bluuebunny/crossref_metadata_2025_split huggingface dataset:
The MIRACLE trial: A randomized, controlled trial comparing green tea extract versus placebo for the prevention of metachronous colon adenomas in a screening population.
Authors: Ettrich Thomas , Stingl Julia , Muche Rainer , Berger Andreas , Seufferlein Thomas 
Published: March 2020

TPS1612 Background: Prevention of colorectal cancer is a major health care issue. After polypectomy there is an increased risk of polyp recurrence and various means of chemoprevention have been tried to prevent this. NSAIDs have been shown to be effective but confer side effects such as gastrointestinal bleeding. Nutraceuticals such as polyphenols from tea plants have demonstrated remarkable therapeutic and preventive effects in molecular, epidemiological and some clinical trials. However, their value in preventing colorectal polyps has not been demonstrated in a large, randomized trial. The beneficial safety profile of decaffeinated green tea extract and accumulating evidence of its cancer preventive potential justify and require, in our view, a validation of this compound for the nutriprevention of colorectal adenoma. Good accessibility and low costs might render this neutraceutical a top candidate for wider use as nutritional supplement in colon cancer prevention. Methods: Randomized, double blinded, placebo-controlled, multicenter trial. After a one month run-in period with verum, 2534 patients (age: 50-80 years) who have undergone polypectomy within the last 6 months will be randomized to receive either decaffeinated green tea extract (containing 150 mg epigallocatechin gallate (EGCG) two times daily) or placebo over a period of three years. 2028 patients are expected to complete the whole study course. Primary outcome: Incidence of metachronous colorectal adenomas (tubulovillous, tubular, villous, serrated lesions) at the 3 year follow-up colonoscopy Secondary outcomes: Occurrences, number, localization, size and histological subtypes of adenomas, frequency of colorectal carcinoma. In addition, genetic and biochemical biomarkers in blood samples and genetic alterations (e.g. K-ras, B-raf, specific microRNAs) in tissue samples of adenomas will be analyzed (biobanking subprojects). Additionally, nutrikinetics and nutrigenetics of EGCG and other catechins will be assessed in healthy volunteers. Patient recruitment has started in November 2011. We expect the last patient out in fall 2017. (Trial identifier: NCT01360320)
Mitigation of iatrogenic risk in young women Hodgkin’s survivors, acceptability of a structured information process.
Authors: Eisinger François , Boyer-Chammard Agnes , Gonzague Laurence , Coso Diane , Viens Patrice , Bouabdallah Reda 
Published: March 2020

TPS1613 Background: Long term follow up of cancer survivors uncovers iatrogenic risk. Higher risk for second cancers should be mainly observed for cancer with a high rate of therapeutic efficacy, using aggressive therapeutic and for cancers occurring in young people. Hodgkin lymphoma fits all these criteria. Consistent data about higher risk for breast cancer in these women had been published. However, risk management is not yet often carried out. Methods: We plan to carry out a national program aiming both at offering counselling and screening protocol and to assess key parameters allowing to better estimate risk, and offering acceptable and effective risk management option. Our National program will start in January 2013. We are now in a pilot phase in a single medical institution in which we offered women previously affected with an Hodgkin lymphoma to have access to risk analysis and information and if they agree to a specific breast cancer screening program. We present some of our psychosocial questionnaire analysis based on 27 women (aged 19-50 years old) fulfilled at the end of the information consultation and one month latter. Results: There was few or no negative assessment: no one stated that they express regrets to have been informed, nor they better ignore some delivered information, no one feel that risk management description is unsatisfying and no one will advice an other women against that kind of consultation. Only 4 out 27 i.e. 15% stated that there was in delivered information a source for anxiety. However positive assessment was only fairly high and not stable after one month. Information process to inform women survivors from Hodgkin lymphoma of their higher risk of being affected with a breast cancer and the current recommendation for earlier breast cancer screening reach a high level of satisfaction at the initial stage of the process. However it could decrease with time and thus, need to be monitored. [Table: see text]
Vorinostat to restore sensitivity to aromatase inhibitor therapy in metastatic breast cancer: A phase II clinical trial with ER imaging correlates.
Authors: Linden Hannah M. , Kurland Brenda F , Link Jeanne , Gadi Vijayakrishna K. , Specht Jennifer M. , Gralow Julie , Schubert Erin K , Peterson Lanell , Eary Janet F. , Mankoff David A. 
Published: March 2020

TPS3109 Background: Endocrine refractory,Indolent, soft tissue, and bone dominant metastatic breast cancer is a clinical problem, for which alternatives to chemotherapy are needed, Histone deacetylace inhibitors (HDACi) have shown pre-clinical promise in estrogen receptor-modulation and restoring sensitivity to endocrine manipulation, suggesting potential clinical benefit. HDACi restore ER expression in ER-negative cells which are then sensitive to AI treatment in xenografts (Sabnis 2011) and are toxic to ER-positive cell lines (Huang 2000). Vorinostat is an FDA approved HDACi for CTCL, and could have a beneficial role in restoring ER-signaling in endocrine-resistant tumors. We hypothesized that HDACi therapy could restore sensitivity to aromatase inhibitor (AI) therapy, in patients with prior progression on AI, and allow continued endocrine therapy. Recent data suggest clinical benefit of Tamoxifen and vorinostat given continuously (Munster 2011) as well as entinostat and an AI (Yardley 2011). Our prior work has shown the feasibility of monitoring regional ER expression and ER-estrogen binding in vivo using [F-18]fluoroestradiol (FES) PET imaging (Linden 2011) providing a biomarker to interrogate the molecular target. Methods: Patients with metastatic breast cancer with prior clinical benefit from endocrine manipulation who progressed on AI therapy are eligible. Patients must be off ER blocking therapies, and functionally postmenopausal. Baseline FES and FDG PET are performed and patients receive investigational vorinostat treatment at 400 mg po BID for 2 weeks followed by serial FES and FDG PET to assess the impact of vorinostat on ER expression and tumor metabolism. Patients are retreated on their prior AI as a single agent for 6 weeks, followed by paired FES and FDG and clinical assessment. Patients with clinical benefit may continue on treatment: 2 weeks of vorinostat followed by 6 weeks of AI in 8-week cycles until progressive disease or toxicity. We have enrolled 4 of a planned 20 patients.
First-in-human phase I clinical trial of QBI-139, a human ribonuclease variant, in solid tumors.
Authors: Strong Laura E. , Kink John A. , Mei Baigen , Shahan Mark N. , Raines Ronald T. 
Published: March 2020

TPS3113 Background: RNA has been recognized as a drug target for cancer therapy, as evidenced by the ongoing clinical trials of RNAi and antisense therapies. An alternative approach that circumvents the delivery and stability issues of RNAi and antisense is to harness the activity of naturally occurring enzymes that degrade RNA. Variants of human ribonucleases (RNase) have been generated with diminished binding to their natural inhibitor inside cells, which allows the new proteins to kill cancer cells. QBI-139, a variant that retains 95% sequence identity to a naturally occurring RNase, has demonstrated efficacy as both a single agent and in combination against multiple tumor types in in vivo models of human cancer. A first in human phase I trial was designed and initiated for QBI-139. Methods: Since QBI-139 showed efficacy against multiple cancers in model systems, a first in human phase I trial was designed for patients with advanced solid tumors (NCT00818831). Patients receive QBI-139 by intravenous infusion once weekly for a cycle of three weeks. In the absence of disease progression or unacceptable toxicity, treatment can continue on the twenty one day cycle. The trial is a standard 3+3 design with cohorts of three to six patients receiving escalating doses of QBI-139 until the maximum tolerated dose (MTD) and/or recommended phase II dose is determined. The inclusion/exclusion criteria are typical for the patient population. Forty three patients have been treated to date (January 2012) without identification of dose limiting toxicity. The starting dose in the clinical trial was 3 mg/m2 while the most recently completed cohort was treated with a dose of 50.4 mg/m2. Dose escalation is ongoing. The primary outcome is to evaluate the toxicity and tolerability of QBI-139 in patients with advanced refractory solid tumors. This information will allow for identification of the maximum tolerated dose. Clinical exposure levels are being monitored by measuring the pharmacokinetics of QBI-139. Tumor response to QBI-139 will be measured using RECIST criteria. Since QBI-139 demonstrated broad efficacy in model systems, another outcome of the phase I trial may be identification of the indications for the next stage of clinical development.
A phase III, multicenter, randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine (G) as first-line therapy for metastatic adenocarcinoma of the pancreas: The GAMMA trial.
Authors: Fuchs Charles S. , Azevedo Sergio Jobim , Carrato Alfredo , Haddad Vincent , Lipton Lara Rachel , McGreivy Jesse S. , Moore Malcolm J. , Okusaka Takuji , Riess Hanno , Szczylik Cezary , Van Laethem Jean-Luc 
Published: March 2020

TPS4135 Background: Ganitumab (AMG 479) is an investigational, fully human, monoclonal antibody inhibitor of the IGF1R. In a randomized phase II study in patients with metastatic pancreatic cancer, addition of ganitumab 12 mg/kg every 2 weeks (Q2W) to G prolonged progression-free survival (PFS) and overall survival (OS) (Kindler. Ann Onc. 2010;21:741P). Exposure-efficacy analysis showed that patients with higher ganitumab exposure levels (AUCss at or above median) had longer PFS and OS (Lu. JCO. 2011;29:4049). Methods: In this phase III study, patients are randomized 2:2:1 to placebo + G, ganitumab 12 mg/kg + G, or ganitumab 20 mg/kg + G. Patients receive ganitumab or placebo IV days (D) 1 and 15 and G 1000 mg/m2 IV D 1, 8, and 15 every 28 D. Patients receiving 20 mg/kg ganitumab are expected to achieve ganitumab levels above the median in phase 2. Key eligibility criteria: untreated metastatic adenocarcinoma of the pancreas; ECOG score 0 or 1; ≥ 18 years old; adequate organ function; and fasting (or non-fasting) glucose ≤ 160 mg/dL. The primary endpoint is OS. A log-rank test stratified by ECOG, presence of liver metastases, and geographic region will compare OS independently for each ganitumab arm at an overall one-sided 2.5% significance level for declaring superiority of ganitumab + G vs placebo + G. Key secondary endpoints include PFS, objective response, safety, and patient-reported outcomes. An additional objective is to define a subpopulation with improved OS based upon baseline levels of circulating biomarkers. Enrollment began in April 2011. As of January 23, 2012, 463 of 825 patients have been enrolled. The study is overseen by an independent data monitoring committee. Status: open. Supported by Amgen Inc. in collaboration with Takeda Global Research & Development Center, Inc.; ClinicalTrials.gov: NCT01231347.
An observational study of metastatic renal cell carcinoma patients prior to initiation of initial systemic therapy.
Authors: Plimack Elizabeth R. , Nemec Cheryl , Elson Paul , Suarez Cristina , Dorff Tanya B , Larkin James M. G. , McAleer Cecilia , Nuñez Isaac , Fisher Rosalie Anne , Rini Brian I. 
Published: March 2020

TPS4679 Background: The biology of metastatic RCC is extremely diverse, including a subpopulation of patients with indolent growth of metastases. Because of the acute and chronic toxicity and assumed non-curative nature of current systemic targeted therapy, a select subset of patients may be better served with initial surveillance. Such an approach may allow for deferral of systemic therapy to minimize overall treatment-related toxicity burden while maintaining treatment benefit. Methods: A prospective phase II trial is being conducted to characterize the clinical course of patients with mRCC who defer initial systemic treatment. Appropriate patients are selected by the treating physician based on an observed indolent growth pattern. As such, there is a 12 month window allowed between the first diagnosis of metastatic disease and study entry. Patients must be treatment-naïve, asymptomatic, with histologically confirmed mRCC and clinically-evident, measurable disease to be eligible. Radiographic assessment is performed at baseline, every 3 months for year 1, every 4 months for year 2, then every 6 months. The primary objective is to characterize the clinical outcome of patients on observation in terms of time to RECIST defined disease progression and time to initiation of systemic treatment. Secondary endpoints include measurement of disease-related symptoms and depression/anxiety using standardized questionnaires (FKSI-DRS and HADS), as well as correlative endpoints analyzing the immune response over time for which blood is being collected for immune assays (TH1/TH2 phenotype, Tregs). Pts remain on study until initiation of systemic therapy due to radiographic disease progression, development of disease-related symptoms, withdraw of consent or clinical change that renders the patient unacceptable for further observation. Local therapy (e.g. surgery, radiation) during the observation period is permitted. Currently, 29 patients have been accrued at 5 collaborating sites. The target accrual of 50 pts provides adequate power for the primary descriptive endpoint as well as 80% power to detect changes from baseline for the correlate endpoints based on a two-sided Wilcoxon signed rank test.
Phase III trial of dovitinib (TKI258) versus sorafenib in patients with metastatic renal cell carcinoma after failure of anti-angiogenic (VEGF-targeted and mTOR inhibitor) therapies.
Authors: Motzer Robert John , Porta Camillo , Bjarnason Georg A. , Szcylik Cezary , Rha Sun Young , Esteban Emilio , De Giorgi Ugo , MacKenzie Mary J. , Mainwaring Paul N. , North Scott , Sabbatini Roberto , Bodrogi Istvan , Kabbinavar Fairooz , Carteni Giacomo , Sternberg Cora N. , Vogelzang Nicholas J. , Shi Michael , Urbanowitz Gladys , Escudier Bernard J. 
Published: March 2020

TPS4683 Background: Standard first- and second-line treatments in metastatic renal cell carcinoma (mRCC) target the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) signaling pathways. However, signaling through other pathways, including the fibroblast growth factor receptor (FGFR) pathway, may account for tumor resistance to these standard therapies. Dovitinib (TKI258) is an oral FGF, VEGF, and platelet-derived growth factor (PDGF) receptor tyrosine kinase inhibitor, with IC50 values of ≈ 10 nM. In a phase II study of 59 RCC patients, many of whom had failed prior VEGF-targeted and mTOR inhibitor therapies, dovitinib (500 mg/day on a 5-days-on/2-days-off schedule) was well tolerated and demonstrated promising anti-tumor effects, with progression-free survival (PFS) of 5.5 months (Angevin et al, ASCO 2011). Methods: Approximately 550 patients from over 26 countries will be randomized 1:1 in this multicenter, open-label, randomized phase III trial (NCT01223027) to receive dovitinib (500 mg/day on a 5-days-on/2-days-off schedule) or sorafenib (400 mg twice daily). Eligible mRCC patients must have failed 1 VEGF-targeted therapy and 1 mTOR inhibitor (disease progression on or within 6 months of stopping the prior treatment). Patients will remain on study until disease progression, unacceptable toxicity, death, or discontinuation for any other reason. No treatment crossover is planned. The primary endpoint is PFS as determined by central radiology assessment according to RECIST v1.1, with evaluations performed every 8 weeks. Secondary endpoints include overall survival, overall response rate, safety, patient-reported outcomes, and pharmacokinetics. The pharmacodynamic effects of dovitinib on plasma/serum biomarkers will also be explored. The data monitoring committee last reviewed the trial on 20 December 2011 and recommended that the trial continue as planned. This is the first third-line randomized clinical trial in mRCC to evaluate a multitargeted inhibitor of FGFR.
CA184-043: A randomized, double-blind, phase III trial comparing ipilimumab versus placebo following a single dose of radiotherapy (RT) in patients (pts) with castration-resistant prostate cancer (CRPC) who have received prior treatment with docetaxel (D).
Authors: Drake Charles G. , Scher Howard I. , Bossi Alberto , van den Eertwegh Alfons JM , McHenry Brent , Fitzmaurice Thomas F. , Cuillerot Jean-Marie , Chin Kevin M. , Gagnier Paul , Fizazi Karim , Gerritsen Winald R. 
Published: March 2020

TPS4689 Background: Ipilimumab (Ipi), a fully human monoclonal antibody which blocks CTLA-4, augments antitumor immune responses. Ipi has shown antitumor effects in prostate cancer model systems and clinical activity (via prostate-specific antigen [PSA] declines and RECIST response) in Phase 1/2 investigations in CRPC, with a side effect profile reflective of its mechanism of action. Preclinical data suggest that RT given prior to CTLA-4 blockade may increase antitumor activity. Methods: In this study, pts with CRPC who have progressed during or after D are randomized 1:1 to receive either a single dose of bone-directed RT followed by Ipi 10mg/kg, or RT followed by placebo. Within 2 days of RT administration (up to 5 lesions at 8 Gy on a single day) patients receive their initial dose of Ipi/placebo; Ipi/placebo is then given every 3 weeks for a total of 4 doses. Eligible pts may continue to receive blinded study drug every 12 weeks until they meet treatment stopping criteria, withdraw consent, are lost to follow-up, or study closure. The primary endpoint is overall survival (OS). Secondary endpoints include progression-free survival, pain response, and safety. The study is designed to detect a 3.8 month difference (HR=0.76) in median OS with 90% power and 0.05 2-sided type one error. The enrollment goal is 800 randomized patients, with a single interim analysis for superiority of OS planned at 435 events at approximately 33 months from first patient first visit (ClinicalTrials.gov identifier: NCT00861614). [Table: see text] [Table: see text]
A study of autologous dendritic cell therapy targeting mucin-1 for treatment of patients with epithelial ovarian cancer in first remission.
Authors: Berek Jonathan S. , Goh Jeffrey C. , Gray Heidi J. , Fiorica James , Mason James R. 
Published: March 2020

TPS5113 Background: Cvac (Cvac) is an autologous dendritic cell immune stimulant targeting mucin-1 positive tumors. A phase IIa study demonstrated potential for treating mucin-1 positive epithelial ovarian carcinoma (EOC). A phase IIb study was designed to determine on a pilot basis if Cvac could demonstrate an effect on progression free and overall survival in patients with EOC in first or second remission. The current study, CANVAS (CANcer VAccine Study) is evaluating Cvac treatment of EOC patients in first remission after surgery and standard chemotherapy, with at least three cycles of platinum and taxane therapy. Endpoints include progression free survival, overall survival, safety evaluation and quality of life scores. Methods: Patients are eligible if they have stage III or IV mucin-1 positive EOC and have had optimal cytoreductive (<1cm residual disease) surgery. Apheresis to obtain immature dendritic cells occurs prior to chemotherapy. Cvac is manufactured during chemotherapy. Patients remain eligible for the study if they have a complete response to standard chemotherapy after surgery. Cvac or placebo is dosed every four weeks for three doses, and every twelve weeks for three additional doses. 1000 patients will be randomized to Cvac or placebo in 22 countries, with 800 expected to receive vaccine or placebo. CT or MRI imaging determines progression, and is centrally read prior to inclusion and at each timepoint. Recruitment commenced January 2012. Over 100 centers are participating in the study globally, with majority in Europe. Enrollment is expected to take 18-24 months. An interim analysis is planned after 400 PFS events, and final analysis after 620 PFS events. Observation of 620 events would have approximately 90% power to detect a hazard ratio of 0.77 in PFS at a significance level of p=0.049 (approximately a 30% increase in median PFS in the Cvac group compared with the placebo group).
A phase III study of standard fractionation radiotherapy with concurrent high-dose cisplatin versus accelerated fractionation radiotherapy (RT) with panitumumab in patients with locally advanced stage III and IV squamous cell carcinoma of the head and neck (SCCHN) (NCIC Clinical Trials Group HN.6).
Authors: Waldron John N , Parulekar Wendy , O'Sullivan Brian , Chen Bingshu E , Montenegro Alexander , Nabid Abdenour , Winquist Eric , Wright Jim R. , Hay John , Ringash Jolie , Martino Rosemary , Johnson Ana , Liu Geoffrey , Breen Stephen , Gilbert Ralph William , Shenouda George , Siu Lillian L. 
Published: March 2020

TPS5600 Background: Standard treatment for locally advanced SCCHN, chemoradiotherapy (CRT), leads to significant acute and long-term morbidity. The demonstration that EGFR antibody (Ab) therapy improves outcome when added to standard RT (Bonner NEJM 2006) and that altered fractionation RT improves outcome compared to standard RT that is of similar magnitude as CRT (Bourhis Lancet 2006), led to the hypothesis that the combination of the two treatment strategies will improve efficacy compared to standard CRT with good tolerability. Methods: HN.6 is a Canadian phase III randomized study comparing standard RT 70Gy/35 over 7 weeks + cisplatin 100mg/m2 d 1, 22, 43 to accelerated RT 70Gy/35 over 6 weeks + panitumumab (anti EGFR Ab)) 9mg/kg 1 week prior to RT, d15, 36. Key eligibility criteria are: SCC of oral cavity, oropharynx, larynx or hypopharynx; TanyN+M0 or T3-4N0M0; adequate organ function and PS. Primary endpoint is progression free survival (PFS). Secondary endpoints include OS, local PFS, regional PFS, distant metastases, swallowing related QOL, functional swallowing outcomes, and economic evaluation (healthcare utilization, health utilities, indirect costs). Tissue and blood collection will allow biomarker evaluation including HPV status. Real time quality review of RT plans with plan data and radiology archiving will allow future analysis of RT parameters relative to toxicity and patterns of failure. Clinical epidemiological data will be prospectively collected and correlated with biomarkers and outcome. Planned sample size is 320 patients over 3.2 years with 3 more years of follow-up and target hazard ratio = 0.7 (absolute difference in control arm 2 year PFS of 12%, power 80%, 2-tail type 1 error 0.05). If superiority is not demonstrated, noninferiority will be tested. One interim analysis is planned. Conduct to Date: Study activation: Dec 2008 and completed accrual in Nov 2011. In Oct 2011, the DSMC recommended trial continuation. Supported by CCSRI grant 021039 and Amgen Inc. ClinicalTrials.gov: NCT00820248.