bluuebunny/crossref_metadata_2025_split huggingface dataset:
PaFLO: Pazopanib with 5-fluorouracil, leucovorin, and oxaliplatin (FLO) as first-line treatment in advanced gastric cancer: A randomized phase II study of the Arbeitsgemeinschaft internistische Onkologie (AIO).
Authors: Breithaupt Kirstin , Bichev Dmitry , Lorenz Mario , Bohnen Daniela , Dogan Yasemin , Schlattmann Peter , Al-Batran Salah-Eddin , Moehler Markus Hermann , Thuss-Patience Peter C. 
Published: March 2020

TPS4138 Background: VEGF inhibition in gastric cancer shows promising improvement of remission rate and progression-free survival (Ohtsu et al., JCO 2011). Pazopanib is an orally available tyrosine kinase inhibitor (TKI) selectively inhibiting VEGFR-1, -2, -3, c-kit and PDGFR. It is approved for treating renal cell cancer. A phase-I trial showed good tolerability of pazopanib with full-dose FOLFOX in solid tumors (Brady et al., ASCO, 2009). FLO is a widely used combination for advanced gastric cancer recommended in national guidelines. Methods: 75 Patients with HER-2-negative locally advanced or metastatic adenocarcinoma of the stomach or the gastro-esophageal junction will be randomized in a 2:1 ratio to A: FLO (F 2600mg/m2 as 24h infusion, L 200mg/m2, O 85 mg/m2) d1 + pazopanib (800mg) d1-14 and B: FLO; repeated for 12 2-week cycles, followed by a maintenance therapy with pazopanib alone in A and an observation period in B until disease progression. Primary endpoint is progression-free survival rate (PFSR) at 6 months, secondary endpoints are PFSR at 9 and 12 months, median PFS, response rate, duration of response, toxicity, tolerability and overall survival. Additionally, we evaluate the predictive and prognostic relevance of PIGF, VEGF, and the respective soluble receptors sVEGFR1 and sVEGFR2 as biomarkers for clinicopathological parameters, clinical response to treatment and tumor volume change. Based on a phase-III trial demonstrating a 6-month PFSR of 44% with FLO (Al-Batran et al., 2008), we estimate a 6-month PFSR of 55% in the experimental group. Given an alpha error of 0.1 and a beta error of 0.2 in a Simon 2-stage minimax design, in the first stage ≥12 of 30 patients need to be progression free at 6 months to continue and after the second stage ≥25 of 50 patients should be progression free at 6 months to justify further evaluation. Randomization is performed to estimate selection bias according to pazopanib-specific exclusion criteria for comparison with historical data. Study protocol received ethics committee approval in November 2011 and is currently recruiting patients in 15 AIO centers.
Postoperation chemotherapy with S1 and docetaxel in curatively resected gastric cancer of stage III (POST trial).
Authors: Jung Minkyu , Kang Seok Yun , Kim Bong-Seog , Kim Ki Hyang , Lee Kyung Hee , Lee Moon Hee , Shin Dong Bok , Zang Dae Young , Noh Sung Hoon , Chung Hyun Cheol , Rha Sun Young 
Published: March 2020

TPS4142 Background: Complete surgical resections remains the only chance for cure in patients with gastric cancer, but approximately from 40% to 80% of patients still have recurrences and most patients ultimately die from their disease. The recent adjuvant trials in gastric cancer showed significantly improved survival in patients with adjuvant chemotherapy than those with surgery alone. However, further studies need for the effect of adjuvant chemotherapy following D2 dissected gastric cancer patients, especially in advanced gastric cancer. S-1 is an oral anticancer drug, a prodrug of fluorouracil, very effective in gastric cancer. Docetaxel is the first drug that showed survival benefits when added to the two drugs in advanced gastric cancer patients. And docetaxel is also synergistic anti-cancer effect with S-1 in advanced gastric cancer. Base on this background, the aim of this study is to detect a significant increase in 3 –year disease free survival (DFS) of adjuvant chemotherapy with docetaxel and S-1(DS) relative to those with S-1 and cisplatin (SP) in patients with stage III gastric cancer Methods: This study is an open-label, phase 3, randomized controlled trial, multicenter in South Korea. Patients with stage III (AJCC 7th edition) gastric cancer who had had curative D2 gastrectomy is randomly assigned to receive adjuvant chemotherapy of eight 3-week cycles of intravenous docetaxel (35 mg/m2 on day 1 and 8 of each cycle) plus oral S-1 (35 mg/m2 twice daily on days 1 to 14 of each cycle) for 6 months (DS) or chemotherapy of eight 3-week cycles of oral S1 plus intravenous cisplatin (60 mg/m2). After satisfying the screening criteria, patients have been randomized to the SD or SP arm in a 1:1 ratio. The randomization is stratified by institution and stage of disease (IIIA vs. IIIB vs. IIIC). The each stratum has been randomized by using the method of randomly permuted block. The primary endpoint is 3 year DFS, will analyze by intention to treat. A total of 290 patients will be enrolled, 67 patients have been treated to day, with continuing accrual. The trial is registered at ClinicalTrials.gov (NCT01283217).
Phase II trial of gemcitabine and cisplatin plus ipilimumab as first-line treatment for metastatic urothelial carcinoma.
Authors: Gartrell Benjamin Adam , Hahn Noah M. , Hutson Thomas E. , Sonpavde Guru , Hauke Ralph J. , Starodub Alexander , Small Alexander C. , Tsao Che-Kai , Galsky Matt D. 
Published: March 2020

TPS4676 Background: While metastatic urothelial carcinoma is a chemosensitive neoplasm, current therapeutic approaches are inadequate. Preclinical and clinical data suggests that bladder cancer is immunogenic. For example, CD8+ tumor infiltrating lymphocytes correlate with survival in patients with muscle-invasive disease (Sharma, PNAS, 2007). However, immunotherapeutic approaches have been rarely investigated for advanced urothelial cancer. CTLA4 blockade with ipilimumab is a novel approach to immunotherapy that interrupts T-cell pathways responsible for immune down-regulation or tolerance. In a proof of concept study, ipilimumab was administered to 12 patients with muscle-invasive disease preoperatively (Carthon, Clin Can Res, 2010). Treatment resulted in perivascular infiltration of cells positive for CD3, CD8, CD4, and granzyme and intriguing evidence of antitumor activity. In the current trial, we will explore a “phased” schedule of chemotherapy and ipilimumab with the goal of “autovaccinating” patients to tumor antigen with chemotherapy prior to introduction of immune checkpoint blockade. Methods: We have initiated a phase II clinical trial of gemcitabine (G), cisplatin (C), plus ipilimumab in chemonaive patients with unresectable and/or metastatic urothelial cancer within the Hoosier Oncology Group network. During cycles 1 and 2, G (1000 mg/m2 D day 1 + 8) and C (70 mg/m2 D 1) will be administered every 21 days without ipilimumab. During cycles 3-6, GC plus ipilimumab (10 mg/kg day 1) will be administered every 21 days. Patients without evidence of disease progression after completion cycle 6 will continue single-agent ipilimumab “maintenance” every 3 months. The primary objective is to determine the 1-year overall survival. The trial will enroll 36 patients and is powered to detect an improvement in 1-year survival from 60% to 80%. Secondary objectives include progression-free survival, disease control rate, safety, and immunologic outcomes. Correlative studies will include serial measurements of the global composition of immune cells in the blood by polychromatic flow cytometry, whole blood transcriptional profiling, and tumor-antigen specific CD8+ T cells assays.
Phase I/II study of high-dose interleukin 2, aldesleukin, in combination with the histone deacetylase inhibitor entinostat in patients with metastatic renal cell carcinoma.
Authors: Pili Roberto , Shen Li , George Saby , Hammers Hans , Sandecki Anita , Collins Connie , Espinoza-Delgado Igor , Carducci Michael Anthony 
Published: March 2020

TPS4687 Background: Immunosuppressive factors such as regulatory T cells (Tregs) limit the efficacy of immunotherapies. Histone deacetylase (HDAC) inhibitors have been shown to have anti-tumor activity in different malignancies and to induce immuno-modulatory effects. We have previously reported that a class I specific HDAC inhibitor, entinostat, has synergistic anti-tumor effect in combination with high dose interleukin-2 (IL-2) in a renal cell carcinoma model (Kato Y et al Clinical Cancer Res 2007). Our group has also recently showed that low dose entinostat induces STAT3 acetylation, down-regulates Foxp3 expression in Tregs, and blocks Tregs suppressive function without affecting T effector cells (Shen Li et al PLoSONE 2012). Methods: Based on these preclinical evidences we have initiated a Phase I/II clinical study with entinostat and high dose IL-2 in patients with metastatic renal cell carcinoma. The primary objective of the study is to evaluate the safety, tolerability and efficacy of this combination strategy. The main eligibility criteria are clear cell histology, no prior treatments and being fit to receive high dose IL-2. The Phase I portion consists of two dose levels of entinostat (3 and 5 mg) and a fixed standard dose of IL-2 (600,000 units/Kg every 8 hrs.) according to a 3+3 design. The sample size of 36 patients in the Phase II portion is powered to detect an increase in objective response rate from 20% to 40% as compared to historical data with high dose IL-2 alone. Correlative studies include assessment of CD4+, CD8+, CD4+/Foxp3, NK cells in tumor and blood samples by immunohistochemistry and FACS analysis, and tumor metabolism by FDG PET. We are also exploring the relationship between entinostat exposure with pharmacodynamic endpoints. To date dose level one has been completed without DLT. Enrollment to dose level two has begun in the Fall 2011. The results from this study may confirm the role of entinostat in enhancing the effect of IL-2 and may be translated into other combination strategies involving immunotherapies. The clinical trial and correlative studies are supported by the National Cancer Institute- R21CA137649.
Phase II study of dovitinib in first-line metastatic or nonresectable primary adrenocortical carcinoma (ACC): SOGUG study 2011-03.
Authors: Jimenez Paula , Guix Marta , Lainez Milagro Nuria , Leon Mateos Luis , Mendez Vidal Maria Jose , Climent Duran Miguel Angel , Garcia-Donas Jesus ,   Spanish Oncology Genitourinary Oncology Group (SOGUG)
Published: March 2020

TPS4688 Background: Dovitinib is a novel targeted therapy, that has proven to inhibit, among other tyrosin kinases, the fibroblast growth factor receptor (FGFR). Since this pathway has been proposed to play a major role in ACC, we aim to test the clinical efficacy of dovitinib in this tumor. Methods: An open label phase II trial has been designed in patients with advanced non-resectable ACC. The objective will be to obtain at least a 15% response rate according to RECIST criteria. Taking as a basis the two-stage Gehan model, 15 patients would need to be included in the first stage to demonstrate a treatment efficacy of at least 15%. Sample size calculation was done based on the following parameters, probability of Type I error α = 0.05, power of the test (1 - β) = 0.8. Main inclusion criteria are advanced non-resectable disease and no prior therapy (other than mitotane). Dovitinib scheduled dose matches currently employed standard in the drug development (500mg daily for 5 days then 2 days off) for 6 months. If clinical benefit is obtained longer treatment will be allowed for particular patients. Since this is an extremely unfrequent disease 7 institutions, members of the SOGUG (Spanish Oncology Genitourinary Group), will participate. The active support of a big collaborative group will guarantee candidate patients to be refereed to such institutions. Starting January 26th 2012 recruitment is scheduled to last around 12 months. A translational research, including whole exome analysis, will be performed in order to improve our scarce knowledge of ACC.
CA184-095: A randomized, double-blind, phase III trial to compare the efficacy of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients (pts) with metastatic chemotherapy-naive castration-resistant prostate cancer (CRPC).
Authors: Beer Tomasz M. , Logothetis Christopher , Sharma Padmanee , Bossi Alberto , McHenry Brent , Fairchild Justin P. , Gagnier Paul , Chin Kevin M. , Cuillerot Jean-Marie , Fizazi Karim , Gerritsen Winald R. 
Published: March 2020

TPS4691 Background: Ipilimumab (Ipi), a fully human monoclonal antibody which blocks CTLA-4, augments antitumor immune responses. Ipi has demonstrated overall survival (OS) benefit in two Phase 3 trials for advanced melanoma, with side effects that were managed using product-specific treatment guidelines. In addition, in Phase 1/2 trials in metastatic CRPC, Ipi has shown clinical activity (as measured by prostate-specific antigen [PSA] declines and RECIST response) with no unexpected toxicities. While docetaxel is standard therapy for metastatic CRPC, its use may be delayed until pts develop symptoms. As such, this global (~150 sites in 25 countries) Phase 3 study (ClinicalTrials.gov identifier: NCT01057810) is evaluating Ipi vs placebo in chemotherapy-naïve pts with asymptomatic or minimally symptomatic CRPC without visceral metastases. Methods: The primary endpoint is OS; secondary endpoints include progression-free survival, time to pain progression, and time to non-hormonal systemic therapy. The study is designed to detect a 9.3 month difference (HR=0.7) in OS with 90% power and 0.05 two-sided significance. Pts are randomized at a 2:1 ratio to receive Ipi 10 mg/kg every 3 weeks for up to 4 doses or placebo, respectively, as induction therapy. Eligible pts will continue to receive maintenance therapy of blinded study drug every 12 weeks until treatment stopping criteria are met, withdrawal of consent, or study closure. The accrual goal is 600 pts randomized. [Table: see text] [Table: see text]
First-line use of cabazitaxel in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC): A three-arm study in comparison with docetaxel.
Authors: Oudard Stephane , Sengelov Lisa , Mainwaring Paul N. , Thiery- Vuillemin Antoine , Theodore Christine , Kulikov Evgeny , Yachnin Jeffrey , Kocak Ivo , Kataja Vesa V , Luukkaa Marjaana , Nosov Aleander , Hjelm-Eriksson Marie , Bubis Jeffrey , Shen Liji , Risse Marie-Laure , Sartor A. Oliver 
Published: March 2020

TPS4696^ Background: Docetaxel (D) in combination with prednisone (P) as first-line (1L) chemotherapy in patients (pts) with mCRPC is the current standard of care. However, treatment is not curative and D-resistant disease typically develops. Cabazitaxel (Cbz) is a novel taxane active in D-sensitive and -resistant tumor models. Clinical activity of Cbz plus P (CbzP) was demonstrated in the Phase III TROPIC study in mCRPC pts previously treated with a D-containing regimen; CbzP showed a significant overall survival (OS) benefit vs mitoxantrone plus prednisone (median OS 15.1 vs 12.7 months; HR 0.70; P < 0.0001). Therefore, it is of interest to determine if CbzP provides an OS advantage vs DP in 1L mCRPC pts. Methods: The phase III FIRSTANA study (NCT01308567) is a randomized, open-label, multinational trial in 1L mCRPC pts, designed to compare the efficacy of Cbz 25 mg/m² IV Q3W (Arm A) and Cbz 20 mg/m² IV Q3W (Arm B) vs D 75 mg/m2 IV Q3W (Arm C). P 10 mg PO QD is to be given concomitantly. Pts are stratified by ECOG PS (0–1 vs 2), measurable disease (yes/no) and region (depending on availability of Cbz as 2L). Pts with ECOG PS ≤ 2, histologically/cytologically confirmed metastatic prostate adenocarcinoma, with no prior chemotherapy and with disease progression following medical or surgical castration are eligible. The primary endpoint is OS. Secondary endpoints include progression-free survival (PFS) (PCWG2 criteria), radiologic PFS, tumor response in measurable disease (RECIST 1.1), PSA response and PSA PFS, pain response and pain PFS, time to occurrence of any skeletal-related events, safety profile and health-related quality of life. Cbz pharmacokinetics and pharmacogenomics will be assessed in pt subgroups. Pts will be treated until progression, unacceptable toxicity or pt request. Planned enrollment is 1,170 pts; study size was calculated to achieve 90% power for OS. Study start was in May 2011; at January 2012, 219 pts were enrolled. The first DMC meeting recommended continuing the study without change.
A phase II study of the androgen signaling inhibitor ARN-509 in patients with castration-resistant prostate cancer (CRPC).
Authors: Rathkopf Dana E. , Shore Neal , Antonarakis Emmanuel S. , Berry William R. , Alumkal Joshi J. , Tutrone Ronald , Saleh Mansoor N. , Redfern Charles H. , Hauke Ralph J. , Liu Glenn , Steinbrecher Jill Elise , Danila Daniel Costin , Curley Tracy , Arauz Gabrielle , Rix Peter J. , Maneval Edna Chow , Chen Isan , Scher Howard I. 
Published: March 2020

TPS4697 Background: ARN-509 is a novel small molecule androgen signaling inhibitor that impairs AR nuclear translocation and binding to DNA, inhibiting tumor growth and promoting apoptosis, with no partial agonist activity. Preclinical data suggests that the maximal therapeutic index of ARN-509 can be achieved at low steady state plasma levels with minimal toxicity (Clegg et al, 2012). Enrollment in the Phase 1 dose escalation study of ARN-509 in patients with progressive CRPC with and without prior chemotherapy was completed in January 2012. The recommended Phase 2 dose of 240 mg was determined based on safety, PSA kinetics, and pharmacokinetic and pharmacodynamic analysis (Rathkopf et al, GU ASCO, 2012). Methods: The primary objective of this Phase 2 study is to determine the PSA response at 12 weeks according to Prostate Cancer Working Group 2 (PCWG2) Criteria (Scher et al, 2008). Three expansion cohorts will enroll a total of 80-90 patients for treatment with 240 mg continuous oral ARN-509 daily. These cohorts include: 1) non-metastatic treatment-naïve CRPC (50 patients); 2) chemotherapy-naïve metastatic (m) CRPC (20 patients); and 3) chemotherapy-naïve, post abiraterone mCRPC (10-20 patients). The effect of food on the PK of ARN-509 and the effect of ARN-509 on ventricular repolarization will also be evaluated. Phase 2 enrollment is ongoing. DOD/PCF PCCTC trial sponsored by Aragon Pharmaceuticals. NCT01171898.
ACRIN 6695 perfusion CT as prognostic imaging biomarker in ovarian cancer.
Authors: Ng Chaan S. , Lee Ting Yim , Coleman Robert L. , Zhang Zheng , Dunning Bernadine , L'Heureux Darryl , Mannel Robert S. , Lee Susanna 
Published: March 2020

TPS5114 Background: Tumor size and the cell surface glycoprotein CA125 levels have been traditional biomarkers for ovarian carcinoma, but remain suboptimal for assessing patients receiving chemotherapy. Current morphological criteria do not adequately evaluate lesion necrosis from anti-angiogenic therapy when no tumor volume change is measured. The evaluation of functional biomarkers rather than tumor volume may better distinguish responders from non-responders early in treatment with anti-angiogenic therapy. Perfusion CT can evaluate changes in tumor vascularity including blood flow (BF), blood volume (BV), mean transit time (MTT) and capillary permeability surface product (PS) before and after anti-angiogenic therapy with/out decrease in tumor volume. Objectives: The aims of the study are to evaluate the relationship between changes in tumor perfusion parameters and clinical outcomes of progression free survival, overall survival, and standard RECIST anatomic response criteria. A test-retest perfusion CT scan will also be performed to evaluate reproducibility of perfusion parameters in a subset of participants. Methods: In this collaborative trial, participants will be co-enrolled in the GOG-262 treatment trial. Participants will receive doublet chemotherapy of paclitaxel and carboplatin, followed by anti-angiogenic monoclonal therapy at cycle two. Perfusion CT will be performed at three time points: at baseline prior to therapy (T0), between days 18 and 21 of cycle one chemotherapy (T1), and at 8-10 days (T2) in anti-angiogenic monoclonal therapy. Participants with primary epithelial ovarian, peritoneal or fallopian tube cancer with optimally or suboptimally debulked FIGO Stage II, III or IV disease are eligible for the trial. Lesion eligibility will be evaluated by size and attenuation criteria. Accrual: ACRIN 6695 is activated at 12 GOG sites; 4/78 participants have accrued Discussion: Perfusion CT has been readily incorporated into the pre-existing clinical CT protocols and during scheduled RECIST scans. These perfusion CT functional maps of BF, BV, MTT and PS have been generated using vendor provided software without issue. Contact: Please contact Chaan Ng, MD cng@mdanderson.org for additional information.
LUX-breast 2: Phase II, open-label study of oral afatinib in HER2-overexpressing metastatic breast cancer (MBC) patients (pts) who progressed on prior trastuzumab (T) and/or lapatanib (L).
Authors: Hickish Tamas , Tseng Ling-Ming , Mehta Ajay O. , Tsang Janice , Kovalenko Nadezhda , Udovitsa Dmitry , Pelling Katy , Uttenreuther-Fischer Martina Maria , Huang Chiun-Sheng ,   LUX-Breast 2 Study Group
Published: March 2020

TPS651 Background: Management of HER2-overexpressing MBC has improved over the past decade. However, pts still develop resistance to currently available HER2-targeted therapies and novel effective treatments are increasingly required as dual targeted combinations are given in early treatment lines already. Current therapies focus on targeting HER2 and do not inhibit all relevant ErbB Family dimers. Afatinib is an oral, irreversible ErbB Family Blocker that inhibits signaling through activated EGFR (ErbB1), HER2 (ErbB2) and ErbB4 receptors and transphosphorylation of ErbB3. Preclinical studies have demonstrated efficacy in T-sensitive and T-resistant human BC xenograft models dependent on ErbB signaling. Efficacy of afatinib in a T-resistant SUM 190 xenograft model has been shown to be increased by addition of IV vinorelbine (V). Afatinib monotherapy has shown promising clinical benefit in 46% of HER2-overexpressing MBC pts who progressed on prior T, with 10% of pts achieving PR. Methods: This open-label Phase II trial (NCT01271725) investigates efficacy and safety of afatinib alone (40 mg/d) followed by afatinib ‘beyond progression’ plus chemotherapy in 120 pts with HER2-overexpressing MBC, who progressed on prior neoadjuvant and/or adjuvant T and/or L. Pts who progress on afatinib monotherapy receive afatinib plus either weekly paclitaxel (P) 80 mg/m2 or V 25 mg/m2. Eligible pts have confirmed HER2-overexpressing BC, stage IV disease measurable by RECIST 1.1, progressed on T and/or L therapy in either neoadjuvant and/or adjuvant setting, are eligible for retreatment with P or V and should not have been pretreated with P (≤12 months) or V, respectively. Exclusion criteria: inadequate cardiac, renal, hepatic and hematological function, pre-existing gastrointestinal dysfunction, rapidly progressing visceral disease, ILD and active brain metastases. The primary endpoint is objective response (OR) and secondary endpoints include best overall response, duration of OR and PFS; safety will be assessed separately for afatinib mono- and combination therapy. Patient enrollment began in May 2011 in ~35 sites and 5 countries.