bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized phase III trial of regorafenib in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) progressing despite prior treatment with at least imatinib (IM) and sunitinib (SU): GRID trial.
Authors: Demetri George D. , Reichardt Peter , Kang Yoon-Koo , Blay Jean-Yves , Joensuu Heikki , Maki Robert G. , Rutkowski Piotr , Hohenberger Peter , Gelderblom Hans , Leahy Michael Gordon , von Mehren Margaret , Schoffski Patrick , Blackstein Martin E. , Le Cesne Axel , Badalamenti Giuseppe , Xu Jian-Ming , Nishida Toshirou , Laurent Dirk , Kuss Iris , Casali Paolo Giovanni ,   on behalf of GRID Investigators
Published: March 2020

LBA10008 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Monday, June 4, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Results of the X-PECT study: A phase III randomized double-blind placebo-controlled study of perifosine plus capecitabine (P-CAP) versus placebo plus capecitabine (CAP) in patients (pts) with refractory metastatic colorectal cancer (mCRC).
Authors: Bendell Johanna C. , Ervin Thomas J. , Senzer Neil N. , Richards Donald A. , Firdaus Irfan , Lockhart A. Craig , Cohn Allen Lee , Saleh Mansoor N. , Gardner Lesa R. , Sportelli Peter , Eng Cathy 
Published: March 2020

LBA3501 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
Interim analysis (IA) results of COU-AA-302, a randomized, phase III study of abiraterone acetate in chemotherapy-naive patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Ryan Charles J. , Smith Matthew Raymond , De Bono Johann Sebastian , Molina Arturo , Logothetis Christopher , De Souza Paul L. , Fizazi Karim , Mainwaring Paul N. , Piulats Rodriguez Jose Maria , Ng Siobhan , Carles Joan , Mulders Peter , Kheoh Thian San , Griffin Thomas W. , Small Eric Jay , Scher Howard I. , Rathkopf Dana E. ,   on behalf of the COU-AA-302 Investigators
Published: March 2020

LBA4518 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Saturday, June 2, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Axitinib versus sorafenib as second‑line therapy in Asian patients with metastatic renal cell carcinoma (mRCC): Results from a registrational study.
Authors: Qin Shukui , Bi Feng , Cheng Ying , Guo Jun , Ren Xiu Bao , Huang Yiran , Wang Jinwan , Ben Yong , Kim Sinil , Tang Jie , Ye Dingwei 
Published: March 2020

LBA4537 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Saturday, June 2, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Highly sensitive determination of PIK3CA exon 9 and 20 hotspot mutations in breast tumors.
Authors: Harle Alexandre , Lozano Nicolas , Nicolaizeau Cyrielle , Lion Maeva , Husson Marie , Rouyer Marie , Ramacci Carole , Genin Pascal , Merlin Jean-Louis 
Published: March 2020

TPS10634 Background: Hotspot mutations in exons 9 (E542K and E545K) and 20 (H1047L and H1047R) of PIK3CA gene encoding for the p110α catalytic subunit of Phosphatidylinositol 3-kinases (PI3K) are found in approximately 25% of breast carcinomas. PIK3CA mutations cause the overactivation of PI3K/AKT/mTOR pathway and lead to resistance to anti-HER2 targeted therapies in breast cancers, are involved in response to anti-mTOR agents and are proposed as molecular diagnosis marker for PI3K inhibitors. A highly sensitive method is required to detect PIK3CA mutations in paraffin-embedded tumor tissues. Methods: We developed a real-time PCR assay using allele-specific scorpion primers and amplification refractory mutation system (PCR-ARMS) to detect hotspot mutations in exons 9 (E542K and E545K) and 20 (H1047L and H1047R) of PIK3CA of PI3K. Results: PIK3CA mutations were analyzed in 102 paraffin embedded breast tumors (88 invasive ductal carcinomas and 14 lobular ductal carcinomas). All specimens were validated by pathologist examination and processed for DNA extraction and PCR. PIK3CA exon 9 and 20 mutations were found in 22.5% of the specimens, 39.1% in exon 9 (26.1% for E542K, 13.0% for E545K) and 60.9% in exon 20 (17.4% for H1047L and 43.5% for H1047R). These results were comparable to the literature data (χ²=0.327 ; p<0.05). PCR ARMS was found to be highly sensitive, able to detect 0.5 % mutated DNA. Conclusion: PCR ARMS assay is highly sensitive for PIK3CA exon 9 and exon 20 hotspot mutations analysis in breast carcinomas as molecular marker for anti-HER2 and PI3K inhibitors response prediction.
Phase III open-label, randomized, multicenter study of NKTR-102 versus treatment of physician's choice (TPC) in patients (pts) with locally recurrent or metastatic breast cancer (MBC) previously treated with an anthracycline, a taxane, and capecitabine (ATC).
Authors: Perez Edith A. , Awada Ahmad , O'Shaughnessy Joyce , Rugo Hope S. , Twelves Christopher , Cortes Javier ,   BEACON Study Group, Nektar Therapeutics, San Francisco, California
Published: March 2020

TPS1140^ Background: NKTR-102 is a topoisomerase I inhibitor-polymer conjugate that hydrolyzes to provide continuous exposure to SN-38. A phase 2 trial of single-agent NKTR-102 was conducted in pts with 3rd-line MBC; 2 schedules (q14d; q21d) investigated a dose of 145 mg/m2. ORR was 29% (including 3% CR) with the prior ATC subset demonstrating an ORR of 31%. Dosing q21d was better tolerated; in this arm, median PFS and OS equaled 5.3m and 13.1m, respectively. Trial Design: Pts will be randomized 1:1 to receive single-agent NKTR-102 or TPC in an open-label, randomized, multicenter phase 3 study in pts with advanced breast cancer. Key Entry Criteria: Adult females, with ECOG 0 or 1 with adequate liver, kidney and marrow function. All pts must have received prior therapy with ATC (these drugs can be administered in the neo/adjuvant or locally advanced/metastatic setting). Prior A is not mandated if contraindicated. Prior toxicities must have resolved to ≤ Grade 1 (except sensory neuropathy ≤ Grade 2; complete resolution of prior diarrhea). Pts with brain metastases may be eligible, if lesions are stable for prior 3 weeks without steroids. Methods: Primary efficacy endpoint is OS. Secondary endpoints include: ORR by RECIST v1.1, clinical benefit rate (ORR+SD > 6 months), PFS and QoL. NKTR-102 is given IV at 145 mg/m2 over 90-min every 21 days without premedications. Pts randomized to TPC receive 1 of the following: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel or nab-paclitaxel (the agent must be available at the treating institution). Pts are stratified by region, prior eribulin and receptor status (TNBC, Her2+ or Other). Target Accrual: ~840 pts will be required for sufficient events to occur in the planned follow-up time; OS will be compared using a two-sided log-rank test; 1 interim analysis will occur when 50% of the deaths are reported. PK sampling is performed in a subset of pts. CTCs (isolated by Apocell ApoStream technology) are serially assessed for potential predictive markers of response and toxicity. Enrollment is expected to remain open until late 2013.
Statin polyp prevention trial in patients with resected colon cancer: NSABP protocol P-5.
Authors: Boman Bruce M. , Bandos Hanna , Wickerham D. Lawrence , Petrelli Nicholas J. , O'Connell Michael J. , Wolmark Norman 
Published: March 2020

TPS1615 Background: HMG-CoA reductase inhibitors (statins) are effective lipid-lowering agents that are used for treating hyperlipidemia. Results from cell culture, animal experiments, and epidemiologic studies indicate that statins may be active chemopreventive agents against colorectal cancer (CRC). However, the clinical studies come largely from retrospective, observational studies originally designed to investigate lipid-lowering or cardiovascular endpoints rather than tumor endpoints. Methods: NSABP P-5 is a randomized, prospective placebo-controlled, double-blind study of rosuvastatin (10 mg per day x 5 years) or placebo for the prevention of adenomatous polyps of the colon or rectum, metachronous colorectal carcinoma, and colon cancer recurrence. Additional secondary endpoints include the size, number and features of the colorectal adenomas as well as health-related quality of life and self-reported symptoms. Selected Eligibility: (1) Patients who have undergone complete resection of AJCC Stage I or II colon cancer within 1 year before randomization. (2) Colonoscopy within 180 days before randomization. Selected Ineligibility: (1) Hyperlipidemia, (2) Familial Adenomatous Polyposis, (3) Lynch Syndrome. Sample Size:1,740 patients will be entered, and as of January 23, 2012, 163 (9.37%) have been randomized. The study is open at NSABP and CTSU sites in North America. Funded by NCI PHS grants U10-CA-37377 and U10-CA-6974, with additional funding from AstraZeneca Pharmaceuticals, LP.
O6-benzylguanine (BG) and temozolomide (TMZ) therapy of glioblastoma multiforme (GBM) with infusion of autologous lentiviral transduced P140KMGMT+ hematopoietic progenitors to protect hematopoiesis: A phase I study.
Authors: Sloan Andrew E. , Reese Jane , Rogers Lisa R. , Lo Simon S. , Nock Charles John , Lazarus Hillard M. , Machtay Mitchell , Fu PingFu , Fung Hua , Embree Heather , Dropulic Boro , Gerson Stanton ,   UO1 CA62502
Published: March 2020

TPS1616 Background: The administration of radiation therapy (RT) and concomitant and adjuvant temozolomide (TMZ) for the treatment of newly-diagnosed glioblastoma (GBM) is associated with modestly prolonged survival. However, the benefit of concurrent therapy is restricted to a subgroup of patients whose tumor exhibits methylation of the promoter for methylguanine-DNA-methyltransferase (MGMT). Promoter methylation silences the expression of DNA alkyltransferase (AGT), the product of the MGMT gene which functions to repair alkylated DNA. Unfortunately, the majority of GBMs have non-methylated MGMT promoters and do not appear to benefit from adding TMZ to radiotherapy. Two potential strategies for targeting MGMT-induced chemoprotection in gliomas include depletion of tumor MGMT, and dose escalation of TMZ accomplished by minimizing TMZ-induced bone marrow toxicity. In this study, we propose to combine the irreversible MGMT inhibitor O6-benzylguanine (BG) with infusion of autologous hematopoetic stem cells (HSCs) transduced with lentiviral P140K-MGMT, an MGMT mutant which is highly resistant to inactivation by BG, with the intent to reduce or prevent the myelosuppressive effects of TMZ. The primary objective is to assess the safety and feasibility of combining these two strategies in patients with newly-diagnosed GBM. Methods: This is a three cohort, Phase I study for patients with newly resected supratentorial GBM. There will be at least four evaluable patients per cohort. Cohort 1 will receive standard RT and concomitant TMZ prior to infusion of autologous lentiviral P140K-MGMT transduced HSCs, followed by adjuvant TMZ. Cohort 2 will receive an induction dose of TMZ+BG followed by infusion of autologous LV-P140K-MGMT HSCs prior to concomitant RT +TMZ and adjuvant TMZ. Cohort 3 will include intra-patient dose escalation of TMZ in patients who exhibit detectable levels of P140K-MGMT marked cells in vivo, using the design (i.e. cohort 1 or 2) proven to be safest and most effective. The study is open and has accrued the first patient.
A phase I study of BMS-936558 plus sunitinib or pazopanib in patients with metastatic renal cell carcinoma.
Authors: Hammers Hans J. , Rini Brian I. , Hudes Gary R. , Ernstoff Marc S. , Kollmannsberger Christian K. , Shen Yun , Waxman Ian , Dhar Arindam 
Published: March 2020

TPS2614 Background: Standard treatments for metastatic renal cell carcinoma (mRCC) block the vascular endothelial growth factor pathway (eg, sunitinib, pazopanib) or mammalian target of rapamycin pathway (e.g., temsirolimus, everolimus). However, most patients (pts) develop resistance and complete responses are rare. Upregulation of programmed death-1 (PD-1) in tumor infiltrating lymphoctyes, and its ligand PD-L1 in tumors, is associated with more aggressive disease and poor prognosis. Blocking the PD-1/PD-L1 interaction is a novel immunotherapeutic approach for mRCC. In preliminary results of a phase I trial, the anti-PD-1 monoclonal antibody BMS-936558 had antitumor activity in pts with advanced tumors, including objective responses (ORs) in 6 of 18 pts with mRCC. Here we describe a phase I study planned to evaluate the safety, tolerability, and maximum tolerated dose (MTD) of BMS-936558, when combined with sunitinib or pazopanib in pts with mRCC. Methods: This open-label study will have two parallel treatment arms (BMS-936558 plus sunitinib and BMS-936558 plus pazopanib) conducted in two parts (dose escalation and dose expansion). Pts must have received ≥1 prior systemic therapy to be eligible for dose escalation. Only treatment-naïve pts will be eligible for dose expansion. Up to 36 pts (18 per arm) will be treated in the dose-escalation phase. After determining the MTD of BMS-936558, treatment-naïve pts will be enrolled to expansion cohorts allowing 24 pts to be treated at the MTD of each arm. Each treatment cycle will be 6 weeks, with BMS-936558 dosed on Days 1 and 22 and sunitinib or pazopanib given according to product label. Adverse events will be graded according to NCI CTCAE v4.0. Disease will be assessed every 6 weeks for the first four assessments and then every 12 weeks until disease progression. Pts will be treated until unacceptable toxicity, disease progression, or withdrawal of consent. The safety profile in pts treated at the MTD will be used to determine the recommended phase II study dose of BMS-936558 in each combination arm. Secondary objectives will include OR rate and duration of response based on RECIST 1.1. Exploratory analyses will investigate predictive biomarkers of BMS-936558.
First-in-human phase I trial of NHS-IL12 in advanced solid tumors.
Authors: Kim Joseph W. , Heery Christopher Ryan , Bilusic Marijo , Singh Nishith K. , Madan Ravi A. , Sabzevari Helen , Schlom Jeffrey , Gulley James L. 
Published: March 2020

TPS2617 Background: NHS-IL12 is an antibody-cytokine conjugate consisting of two heterodimers of interleukin (IL)-12, fused to a human monoclonal antibody specific for DNA-histone H1 complex exposed in tumor necrosis. IL12 is a proinflammatory cytokine, produced by activated phagocytes and dendritic cells, that plays a critical role in regulating the transition from innate to adaptive immunity. Early clinical trials of IL12 reported clinical responses in metastatic renal cell carcinoma, Kaposi sarcoma (50–71% response rate), T-cell lymphoma (56%), and non-Hodgkin’s lymphoma (21%). However, systemic toxicity limited further clinical development. NHS-IL12 is designed to reduce toxicity associated with systemic administration of IL12 by selectively targeting delivery to necrotic areas of tumors. A fluorescence imaging study of NHS-murine (mu)-IL12 in mice with syngeneic lung carcinoma demonstrated effective targeting by NHS-muIL12. Immunohistochemistry studies further confirmed effective targeting of tumors by NHS-muIL12. In another study in canines with spontaneously occurring solid tumors, 2 of 11 subjects achieved a partial response with a single dose. Methods: This is a phase I dose-escalation study designed to determine the maximum tolerated dose of NHS-IL12 and to define the biologically optimal dose and schedule based on immunologic (pharmacodynamic) analysis of cytokines such as interferon-g, and IL-10, at multiple times points from 4 hours up to 2 weeks following the administration of NHS-IL12. Eligible patients (pts) include those with evaluable or measurable solid tumors who have progressive disease on at least one prior line of therapy. Pts with a condition associated with significant necrosis of non-tumor bearing tissue, (e.g., ulcerative colitis), are excluded. Modified immune-related response criteria are used to assess response, the major features of these criteria being (a) imaging confirmation of both progression and response at least 4 weeks after initial imaging, and (b) no consideration of new lesions unless the total measurable tumor burden meets the criteria for progressive disease. This trial opened to accrual in Nov. 2011 and may enroll up to 78 pts.
Safety, pharmacokinetics, and antitumor activity of MEDI3617, a selective angiopoietin inhibitor, in adult patients with advanced solid tumors.
Authors: Natale Ronald B. , Rizvi Naiyer A. , Infante Jeffrey R. , Joseph Lindsay J. , Viner Jaye , McDevitt Jennifer T. , Ji Fei , Shin Soyoung , Liang Meina , Burris Howard A. 
Published: March 2020

TPS2621 Background: MEDI3617 is an investigational monoclonal antibody that inhibits angiogenesis by preventing the interaction of angiopoietin-1 and angiopoietin-2 (Ang2) ligands with the Tie2 receptor. Methods: This is an ongoing phase 1 dose-escalation and dose-expansion study in patients with advanced solid tumors, Karnofsky performance status ≥70, and adequate organ function. Patients were treated with escalating IV doses of MEDI3617 on day 1 of each 21 day cycle in cohorts of 3-6 patients. The objectives are to evaluate the safety profile and determine the maximum tolerated dose, dose-limiting toxicities (DLT), pharmacokinetics, pharmacodynamics, and clinical activity of MEDI3617. Results: Preliminary data are presented for 21 patients (14M/7F), median age 65 yrs, evaluable for DLT. One DLT occurred: grade 4 neutropenia lasting more than 7 days. The most frequently reported drug-related adverse events (% of patients) were fatigue (24%), diarrhea (19%), nausea (19%), dysgeusia (14%), and headache (14%), all of which were ≤ grade 2. All monotherapy dose levels have completely enrolled patients without exceeding the maximum tolerated dose. The exposure of MEDI3617 after the first dose showed a more than dose-proportional increase. Suppression of free Ang2 was dose-dependent. Maximum accumulation of total Ang2 was observed at the lowest administered dose. No anti-MEDI3617 neutralizing antibodies were detected. Of the 21 patients, 4 continue on treatment (maximum of 6+ months in a patient with carcinoid tumor of the jejunum) as of the data cut-off date. Of the 17 patients for whom response data are available, 5 had stabilization of disease of 12 weeks or greater. Conclusions: Preliminary safety and activity signals warrant continued evaluation of MEDI3617. This study was funded by MedImmune, LLC.
A dose escalation, single arm, phase Ib/II combination study of BEZ235 with everolimus to determine the safety, pharmacodynamics, and pharmacokinetics in subjects with advanced solid malignancies including glioblastoma multiforme.
Authors: Salkeni Mohamad Adham , Beg Muhammad Shaalan , Olowokure Olugbenga Olanrele , Fathallah Hassana , Thomas Hala , Mercer Carol A , Charif Mahmoud , Chaudhary Rekha T. , Abdel Karim Nagla , Warnick Ronald , McPherson Christopher , Moorthy Ganesh , Desai Pankaj B , Kozma Sara , Thomas George , Rixe Olivier 
Published: March 2020

TPS3116 Background: Downregulation of a number of signaling pathways, including the mammalian target of rapamycin (mTOR) pathway, has been demonstrated to be efficacious in a large range of solid tumors such as breast, colon, endometrial, glial and hepatocellular carcinoma (HCC). However, we find that rapamycins lead to suppression of a negative feedback loop from S6 Kinase 1 (S6K1) to Protein Kinase B (PKB), leading to hyperactivation of PKB. In pre-clinical studies using a mouse model of carcinogen-induced HCC, we have demonstrated that combining BEZ235 (a potent and highly selective reversible ATP site competitive inhibitor of PI3K and mTOR) with everolimus (an allosteric inhibitor of mTOR) synergizes to inhibit tumor growth. BEZ235, an orally administered agent, has demonstrated preliminary antitumor activity in a first-in-human phase I study. The current study will evaluate this combination in patients with a variety of solid malignancies that includes glioblastoma multiforme (GBM). Methods: This study is divided into a phase 1b portion designed to determine safety of increasing doses of the combination, with extensive pharmacokinetics, pharmacodynamics and pharmacogenomics analysis; and a phase 2 portion that includes both solid tumors and GBM based on predominance of the mTOR and PI3K deregulation in these tumors, to determine preliminary anti-tumor activity and the recommended dose for phase 2 studies. We will also integrate biomarker assessment for gene expression products of the mTOR downstream pathway such as eukaryotic initiation factor 4E binding protein (4EBP1) and S6 kinase (S6K). The phase 1b portion has started accruing.
A randomized, double-blind, phase (Ph) III study of the irinotecan-based chemotherapy FOLFIRI plus ramucirumab (RAM) or placebo (PL) in patients (pts) with metastatic colorectal carcinoma (mCRC) progressive during or following first-line therapy with bevacizumab (BEV), oxaliplatin (OXALI), and a fluoropyrimidine (FP) (RAISE) (NCT01183780).
Authors: Grothey Axel , Tabernero Josep , Rougier Philippe , Ballal Shaila , Crane Heidi , Rutstein Mark D. 
Published: March 2020

TPS3634 Background: Vascular endothelial growth factor (VEGF) and the VEGF receptor-2 (VEGFR-2) regulate angiogenesis and are overexpressed in CRC. RAM is a fully human IgG1 monoclonal antibody that inhibits binding of VEGF ligands to VEGFR-2 and inhibits VEGFR-2 activation and signaling. In a preclinical study, antiangiogenic and antitumor effects were observed when DC101, an antibody that targets murine VEGFR-2, was administered to mice bearing human colon cancer xenografts. Antitumor activity for RAM has been demonstrated in a Ph I study in pts with solid tumors over a wide range of RAM dose levels and in a Ph II study with RAM + mFOLFOX-6 as 1st-line therapy in pts with mCRC. Methods: This ongoing, randomized, double-blind, placebo-controlled Ph III study includes mCRC pts with measurable or nonmeasurable disease and ECOG performance status of 0-1 who have experienced disease progression during or within 6 months following 1st-line therapy with BEV, OXALI, and any FP. Randomization is stratified by geographic region, KRAS status, and time to progression after initiation of 1st-line therapy. Pts are randomized 1:1 to either RAM 8 mg/kg or PL every 14 days. Pts in both arms receive FOLFIRI (irinotecan: 180 mg/m2, folinic acid: 400 mg/m2, 5-fluorouracil: 400 mg/m2 bolus followed by 2400 mg/m2 continuous infusion over 46-48 hours). The primary endpoint is overall survival (OS). The sample-size estimate assumes 85% power to detect at least a 2.5-month median OS difference (HR = 0.8) between treatment arms with a 1-sided alpha of 0.025. Secondary endpoints include progression-free survival, tumor response, safety, pharmacokinetics, immunogenicity, and correlations between biomarkers and clinical outcome. CRC tissue and blood collection is mandatory for biomarker analyses. As of 05 January 2012, 238 of 1050 planned pts have been enrolled from 100 sites in North America, South America, Europe, Asia, and Australia.