bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 2, open-label, multicenter study of the efficacy and safety of INCB054828 in patients (pts) with advanced, metastatic, or surgically unresectable cholangiocarcinoma (CCA) with inadequate response to prior therapy.
Authors: Borad Mitesh J. , Davis Sarah Lindsey , Lowery Maeve Aine , Lihou Christine F. , Abou-Alfa Ghassan K. 
Published: September 2018

TPS4145 Background: Dysregulation of fibroblast growth factor receptor (FGFR) signaling by FGFR translocations and activating mutations is implicated in many cancers, including CCA. FGFR2 translocation, the most common FGFRalteration, occurs in ~13% of pts with intrahepatic CCA. INCB054828 is a novel, orally available, selective inhibitor of FGFR1, FGFR2, and FGFR3 tyrosine kinase activity (AACR 2015; Abstract 771). Methods: This phase 2, open-label trial will evaluate INCB054828 monotherapy in pts with advanced/metastatic or unresectable CCA (NCT02924376). Pts will be prescreened locally or centrally for FGF/FGFR status prior to enrollment (Table): FGFR2 translocation (Cohort A); other FGF/FGFR alteration (Cohort B); no FGF/FGFR alteration (Cohort C; negative control for effects of FGF/FGFR alteration on objective response rate [ORR]). Eligibility criteria include: age ≥18 years; ECOG performance status ≤2; adequate liver and renal function; life expectancy ≥12 wks; disease progression after ≥1 prior systemic therapy; no prior use of selective FGFR inhibitors. Pts will self-administer INCB054828 orally at a starting dose of 13.5 mg QD on a 21-day cycle (2 wks on; 1 wk off); treatment will continue until disease progression or unacceptable toxicity. The primary endpoint will be ORR (complete or partial response, independent radiologic review committee, RECIST v1.1) in pts with FGFR2 translocation (Cohort A). Secondary endpoints include ORR in pts positive or negative for any FGF/FGFRalteration and duration of response, PFS, OS, and safety (all cohorts). The study has currently enrolled 2 pts (recruitment ongoing; estimated primary completion, April 2018). Clinical trial information: NCT02924376. [Table: see text]
P3BEP (ANZUP 1302): An international randomised phase 3 trial of accelerated versus standard BEP chemotherapy for adult and paediatric male and female patients with intermediate and poor-risk metastatic germ cell tumours (GCTs).
Authors: Grimison Peter S. , Lawrence Nicola Jane , Stockler Martin R. , Martin Andrew James , Yip Sonia , Wong Nicole , Yeung Annie , Friedlander Michael , Mazhar Danish , Pashankar Farzana , Quinn David I. , Walker Rick , Winstanley Mark , Hanning Fritha J. , Weickhardt Andrew James , Stevanovic Amanda Gwendolyn , Davis Ian D. , Toner Guy C. ,   Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Published: September 2018

TPS4592 Background: Bleomycin, etoposide, cisplatin (BEP) administered 3-weekly x 4 remains standard 1st line chemotherapy for metastatic GCTs. Accelerating regimens by giving them 2-weekly rather than 3-weekly has improved cure rates in other cancers. This is the first international randomised clinical trial for intermediate and poor-risk metastatic extra-cranial GCTs involving both adult and paediatric age groups open to both males and females. We aim to determine if accelerated BEP is superior to standard BEP. Methods: DESIGN: Open-label, randomised, stratified multicentre, 2 stage, phase 3 trial. Primary endpoint for stage I (n = 150) is complete response rate (RR), and for entire trial (n = 500) is progression free survival (PFS). SAMPLE SIZE: 150 and 500 patients gives > 80% power to detect a 20% improvement in RRs and 7% absolute improvement in 2yr PFS, respectively. POPULATION: Males and females aged 11-45 yrs with intermediate or poor-risk metastatic GCTs of the testis, ovary, retroperitoneum or mediastinum for 1st line chemotherapy. TREATMENT:Randomisation 1:1 to 4 cycles of “standard BEP” or “accelerated BEP”: cisplatin 20mg/m2 IV days 1-5; etoposide 100mg/m2 IV days 1-5; bleomycin 30000 IU IV weekly; and pegylated G-CSF 6mg SC on Day 6; given every 3 weeks or every 2 weeks respectively. Accelerated BEP arm receives 4 additional weekly doses of bleomycin. ASSESSMENTS: Response assessments at 30-day safety assessment, and 6 months from randomisation or after all post-chemotherapy intervention is completed. Regular follow-up to 5 years, then annually. Archival tumour tissue and baseline blood collected for translational substudies. STATUS: 27 sites open in ANZ, 34 patients recruited by February 2017. International collaborations with UK (led by Cambridge Clinical Trials Unit) and US (led by Childrens Oncology Group) confirmed with sites expected to open by early 2017, and more sites sought for stage 2. Funded by Cancer Council Australia and Cancer Australia. ANZUP supported by Cancer Australia and previously CINSW. ANZCTR: ACTRN12613000496718. Clinical trial information: NCT02582697.
Trial of rucaparib in prostate indications 3 (TRITON3): An international, multicenter, randomized, open-label phase 3 study of rucaparib vs physician’s choice of therapy for patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC) associated with homologous recombination deficiency (HRD).
Authors: Ryan Charles J. , Watkins Simon Paul , Despain Darrin , Karlovich Chris Alan , Simmons Andrew , Golsorkhi Anthony A. , Chowdhury Simon 
Published: September 2018

TPS5087 Background: Pts with mCRPC often initially receive androgen receptor-targeted therapy (eg, abiraterone or enzalutamide), but they almost always progress. Poly(ADP-ribose) polymerase (PARP) inhibitors (eg, olaparib) have demonstrated clinical activity in pts with mCRPC with a deleterious mutation in a homologous recombination (HR) DNA repair gene; 14 of 16 evaluable pts with mCRPC and a tumor alteration in an HR gene, including BRCA1, BRCA2, and ATM, responded to olaparib (Mateo et al. N Engl J Med. 2015;373:1697-708). The PARP inhibitor rucaparib is approved in the US for treatment of pts with ovarian carcinoma that harbors a deleterious BRCA1 or BRCA2 mutation (germline and/or somatic) who have received ≥2 chemotherapies. These data support investigating rucaparib as a treatment option in pts with mCRPC with HRD. Methods: TRITON3 (NCT02975934)is a phase 3 study evaluating rucaparib (600 mg BID) vs physician’s choice (abiraterone, enzalutamide, or docetaxel) in pts with mCRPC who have a deleterious germline or somatic mutation in BRCA1, BRCA2, or ATM as determined by local and/or central testing. All pts must have progressed on abiraterone or enzalutamide in the mCRPC setting; pts who received prior chemotherapy for mCRPC or PARP inhibitor treatment are excluded. Pts will be randomized 2:1 to rucaparib or physician’s choice of comparator therapy; pts randomized to physician’s choice may cross over to rucaparib on radiographic progression confirmed by independent radiology review (IRR). The primary endpoint is IRR-confirmed radiographic progression-free survival (modified RECIST version 1.1/PCWG3 criteria). Secondary objectives include overall survival, objective response rate, duration of response, clinical benefit rate, pt-reported outcomes, and safety. Pretreatment blood samples will be collected from all pts to enable development of a plasma-based companion diagnostic to identify pts who may benefit from rucaparib treatment. Pts (≈400) will be enrolled at > 100 sites worldwide. Clinical trial information: NCT02975934.
A phase II randomized trial of observation versus stereotactic ablative radiation for oligometastatic prostate cancer (ORIOLE).
Authors: Phillips Ryan , Radwan Noura , Ross Ashley , Rowe Steven P. , Gorin Michael A. , Antonarakis Emmanuel S. , Deville Curtiland , Greco Stephen C , Denmeade Samuel R. , Paller Channing Judith , Song Daniel Y. , Diehn Maximilian , Wang Hao , Carducci Michael Anthony , Pienta Kenneth J. , Pomper Martin G. , DeWeese Theodore L. , Dicker Adam P. , Eisenberger Mario A. , Tran Phuoc T. 
Published: September 2018

TPS5094 Background: ORIOLE is a randomized, non-blinded Phase II interventional study evaluating the safety and efficacy of SBRT in biochemically recurrent, oligometastatic, hormone-sensitive prostate cancer at 3 centers in the US. Patients will be stratified by clinical characteristics and randomized 2:1 to SBRT or observation. The primary clinical endpoint is progression at 6 months defined by PSA increase, radiologic or clinical evidence, ADT initiation, or death from any cause. Secondary endpoints include local control at 6 months, SBRT-associated toxicity and quality of life, and ADT-free survival. Imaging and laboratory correlates will characterize, in isolation, the effects of SBRT on oligometastatic disease. Methods: Eligible patients are hormone-sensitive, have undergone prior definitive treatment and recurred with 1-3 asymptomatic bone or soft tissue metastases diagnosed within 6 months, PSA doubling time (PSADT) < 15 months, ECOG performance status ≤ 2, and normal organ and marrow function. Minimization will be used to balance assignment by primary intervention, prior ADT, and PSADT. Accrual of 54 patients provides 85% power to detect a decrease in progression rate from 80% to 40% with type I error = 0.05 using one-sided Fisher’s exact test. Hazard ratios and Kaplan-Meier estimates of progression free survival, ADT free survival, and time to locoregional and distant progression will be calculated based on intention-to-treat. Local control will be assessed using RECIST 1.1 criteria. Withdrawal prior to 6 months will be counted as progression. Adverse events will be summarized and quality of life pre- and post-SBRT will be measured by Brief Pain Inventory. The investigational targeted imaging agent 18F-DCFPyL will be compared to bone scan and CT for identifying oligometastases before SBRT and monitoring disease response following SBRT. Biological alterations induced by SBRT will be investigated using circulating tumor cell analysis, deep sequencing of circulating tumor DNA, and T-cell repertoire profiling. A hereditary cancer assay will inform efforts to advance personalized screening and therapy. Clinical trial information: NCT02680587.
Combination chemotherapy with nintedanib/placebo for patients with advanced or recurrent endometrial cancer: The NSGO ENGOT-EN1/FANDANGO trial.
Authors: Mirza Mansoor Raza , Maenpaa Johanna Unelma , Braicu Elena Ioana , Vergote Ignace , Berton-Rigaud Dominique , Rosenberg Per , Huober Jens Bodo , Denys Hannelore , Joly Lobbedez Florence , Kristensen Gunnar , Reimer Toralf , Kridelka Frederic , Floquet Anne , Knudsen Anja , Aktas Bahriye , Baurain Jean-Francois , Follana Philippe , Juhler-Nøttrup Trine , Jederud Christina , Sehouli Jalid 
Published: September 2018

TPS5611 Background: Endometrial cancer (EC) patients with advanced and recurrent disease relapse despite treatment with combination chemotherapy and have a short progression-free survival (PFS). With the emerging clinical data on anti-angiogenic agents and with promising results of nintedanib in ovarian cancer, it is apparent to explore its role in EC. Nintedanib is a potent, orally available triple receptor tyrosine kinase inhibitor targeting VEGFR 1-3, PDGFR α/β, and FGFR 1-3. This placebo-controlled, multicenter, two-arm, phase 2 trial compares nintedanib versus placebo as concomitant and maintenance therapy in combination with chemotherapy in patients with advanced or recurrent EC. Methods: The primary objective of this trial is to evaluate efficacy of nintedanib against placebo in combination with chemotherapy, defined by PFS. Key eligibility criteria include: histologically confirmed EC, stage 3C 2 or 4 A & B or relapsed after adjuvant therapy for stage 1-3 disease; prior surgery; adjuvant chemotherapy; radiation therapy; hormonal therapy are permitted; measurable/non-measurable disease. 148 patients will be randomized 1:1 to receive nintedanib 200mg twice daily or placebo days 2-21 during chemotherapy (six cycles of Carboplatin (AUC5) and paclitaxel (175mg/m2) every 21 days) and continuously in maintenance phase. Nintedanib/placebo is continued until disease progression, unacceptable toxicity, or withdrawal. Secondary endpoints include PFS in sub-populations, PFS2, disease specific survival, time to first subsequent therapy, time to second subsequent therapy, overall survival, objective response, disease control rate, patient reported outcoms (assessed via EORTC QLQ-C30 and EORTC QLQ-EN24) and safety. Trial is enrolling patients. The following cooperative groups are participating: NSGO (DK, FIN, SWE, NOR), NOGGO (GER), BGOG (BEL), & GINECO (FRA). Clinical trial information: NCT02730416.
ABC trial (A011502): A randomized phase III double blinded placebo controlled trial of aspirin as adjuvant therapy for node positive breast cancer.
Authors: Chen Wendy Y. , Winer Eric P. , Barry William Thomas , Hudis Clifford A. , Openshaw Thomas H. , Visvanathan Kala , Symington Banu , Matyka Carol , Holmes Michelle D. 
Published: September 2018

TPS586 Background: In-vitro and in-vivo evidence suggest that aspirin, an inexpensive and widely available drug may have anti-tumor activity via effects on multiple pathways. Multiple epidemiologic studies have reported improved breast cancer survival among regular aspirin users compared to non-users. Furthermore, pooled data from randomized trials of aspirin for cardiovascular disease have also reported a decreased risk of metastatic cancer among aspirin users, especially metastatic adenocarcinoma (RR 0.52 (95% CI 0.35-0.75). In order for aspirin to be considered standard of care, the exact benefits and risks for breast cancer survivors need to be confirmed in a randomized trial. Methods: The primary objective is to compare the effect of aspirin versus placebo upon invasive disease-free survival (iDFS) in stage II-III node-positive HER2 negative breast cancer patients. Secondary objectives include effects on overall survival and cardiovascular disease and to collect toxicity and adherence. A biospecimen repository will be created for future correlative analyses including tumor collection at baseline and blood and urine samples at baseline and 2 years. Questionnaires assessing lifestyle factors associated with inflammation (pain, sleep, stress, and depression) will also be collected at baseline and 2 years. Study design: Subjects will be randomized (1:1) to aspirin 300 mg vs placebo daily for 5 years in a double-blinded fashion. Stratification factors include hormone receptor status (positive vs negative), body mass index ( < or ≥ 30 kg/m2), and stage (II vs III).Subjects will be followed every 6 six months while on study drug and then annually until 10 years from registration. 2936 patients will be enrolled with 80% power to detect HR 0.75. Eligibility: Eligible subjects include patients aged 18-70 diagnosed with a primary invasive stage II or III node positive HER2 negative breast cancer in the past year. Patients who currently use any oral or injectable anticoagulant or those with a prior history of GI bleeding, atrial fibrillation, myocardial infarction, or grade IV hypertension will be excluded. Patients who regular used aspirin over the past year will be excluded. Clinical trial information: NCT02927249.
Anti-PD-L1 durvalumab combined with cetuximab and radiotherapy in locally advanced squamous cell carcinoma of the head and neck: A phase II study.
Authors: Bonomo Pierluigi , Desideri Isacco , Loi Mauro , Mangoni Monica , Sottili Mariangela , Greto Daniela , Scotti Vieri , Meattini Icro , Livi Lorenzo 
Published: September 2018

TPS6094 Background: Head and neck squamous cell carcinoma (HNSCC) is characterized by prominent immune escape mechanisms. Potentially, the blockade of immune check points such as the PD-1/PD-L1 axis may stimulate the host T-cell activation against tumor cells and favor the FcγRIIIa-mediated, Cetuximab (CTX) induced antibody dependent cellular cytoxicity (ADCC). Durvalumab (DUR) is a humanized monoclonal IgG1, anti-PD-L1 antibody with promising activity in recurrent/metastatic HNSCC (NCT01693562). The aim of our study is to test the hypothesis that a restored ability of the host immune system via blockade of the PD1/PD-L1 axis through DUR may enhance the antitumor activity of both CTX and radiotherapy (RT) in locally advanced HNSCC, a setting with unmet needs for effective treatment options. Methods: In this open-label, multi-center, single-arm, phase II study, enrolled patients will receive RT (69.9 Gy/2.12 Gy fx in 33 fractions over 7 weeks) with concurrent CTX (400 mg/m2 1 week before RT start followed by 250 mg/m2 q1w) and DUR (1500 mg q4w starting from RT-CTX week 1) followed by adjuvant DUR (to a maximum of 6 months after completion of RT-CTX). Primary endpoint of the study is 2-year progression-free survival (PFS). Assuming a 2-year PFS of 66% based on historical data from RTOG study 0129, the experimental regimen is hypothesized to yield a 12% absolute increase at 2 years, corresponding to a hazard ratio of 0.6 (α = 0.1, power is 0.80 when the 2-year PFS is 78%). The required sample size with this design is 69 patients. A safety run-in is planned after the enrollment of first 12, 24 and 36 patients. Patients affected by high-risk ( > N2a or > T3, any N) larynx, hypopharynx and HPV negative oropharynx or HPV-positive oropharynx ( > N2b, > 10 pack/years) will be eligible. To avoid potential RT-induced chronic loco-regional immunosuppression, protocol-indications will be undertaken to restrict target volumes to sites of gross disease and subclinical high risk lymph node basins excluding areas deemed at very low risk of disease spread. For this purpose, dose-painting intensity modulated radiotherapy (IMRT) is mandatory for this study. Clinical trial information: 2016-004668-20.
A randomized, double-blind phase III study of ibrutinib versus placebo in combination with corticosteroids in patients with new onset chronic graft versus host disease.
Authors: Miklos David Bernard , Jagasia Madan H. , Greinix Hildegard , Ko Bor-Sheng , Jacobsohn David A. , Mokatrin Ahmad , Dubovsky Jason , Horn Biljana , Hauns Bernhard , Styles Lori Appel , Flowers Mary 
Published: September 2018

TPS7072 Background: Chronic graft versus host disease (cGVHD) is a common complication of allogeneic stem cell transplantation, with pathophysiology involving alloreactive and dysregulated T and B cells and innate immune populations. Ibrutinib, a first-in-class, once-daily inhibitor of Bruton's tyrosine kinase, is indicated by the US FDA for the treatment of patients (pts) with CLL/SLL. Ibrutinib recently received breakthrough therapy and orphan drug designation for the treatment of pts with cGVHD who did not respond to one or more lines of systemic therapy. Ibrutinib reduces severity of cGVHD in murine models and recently was shown to achieve an NIH-defined overall response rate of 67% in pts with steroid relapsed/refractory cGVHD (Miklos Blood 2016). Methods: The primary objective of this Phase 3, multicenter, international, randomized, controlled, double-blind study is to evaluate the 24-week response rate of ibrutinib versus placebo in combination with prednisone. Pts with newly diagnosed moderate or severe cGVHD, as per NIH Consensus Development Project Criteria (2014), will be randomized in a 1:1 ratio to receive either oral ibrutinib (arm A) or placebo (arm B) in combination with oral prednisone. Ibrutinib or placebo will be given until unacceptable toxicity, relapse of underlying disease, death, or the need for a new systemic treatment for progressive cGVHD. Eligible study pts (age ≥12 yrs) must require systemic treatment with corticosteroids and have no prior systemic treatment for cGVHD. The primary endpoint is response rate (complete or partial response) at 24 weeks, as per NIH Consensus Development Project Criteria, and must occur in the absence of both new therapy for cGVHD and relapse/return of the underlying disease that was the indication for transplant. Secondary endpoints will assess for additional clinical benefit including corticosteroid dose reduction, improvement of Lee cGVHD Symptom Scale scores, withdrawal of all immunosuppressants, and overall survival. This study is currently enrolling pts. Funding source: Pharmacyclics LLC, an AbbVie Company. Clinical trial information: NCT02959944.
A phase I trial of CD19-targeted EGFRt/19-28z/4-1BBL armored chimeric antigen receptor (CAR) modified T cells in patients with relapsed or refractory chronic lymphocytic leukemia.
Authors: Park Jae Hong , Riviere Isabelle , Wang Xiuyan , Senechal Brigitte , Bernal Yvette , Halton Elizabeth , Diamonte Claudia , Wang Yongzeng , Brentjens Renier J. , Sadelain Michel 
Published: September 2018

TPS7568 Background: Despite the recent progress in the therapy of CLL with BTK, PI3Kδ, and BCL2 inhibitors, CLL remains incurable and patients with high-risk disease features (i.e. del17p, complex karyotype) and patients whose disease progress after treatment with the above targeted agents continue to have extremely poor prognosis. CD19-specific chimeric antigen receptor (CAR) T cell therapy with various 2nd generation CARs (19-28z or 19-41BBz) have demonstrated anti-tumor efficacy in CLL but the complete response (CR) rates in CLL have been suboptimal (20-45%) compared to CR rates in ALL (80-90%). The suboptimal activity of the current 2nd generation CAR T cells can be due to the inhibitory tumor microenvironment (TM) of CLL. We believe one approach to over the hostile TM is through the use of CD19-CAR T cells further modified to express a second costimulatory ligand, 4-1BBL. A binding of 4-1BBL to its cognate receptor enhances T cell proliferation, IL-2 secretion, and survival and cytolytic activity of the T cells compared to 19-28z. 19-41BBz and 1928BBz (Zhao Z et al. Cancer Cell 2015;28:415-428). Methods: This phase I dose escalating trial is a single-center clinical trial (MSKCC) to study the safety and efficacy of autologous EGFRt/19-28z/4-1BBL+ CAR T cells in patients with relapsed CLL. Given the concern for potential systemic toxicity the vector includes a "safety switch" in the form of a gene for the expression of truncated form of human epidermal growth factor receptor (EGFRt). Patients with relapsed CLL are eligible for the trial. Patients will receive conditioning chemotherapy of cyclophosphamide followed by escalating doses of CAR T cells (1x105 – 3x106 CAR T cells/kg). The primary endpoint is safety and maximum tolerated doses of the CAR T ells. Secondary objectives include response assessment by iwCLL criteria. The comprehensive treatment algorithms for CRS and neurotoxicity are based on our CAR T cell experience in other studies. The study will begin enrollment in February 2017 and enroll up to 30 patients. Clinical trial information: Pending.