bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Pacific trial: A randomized phase II study of OGX-427 in men with metastatic castration-resistant prostate cancer (mCRPC) and PSA progression while receiving abiraterone acetate (AA).
Authors: Chi Kim N. , Sweeney Christopher , Jacobs Cindy , Stewart Patricia S. , Hahn Noah M. 
Published: March 2020

TPS5101 Background: Heat Shock Protein 27 (Hsp27) is a multi-functional chaperone protein that regulates cell signaling and survival pathways implicated in cancer progression and over-expressed in many cancers including prostate, bladder, lung, and breast. In prostate cancer models, Hsp27 complexes with androgen receptor (AR) and enhances transactivation of AR-regulated genes. OGX-427 is a second-generation antisense oligonucleotide designed to inhibit Hsp27 expression with in vitro and in vivo efficacy that increases apoptosis, inhibits tumor growth, sensitizes cells to chemotherapy and inhibits AR activity (Cancer Res 2007;67(21):10455). A phase 2 study of OGX-427 in patients with mCRPC reported preliminary activity with 50% of patients having a ≥50% PSA decline during treatment (J Clin Oncol 30, 2012 (suppl; abstr 4514)). The purpose of this study was to evaluate the clinical activity of OGX-427 in patients with mCRPC progressing on AA. Methods: In this randomized, phase 2 study, 74 evaluable patients with mCRPC who are currently receiving AA and have PSA progression despite a prior response are randomized 1:1 to receive either OGX-427 (600 mg IV x 3 loading doses in week 1 followed by 1000 mg IV weekly) with AA or continuing AA alone. Additional eligibility criteria include: ECOG performance status ≤1, no evidence of radiographic progression, adequate liver/kidney/bone marrow function, and ≤1 prior chemotherapy for CRPC. Protocol therapy is continued until disease progression, unacceptable toxicity, or patient withdrawal. Eligible control arm patients may cross over to receive OGX-427 following disease progression. The primary objective of the study is to evaluate the proportion of patients progression-free at Day 60 post randomization. Secondary objectives include comparisons between arms of PSA and disease response, progression free survival, time to disease progression, serial serum levels of Hsp27, and circulating tumor cell enumeration. The study is designed to detect a 25% improvement in the primary endpoint (α = 0.2, β = 0.1). The study was initiated December, 2012. Clinical trial information: NCT01681433.
A phase I/II study of the vascular disrupting agent BNC105P in combination with gemcitabine-carboplatin in partially platinum-sensitive ovarian cancer patients in first or second relapse: An international collaborative group trial of ANZGOG and HOG.
Authors: Rischin Danny , Matei Daniela , Goh Jeffrey C. , Vaughan Michelle Margaret , Beale Philip James , Tenney Meaghan Elizabeth , Martyn Julie , Sommeijer Dirkje Willemien , Iglesias Jose Luis , Bibby David C. , Simpson Jeremy , Doolin Elizabeth E. , Williams Corinne E. , Stockler Martin R. ,   Australia New Zealand Gynaecological Oncology Group (ANZGOG)
Published: March 2020

TPS5612 Background: BNC105P is a tubulin polymerization inhibitor and a vascular disrupting agent (VDA). In vivo exposure to BNC105P leads to selective damage of tumor vasculature in both primary and metastatic lesions, causing disruption of blood flow to tumors, hypoxia, and associated tumor necrosis. BNC105P also has a direct anti-proliferative action on cancer cells, including ovarian cancer cell lines. Pre-clinical data has demonstrated synergistic activity of BNC105P when combined with platinum or with gemcitabine, supporting the proposed study design. This study will determine the safety and efficacy of BNC105P in ovarian cancer when used in combination with gemcitabine-carboplatin. The target population is women with ovarian or primary peritoneal cancers who progressed 4 to 9 months after first-line platinum based chemotherapy, or 4 to 12 months after second line platinum based chemotherapy. Methods: A single arm phase I will be used to determine the phase II dose for the triplet combination (3-6 subjects per dose level, maximum of 24 subjects). Four dose levels of BNC105P (12-16 mg/m2) and gemcitabine (800-1000 mg/m2) will be assessed. The dose of carboplatin will be set at AUC 4. Enrolment to cohort 2 started in January 2013. The phase II component will consist of a 2-arm, randomized (1:1) study of BNC105P, gemcitabine and carboplatin versus gemcitabine and carboplatin alone. The primary endpoint for the phase II trial is objective response rate (ORR, according to RECIST 1.1 and/or GCIG CA125 criteria. An ORR of 40% or more with the experimental regimen would be considered worthy of further investigation, assuming an ORR of 20% with the control regimen. 110 phase II participants are planned (N = 55/arm). Treatment allocation will be balanced using minimization for the study site, target lesions according to RECIST (present vs. absent), progression free interval from last platinum based chemotherapy regimen (<6 months vs 6 months or more), and first relapse vs. second relapse. Biomarker (tissue and blood-borne) sampling and PK analysis will also be undertaken. Clinical trial information: NCT01624493.
PARAGON: Phase II study of aromatase inhibitors in women with potentially hormone responsive recurrent/metastatic gynecologic neoplasms: ANZGOG 0903.
Authors: Friedlander Michael , Sjoquist Katrin Marie , Sommeijer Dirkje Willemien , Bailey Lisa , Martyn Julie , Gillies Kim , Mileshkin Linda R. , O'Connel Rachel , Gebski Val , Vaughan Michelle Margaret , Blomfield Penny , Beale Philip James , Quinn Michael , Stockler Martin R. , Lombard Janine Margaret , Hadley Alison Maree , Amant Frederic , Edmondson Richard J ,   Australia New Zealand Gynaecological Oncology Group
Published: March 2020

TPS5614 Background: Many gynaecological cancers of different pathological type express estrogen and/or progesterone hormone receptors (ER/PR). Reports of tumour response and clinical benefit with hormonal therapies show variable rates of activity. There is a need to prospectively study the role of aromatase inhibitors in women with potentially hormone responsive recurrent gynaecological cancers to establish response rates, clinical benefit, quality of life (QoL) and identify predictors of response. Methods: PARAGON is phase II Gynecologic Cancer InterGroup trial lead by the Australia New Zealand Gynaecological Oncology Group, Cancer Research UK and the Belgian Gynaecological Oncology Group. The study is designed to facilitate research in rare tumours. The protocol allows postmenopausal women with recurrent gynaecological cancers to enrol into one of 7 subgroups; epithelial ovarian cancer (EOC) with only rising CA125 after first line chemotherapy, platinum resistant/refractory EOC, low grade EOC, endometrial carcinomas, endometrial stromal sarcomas, miscellaneous sarcomas and granulosa cell tumours and other sex cord stromal tumours. ER/PR positivity must be confirmed by immunohistochemistry. Each subgroup will enrol 25-50 patients with defined stopping rules based on response and reviewed by independent data monitoring committee (IDMC). Eligible patients receive 1 mg anastrozole daily until disease progression or unacceptable toxicity. Primary objective: clinical benefit (partial or complete response or stable disease). Secondary objectives: progression free survival, response duration, QoL, toxicity. Blood and tumour samples are being collected for translational studies and confirmation of ER/PR positivity. Recruitment commenced in 2011 in Australia, New Zealand and the United Kingdom. One hundred and fourteen of 350 planned patients have been enrolled to January 2013. In November 2012 IDMC recommended continuing recruitment to the EOC with rising Ca125 only and resistant/refractory subgroups based on review of activity outcomes for the first 25 patients. The trial will open in Belgium in April 2013. ACTRN12610000796088 Clinical trial information: 12610000796088.
Dovitinib as second-line therapy in patients with fibroblast growth factor receptor 2 (FGFR2)-mutated or non-mutated advanced and/or metastatic endometrial cancer (EC): A single-arm, multicenter, phase II study.
Authors: Konecny Gottfried E. , Finkler Neil , Garcia Agustin , Raspagliesi Francesco , Lopez Carolina Muriel , McCollum Michael , Rubio M Jesus , Squires Matthew , Pirotta Nicoletta , Upalawanna Allison , Yovine Alejandro Javier , Rocconi Rodney Paul 
Published: March 2020

TPS5616 Background: Despite the use of combination chemotherapy and introduction of novel targeted agents, the prognosis for advanced and/or metastatic EC is challenging. The occurrence of somatic activating FGFR2 mutations in EC suggests an opportunity for testing FGFR inhibitors. Dovitnib (DOV) is a potent receptor tyrosine kinase inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor and FGFR. The objective of the study is to investigate the efficacy and safety of DOV as second-line therapy in patients (pts) with advanced and/or metastatic EC. Methods: This multicenter, non-randomized, open label, single-arm, phase II study (NCT01379534) will enroll adult female pts (N~80) with either FGFR2 mutated (group 1) or non-mutated (group 2) histologically confirmed advanced and/or metastatic EC, who have documented radiological evidence of progressive disease (RECISTv1.1) after 1 prior line of chemotherapy, excluding adjuvant therapy. Eligible pts also need to have ≥1 measurable lesion (RECISTv1.1) and ECOG performance status ≤ 2. Pts will receive oral DOV of 500 mg/day, on a 5-days-on / 2-days-off dosing schedule until disease progression, unacceptable toxicity, death, or discontinuation due to any other reason. Primary endpoint is 18-week progression-free survival (PFS) rate (local review; RECIST v1.1) and secondary endpoints include overall response rate, disease control rate, duration of response, PFS, overall survival, safety, tolerability, pharmacokinetics, and pharmacodynamic effect of DOV on soluble plasma biomarker expression level. A 2-stage design with Bayesian interim monitoring (interim for futility analyses) will be used in each group. For stage 1, 20 pts will be enrolled into each group. If ≥ 8 of the first 20 pts with measurable disease at baseline in either group are progression-free after 18 weeks of treatment, 20 additional pts will be enrolled into that group in stage 2. Preliminary results for each group will be evaluated in the interim analysis. As of 20 January 2013, 43 pts have been enrolled (12 with and 31 without FGFR2 mutations). Clinical trial information: NCT01379534.
Pharmacodynamic study of neoadjuvant vemurafenib (VEM) in patients (pts) with BRAF mutated, locally advanced papillary thyroid cancer (PTC).
Authors: Cabanillas Maria E. , Holsinger F. Christopher , Sturgis Erich M. , Habra Mouhammed Amir , Davies Michael A. , Munsell Mark F. , French Jena , Busaidy Naifa , Hu Mimi I-Nan , Sherman Steven I. 
Published: March 2020

TPS6100 Background: BRAF mutations are found in 40% of pts with newly diagnosed PTC but much more prevalent in recurrent PTC, ranging from 78-86%, suggesting they play an active role in tumor progression. Activating mutations in BRAF result in constitutive activation of MEK and subsequently ERK. ERK mediates activation of nuclear transcription factors coordinating expression of genes involved in proliferation and survival of malignant cells. PTC usually has an excellent prognosis, especially in younger pts and in pts who respond to the only effective treatment: surgery followed by radioactive iodine (RAI). However, more advanced stage disease at diagnosis, older age, and lack of RAI avidity are associated with a high rate of recurrence and distant metastasis, imparting a worse overall survival. Long-term outcomes depend highly on initial surgery outcome. Pts at highest risk of recurrence and death are those with gross residual disease after surgery and macroscopic tumor invasion. VEM is an inhibitor of the activated form of the BRAF serine-threonine kinase enzyme. The drug is FDA approved for the treatment of advanced melanoma and is currently being studied in a phase 2 trial in metastatic BRAF-mutated PTC. This is a neoadjuvant trial to determine if pharmacodynamic changes in the tumor correlate with response to drug. Methods: Pts with primary or recurrent BRAF mutated PTC who are planned for surgical resection are eligible. Pts will undergo baseline core biopsy prior to starting VEM 960mg bid. After 56 days of treatment they will undergo surgery and post-treatment specimen will be collected. Pts with widely metastatic PTC may continue VEM. The primary endpoint is to determine whether changes in ERK phosphorylation responses after treatment with VEM correlate with clinical response at day 56 in pts with locally advanced, BRAF mutated PTC. Secondary endpoints include assessments of safety of neoadjuvant VEM, response by RECIST, rate of surgical complications, persistent disease at the surgical site at 1 year, and mechanisms of resistance to VEM. The trial began enrolling pts in December 2012, with a total of 22 pts planned. This trial has no sponsor. Clinical trial information: NCT01709292.
ADAPT: Adjuvant dynamic marker-adjusted personalized therapy trial optimizing risk assessment and therapy response prediction in early breast cancer.
Authors: Harbeck Nadia , Hofmann Daniel , Gluz Oleg , Kates Ronald E. , Kümmel Sherko , Nuding Benno , Rezai Mahdi , Kusche Manfred , Schumacher Claudia , Nitz Ulrike 
Published: March 2020

TPS655^ Background: Indication of (neo-)adjuvant therapy is based on risk profile, hormone receptor and HER2 status at time of primary diagnosis. Data indicate dynamic proliferation changes after short-term induction therapy are superior to static initial biopsy results in predicting outcome and tumor response following neoadjuvant CTx in distinct BC subtypes. First generation trials such as TAILORx, MINDACT, NNBC-3, WSG planB utilize information of new prognostic/predictive tests to reduce overtreatment by CTx. Results still pending. ADAPT is a second generation trial addressing individualization of adjuvant decision-making in early BC by utilizing optimized pre-therapeutic biomarker information and early biomarker changes in a second core biopsy after 3-week subtype specific induction therapy. It aims at reducing over-/undertreatment in luminal tumors and optimizing therapy in HER2+ (T-DM1, pertuzumab) / TNBC (nab-paclitaxel + platinum/gemcitabine). Methods: Design: ADAPT combines static prognosis assessment by conventional markers (nodal status) and Recurrence Score (HR+) with dynamic measurement of proliferation changes after a short 3-week induction therapy, using the baseline diagnostic and repeat core biopsy following induction. ADAPT is a prospective, multi-center, controlled, non-blinded, randomized phase II/III trial, comprising an umbrella trial and 4 sub-trials (HR+/HER2-, HR+/HER2+, HR-/HER2+, TNBC). Eligibility criteria: Pre-/postmenopausal women with histologically confirmed unilateral primary invasive BC. Pts requiring CTx/targeted therapy with no contraindications. Statistics: Assumption across sub-protocols: CTx spared in 1120 HR+/HER2-, pCR achieved in 170 HER2+/TNBC pts. Outcome of good-proliferation responders/pCR pts will be compared to reference group (n=640 HR+/HER2- pts: low RS, no CTx, 94% 5yr survival). One-sided test of non-inferiority (3.2% margin, 90.8%) with alpha=0.05 will have 80% power. Present/target accrual:By 01/2013: 16/35 sites initiated. ADAPT HR+/HER2-: 161/4000 pts recruited. ADAPT HER2+/HR+: 9/380 pts recruited. ADAPT HER2+/HR- or TNBC: start of recruitment planned for Q2 2013. Clinical trial information: NCT01781338.
A phase II, dose-optimization trial of autologous T cells genetically engineered to express anti-CD19 chimeric antigen receptor (CART-19) in patients with relapsed or refractory (r/r) CD19+ chronic lymphocytic leukemia (CLL).
Authors: Porter David L. , Frey Noelle V. , Loren Alison W. , Levine Bruce , Kalos Michael , McConville Holly , Gilmore Joan , Chew Anne , Shen Angela , So Charlene , Sharr Michele , Wood Patricia Ann , June Carl H. 
Published: March 2020

TPS7132 Background: The poor prognosis and lack of effective treatment options for patients with r/r CLL highlight the need for novel therapies in this setting. CD19 is a promising anticancer target because it is broadly expressed on normal and malignant B cells through several stages of maturation but absent on pluripotent stem cells. CART-19 (CTL019) therapy involves adoptive transfer of autologous T cells genetically modified via lentiviral transduction to express chimeric antigen receptors (CAR) designed to target CD19+ cells. CART-19 cells express a CD19 antigen recognition domain combined with intracellular signaling domains, CD137 (4-1BB) and CD3-zeta, which mediate cytolytic T-cell activity. In patients with r/r CLL, CART-19 therapy showed potent antileukemic activity with long-term persistence of transduced cells at doses from 1.4 × 107 to 1.1 × 109 CART-19 cells. As of August 2012, 3 of 8 evaluable CLL patients achieved CR (two > 24 months and one > 5 months) and remain in CR with detectable CART-19 cells. Two patients had PR lasting 3 and 5 months, and 3 patients did not respond (Porter et al. NEJM. 2011; Kalos et al. Sci Transl Med. 2011; Porter et al. ASH 2012). Here, we describe a study to determine the optimal dose of CART-19 cells (NCT01747486). Methods: Adults with relapsed or persistent CLL or SLL after ≥ 2 previous therapies will undergo leukapheresis to obtain T cells, which will be stimulated, expanded, and lentivirus transduced ex vivo to express the CD19/4-1BB/CD3-zeta CAR. Patients will undergo lymphodepletion chemotherapy prior to infusion of CART-19 cells. In stage I of the II-stage trial, 30 patients will be randomized 1:1 and receive either 1-5 × 108 or 1-5 × 107 CART-19 T cells. The optimal dose in stage I will be selected based on clinical responses, feasibility, and tolerability. In stage II, 8 additional patients will be enrolled into the selected dose cohort. Study objectives are to determine the efficacy (CR rate within 3 months) and safety (CTCAE v 4.0) of each dose, in vivo CART-19 expansion, and manufacturing feasibility. Three patients have been enrolled as of January 2013. Clinical trial information: NCT01747486.
A phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of idelalisib (GS-1101) in combination with bendamustine and rituximab for previously treated chronic lymphocytic leukemia (CLL).
Authors: Eradat Herbert Aaron , Coutre Steven E. , Barrientos Jacqueline Claudia , Rai Kanti Roop , Farber Charles Michael , Hillmen Peter , Sharman Jeff Porter , Ghia Paolo , Coiffier Bertrand , Walewski Jan Andrzej , Berneman Zwi N. , O'Brien Susan Mary , Brown Jennifer R. , Peterman Sissy , Dansey Roger D. , Jahn Thomas Michael , Cramer Paula , Hallek Michael J. 
Published: March 2020

TPS7133 Background: PI3K-delta is critical for the activation, proliferation and survival of B cells and plays a role in homing and retention of B cells in lymphoid tissues. PI3Kδ signaling is hyperactive in many B-cell malignancies. Idelalisib is a first-in-class, selective, oral inhibitor of PI3Kδ that reduces proliferation, enhances apoptosis, and alters trafficking of malignant B cells in lymphoid tissues (Lannutti, 2011). Phase 1 trials demonstrated that idelalisib is highly active in heavily pretreated pts with CLL as a single agent or in combination with rituximab (R), bendamustine (B), or BR: pts experienced reductions in disease-associated chemokines, profound and rapid reductions in lymphadenopathy, and durable clinical benefit with an acceptable safety profile (Coutre et al, 2012; Sharman et al, 2011). Methods: Study will enroll 390 pts with previously treated CLL who have measurable lymphadenopathy, have received prior therapy containing a purine analog or B and an anti-CD20 monoclonal antibody, are not refractory to B, have experienced CLL progression within 36 months from the completion of the last prior therapy, and are currently sufficiently fit to receive cytotoxic therapy. Pts are randomized in a 1:1 ratio to Arm A or B. On Arm A, subjects receive idelalisib continuously at 150 mg BID + R at 375 mg/m2 (1st dose) and then 500 mg/m2 every 4 weeks for 6 cycles + B at 70 mg/m2 on Days 1 and 2 of each 4-week cycle for 6 cycles. On Arm B, subjects receive placebo instead of idelalisib. Stratification factors address IGHV mutational status, del(17p)/p53 mutation status, and refractory vs relapsed disease. The primary endpoint is PFS and key secondary endpoints include ORR, lymph node response rate, CR rate, and OS. This is an event-driven trial and primary endpoint evaluation will be based on independent central review. For the primary efficacy analysis, the difference in PFS between the treatment arms will be assessed in the ITT analysis set. The study was initiated in June 2012 and a data monitoring committee has begun regular review of data. Clinical trial information: NCT01569295.
A phase II single-arm study of LDK378 in patients with ALK-activated (ALK+) non-small cell lung cancer (NSCLC) previously treated with chemotherapy and crizotinib (CRZ).
Authors: Shaw Alice Tsang , Mok Tony , Spigel David R. , Nishio Makoto , Felip Enriqueta , Tan Daniel Shao-Weng , Garcia-Campelo M. Rosario , Groen Harry J.M. , Dakhil Shaker R. , Schaefer Eric Scott , Farrell Nicholas John , Blakesley Rick E. , Weir Alexander , Ristic Mirta , Selvaggi Giovanni , Scagliotti Giorgio 
Published: March 2020

TPS8119 Background: NSCLC harboring anaplastic lymphoma kinase (ALK) gene rearrangements (2–8% of cases) are sensitive to CRZ, the only approved ALK inhibitor, but invariably develop resistance. There are currently no standard ALK-targeted treatments for CRZ-resistant ALK+ NSCLC. LDK378 is a novel, oral ALK inhibitor with 20-fold greater potency than CRZ in enzymatic assays. In an ongoing phase I trial, LDK378 has demonstrated substantial clinical activity in patients (pts) with ALK+ NSCLC whose disease has failed CRZ. At a dose ≥400 mg (45 pts), the overall response rate (ORR) was 80%, with 47% confirmed responses (data cutoff August 31, 2012). Nausea, vomiting, diarrhea and fatigue were the main toxicities. The recommended phase II dose is 750 mg daily. Methods: This phase II multicenter, open label, single-arm study (CLDK378A2201) is designed to evaluate the efficacy and safety of oral LDK378 750 mg once-daily in pts with ALK+ (by FDA-approved FISH test) advanced NSCLC. Pts must have received cytotoxic chemotherapy (1–3 lines, including 1 platinum doublet) and progressed on CRZ as the last therapy prior to study entry. Pts with ECOG PS 0–2 and stable CNS metastases are eligible. LDK378 may be continued beyond RECIST-defined PD if there is evidence of clinical benefit. The primary objective is to assess the antitumor activity of LDK378 in terms of ORR by investigator assessment (using RECIST v1.1). Secondary/exploratory objectives include evaluating response endpoints (duration of response, time to response and ORR by independent radiological review), PFS, OS, safety, PK, and impact on patient-reported outcomes. The primary analysis will occur when all pts have completed 6 cycles or discontinued treatment earlier. The study design (137 pts) provides 90% power to test a null hypothesis of ORR ≤25% vs. a target ORR of ≥38%: if ≥45 responses are observed (estimated ORR 33%), the null hypothesis will be rejected at a one-sided significance level of 0.025. The study is recruiting in 67 sites from 14 countries across Europe, Asia and North America. As of February 5, 2013, 7 pts have been enrolled. ClinicalTrials.gov identifier NCT01685060. Clinical trial information: NCT01685060.