, FcγR, circulating tumor cells, and so on. This study has just begun and 7 of planned 170 patients have been enrolled.
MDV3100-08: A phase I open-label, dose-escalation study evaluating the safety, tolerability, and pharmacokinetics of MDV3100 in women with incurable breast cancer.
Authors: Elias Anthony D. , Richer Jennifer K. , LoRusso Patricia , Peterson Amy C. , Steinberg Joyce Leta , Mordenti Joyce , Lopez Christian , Hudis Clifford , Traina Tiffany A. 
Published: March 2020

TPS668 Background: MDV3100 is a novel, orally administered small molecule that directly binds the androgen receptor (AR) to potently inhibit AR-mediated signaling via three mechanisms: inhibition of androgen binding to AR; inhibition of AR nuclear translocation; and inhibition of nuclear AR association with DNA. MDV3100 is not known to agonize AR signaling, can be taken without prednisone, and demonstrated an overall survival benefit in post-docetaxel prostate cancer at 160 mg/day. AR expression is observed in ~70% of all breast cancer (BCa) regardless of histologic subtypes (estrogen receptor [ER] positive, HER2+, and triple negative [TN] disease). MDV3100 has demonstrated preclinical activity in AR+/TN and AR+/ ER+ BCa and could be a potential therapeutic strategy in patients with AR+ BCa. Methods: This Phase 1 study has 2 stages: a standard 3+3 dose-escalation stage (S1), evaluating safety, tolerability, and pharmacokinetics (PK) of MDV3100, starting at 80 mg MDV3100; and a dose-expansion stage (S2), evaluating the recommended Phase 2 dose in ~15 women with AR+ BCa. All patients must have received ≥2 chemotherapy-containing regimens for their incurable BCa, or ≥3 anti-HER2 containing regimens for their incurable HER2+ BCa to be eligible; ER+ patients must be post-menopausal. In S1, patients will receive their assigned dose of MDV3100 on Day 1, and PK samples will be collected through Day 8. Daily dosing will begin on Day 8 and will continue until predefined discontinuation criterion is met. Dose-limiting toxicities will be recorded through Day 35 and used to determine the Phase 2 dose. Extensive PK sampling is performed on Days 1 and 50 with predose PK samples collected throughout. In S2, patients with AR+ BCa (defined as 10% or more tumor cells with nuclear AR expression) will take daily MDV3100 at the recommended Phase 2 dose; there is no single dose PK period. Tumor tissue submission is mandatory in S2. Safety and tolerability will be documented by frequent assessments of adverse events, vital signs, and laboratory assessments. Tumor assessments occur at 2 months then approximately every 3 months thereafter. Enrollment of 27 subjects is anticipated.
Aromatase inhibitors, arthralgias, and exercise in breast cancer survivors.
Authors: Irwin Melinda , Cartmel Brenda , Ercolano Elizabeth , Fiellin Martha , Rothbard Marianna , Capozza Scott , Zhou Yang , Schmitz Kathryn , Ligibel Jennifer A. , Hershman Dawn L. , Neogi Tuhina , Gross Cary P. 
Published: March 2020

TPS669 Background: A substantial number of breast cancer survivors who are taking aromatase inhibitors (AIs) complain of side effects including arthralgias. Given the efficacy of AIs, it is essential that we identify approaches to mitigate arthralgias. We are conducting an NCI-funded trial is to examine the impact of a year-long exercise intervention in 180 breast cancer survivors taking an AI and experiencing at least mild arthralgias. Outcomes include severity of arthralgias, endocrine-related quality of life, % body fat, bone mass, and serum markers of inflammation. The purpose of this abstract is to present preliminary recruitment and adherence results. Methods: Women are being recruited via the Connecticut Tumor Registry and Rapid Case Ascertainment Shared Resource of Yale Cancer Center into the Hormones and Physical Exercise (HOPE) Study. Participants are randomly assigned to exercise (n = 90) or usual care (n = 90). The exercise intervention includes supervised resistance and unsupervised aerobic exercise sessions over 12 months. Data are collected at baseline, 3-, 6-, 9 and 12-months. Results: Study recruitment began in April 2010 and will continue through December 2012. As of January 1, 2012, we have received 1605 names of potentially eligible women. Of these 1605, 777 women are waiting to be screened (e.g., letter mailed to patient or on hold because recently diagnosed), 244 women could not be screened (e.g., unable to contact by phone), and 584 women have completed a telephone screening. Of the 584 women screened, 24% were ineligible because of discontinuing AIs because of arthralgias or chose not to take AIs primarily because of this potential side effect; another 36% were ineligible for various reasons; 24% were not interested; 11% were randomized (n = 65 women); and 5% are undergoing baseline visits (n = 29). On average, women are 62 yrs old and have been taking an AI for 1.8 yrs. Twenty-three women have completed the trial, with high exercise adherence rates (attendance to supervised sessions = 82% ). Conclusions: A growing number of women are choosing to not take AIs or are discontinuing AIs because of side effects. Our study may prove beneficial for the growing number of women diagnosed with hormone receptor-positive breast cancer each year.