bluuebunny/crossref_metadata_2025_split huggingface dataset:
IFCT-GFPC-0701 MAPS trial, a multicenter randomized phase III trial of pemetrexed-cisplatin with or without bevacizumab in patients with malignant pleural mesothelioma (MPM).
Authors: Zalcman Gerard , Mazieres Julien , Scherpereel Arnaud , Margery Jacques , Moro-Sibilot Denis , Parienti Jean-Jacques , Gounant Valérie , Riviere Alain , Monnet Isabelle , Molinier Oliver , Lena Hervé , Friard Sylvie , Duhamel Jean-Paul , Audigier-Valette Clarisse , Robinet Gilles , Creveuil Christian , Ligeza-poisson Catherine , Morin Franck 
Published: March 2020

TPS7112 Background: MPM median OS does not exceed 13 months with pem/CDDP doublet. U.S. Intergroup phase II trial of gemcitabine/CDDP, with or without bevacizumab, gave an appealing 15.6 months median OS in the bevacizumab arm. French Intergroup aimed to test pem/CDDP with bevacizumab (PCB), in a randomized phase III trial. Methods: Eligible patients had unresectable histologically proved MPM, no prior chemo, PS 0-2, no thrombosis, nor bleeding. Primary endpoint: The primary outcome will be survival. The secondary endpoint will be Progression-Free Survival. Patients received pem 500 mg/m2, CDDP 75 mg/m2 (PC),at D1, and vitamin B12 +B9 substitution, with (arm B) or without bevacizumab (arm A), 15 mg/kg Q21D, for 6 cycles. Arm B nonprogressive patients received bevacizumab maintenance therapy until progression or toxicity. 445 patients to be recruited during a period 48 months, with at least 24 months of follow-up, and 385 events (deaths), will be needed to assure a power of 80% and detect at least a 4.3 months of median survival increase. This hypothesis leads to a Hazard Ratio (HR) of 1.33 and a 3-years survival of 14.7% in control arm and 23.6 % in experimental arm, with an absolute difference of 8.9% in survival rates. Accrual status: The first patient was included in February 2008. On January 31, 2012, 257 patients from 85 French centers had been enrolled. The end of accrual can be expected for September 2013. Ancillary studies: For molecular biomarker analyses, thoracoscopic tissue specimens (TS, ERCC1, MSH2, TUBB3, NF2, p16, RASSF1A methylation,15 microRNAs ) and blood samples (micro-RNAS, VEGF, osteopontin, SRMP) at diagnosis are centrally collected. Finally, a prospective study comparing PET-CT to standard CT with central blinded analysis, is currently on-going for evaluation of response, and accuracy of modified RECIST criteria for mesothelioma.
Pilot trial of molecular profiling and targeted therapies in advanced thoracic malignancies: Non-small cell lung cancer, small cell lung cancer and thymic malignancies (CUSTOM).
Authors: Lopez-Chavez Ariel , Rajan Arun , Thomas Anish , Raffeld Mark , Xi Liqiang , Meltzer Paul S. , Duffy Regan M. , Pack Svetlana , Sandler Alan , Corless Christopher L. , Killian Keith , Oberholtzer Carl , Abdullaev Zied , Giaccone Giuseppe 
Published: March 2020

TPS7609 Background: For decades, clinical trial design strategies have relied upon the broad classification of tumors into tumor site and histopathology. Several lines of evidence have shown that a molecular approach to patient selection may be better in its capacity to improve patient outcomes. CUSTOM is an innovative clinical trial that allows for the parallel evaluation of multiple targeted therapies in molecularly selected patients with multiple cancer histological subtypes and the prospective evaluation of multiple molecular biomarkers. Methods: All patients with advanced lung cancer and thymic malignancies and a good performance status are eligible independently of previous lines of treatment. The trial begins with tumor biopsy and molecular profiling using a multi-platform approach to identify oncogenic alterations in more than 34 genes for treatment allocation (12 genes) and exploratory purposes. Depending upon the specific biomarker identified, patients are then triaged into 5 experimental arms. Erlotinib for sensitizing EGFR mutations; AZD6244 for KRAS, NRAS, HRAS and BRAF mutations; MK2206 for PIK3CA, AKT and PTEN mutations and PIK3CA amplification; Lapatinib for ERBB2 mutations or amplification; Sunitnib for KIT mutations and PDGFRA mutations and amplification. Patients not eligible for the experimental treatment arms are enrolled into a standard treatment arm. Upon disease progression patients are eligible for repeat biopsy and molecular profiling in order to identify molecular changes and mechanisms of resistance. All patients are followed until death. The primary endpoint is response rate and secondary endpoints include progression-free survival, duration of response and overall survival. With three disease types and five experimental drugs, there are 15 possible treatment arms which will be under active consideration. For each of these, the study will be conducted as an optimal two-stage phase II trial in order to rule out an unacceptably low 10% clinical response rate in favor of a modestly high response rate of 40%. As of January 11, 2012, two hundred and sixteen patients have been enrolled.
CA184-104: Randomized, multicenter, double-blind, phase III trial comparing the efficacy of ipilimumab (Ipi) with paclitaxel/carboplatin (PC) versus placebo with PC in patients (pts) with stage IV/recurrent non-small cell lung cancer (NSCLC) of squamous histology.
Authors: Reck Martin , Lu Haolan , Gribkoff Greta , Maier Sabine , McGovern Rachel , Cuillerot Jean-Marie , Lynch Thomas James 
Published: March 2020

TPS7611 Background: Years of research in advanced NSCLC have not improved outcomes for the squamous subtype beyond those of standard platinum doublets. Evidence of responses to immune therapies in NSCLC of squamous cell histology supports investigation in this subtype. Ipi, a fully human monoclonal antibody which blocks CTLA-4, augments antitumor immune responses. Ipi improved overall survival (OS) in advanced melanoma, with side effects managed using product-specific treatment guidelines; immune-related response criteria (irRC) were derived from WHO criteria to better capture response patterns observed with Ipi. A randomized Phase 2 study of Ipi/PC in Stage IV NSCLC pts showed significant improvement in progression-free survival (PFS), as measured by mWHO or irRC, with a trend toward improved OS, over chemotherapy alone in pts receiving phased Ipi/PC (Ipi started after 2 cycles of PC). Phased Ipi/PC appeared to show efficacy in tumors of squamous histology. Addition of Ipi did not exacerbate PC toxicity, and immune-related adverse events were managed using protocol-specific guidelines. A Phase 3 trial (ClinicalTrials.gov identifier NCT01285609) is examining whether phased Ipi/PC will prolong OS in chemotherapy-naïve pts with squamous NSCLC. Methods: Stage IV/recurrent squamous NSCLC with ECOG 0-1 will be included; pts with CNS metastases or history of autoimmune disease will be excluded. Pts are randomized to receive 2 cycles of PC (175 mg/m2 and AUC=6, respectively; IV), followed by 4 cycles of study drug (Ipi in Arm A, placebo in Arm B; IV) with 4 additional cycles of PC (total 6 cycles). Pts without progressive disease (PD) after induction receive maintenance therapy with blinded study drug Q12W until PD per mWHO. The study will randomize 920 pts 1:1 between arms. The primary endpoint of this study is OS; secondary endpoints include OS among pts who receive blinded therapy, PFS and best overall response rate.
Phase III study of investigational MLN8237 (alisertib) versus investigator’s choice in patients (pts) with relapsed/refractory (rel/ref) peripheral T-cell lymphoma (PTCL).
Authors: O'Connor Owen , Leonard E. Jane , Benaim Ely 
Published: March 2020

TPS8110 Background: PTCL is a rare form of aggressive non-Hodgkin lymphoma (NHL), accounting for 5–20% of NHL diagnoses. Standard NHL therapies developed primarily for B-cell lymphomas are not optimal for PTCL and early relapse is common. Current treatments for rel/ref PTCL include pralatrexate, romidepsin, and gemcitabine; however, outcomes remain poor. The oral, investigational drug, MLN8237, is a selective inhibitor of Aurora A kinase (AAK) – a key mitotic regulator that is overexpressed or amplified in various human tumors. Emerging clinical data from a phase II study of single agent MLN8237 in rel/ref aggressive T-cell lymphoma (Friedberg et al, ASH 2011) support further clinical evaluation in this indication. Methods: In this open-label, randomized, phase III study, a maximum of 354 adults with rel/ref PTCL after ≥1 prior systemic cytotoxic therapies will be enrolled at approximately 140 centers worldwide. Pts will be randomized 1:1 to MLN8237 50 mg twice daily as an enteric coated tablet on days 1–7 of 21-day cycles, or to investigator’s choice of: pralatrexate 30 mg/m2 IV once weekly for 6 weeks in 7-week cycles; romidepsin 14 mg/m2 IV on days 1, 8, and 15 of 28-day cycles; or gemcitabine 1000 mg/m2 IV on days 1, 8, and 15 of 28-day cycles. Pts with disease response/stabilization will be able to continue treatment provided that clinical benefit is demonstrated and treatment is tolerable. The expected study duration is 44 months. Primary endpoints are overall response rate (complete response [CR] + partial response) and progression free survival by International Working Group criteria (Cheson et al, 2007). Secondary endpoints include CR rate, overall survival, time to progression, time to response, duration of response, safety, and quality of life. Exploratory endpoints include an evaluation of candidate biomarkers (such as AAK protein expression levels and gene amplification, and the tumor proliferative marker Ki-67) in tumor biopsies. This study is registered at ClinicalTrials.gov: #NCT01482962.
Pilot evaluation of sulforaphane in melanoma patients with multiple atypical nevi: Tissue STAT1 and STAT3 as risk markers.
Authors: Lobur David , Davar Diwakar , Singh Shivendra , Beumer Jan Hendrik , Edington Howard , Tarhini Ahmad A. , Tawbi Hussein , Zarour Hassane M. , Talalay Paul , Kirkwood John M. 
Published: March 2020

TPS8606 Background: Increasing incidence and the poor prognosis of advanced melanoma argue for prevention efforts. Primary prevention and ultraviolet radiation (UVR) reduction have failed to gain traction in the population, making chemoprevention increasingly attractive. Sulforaphanes (SFN) are bioactive cruciferous compounds rich in the Brassica family, especially broccoli sprouts. Topical broccoli sprout extracts (BSE) decrease UVR erythema response in human skin, and may protect against UVR DNA damage. We have shown SFN inhibition of STAT3, which is constitutively activated in melanoma. We have therefore initiated a pilot study to evaluate BSE SFN in relation to melanoma progression biomarkers, and expression of STAT proteins of atypical melanocytic nevi. Methods: Melanoma patients with >2 atypical nevi are eligible for this trial, which aims to define the safety and clinico-pathological response to oral BSE-SFN. Secondary objectives are documentation of pharmacokinetics and pharmacodynamics of BSE-SFN, and the modulation of STAT 1/3 expression in atypical nevi and normal skin. Baseline photo-documentation and atypical nevus biopsy is performed to assess histopathological atypia and STAT 1/3 expression. Adjacent normal skin biopsies will establish baseline skin SFN levels. Six subjects per group will be accrued at daily dosages of 50, 100, and 200 μM. Subjects must abstain from dietary glucosinolates and isothiocyanates for the study duration and maintain food diaries. Following 27 days of BSE-SFN, blood samples, photography of index atypical nevi, and biopsies of selected atypical nevi and normal skin will be obtained. The three dosage groups will be analyzed for changes in atypia, SFN localization histopathology, and STAT 1/3 expression in the nevi and skin harvested at baseline and at study completion. This trial, UPCI 10-114, has received an IND and is IRB-approved. Accrual is planned to be completed during 2012-13.
CATCH: A randomized trial comparing tinzaparin versus warfarin for treatment of acute venous thromboembolism (VTE) in cancer patients.
Authors: Lee Agnes Y. , Bauersachs Rupert , Janas Mette S. , Jarner Mikala F. , Kamphuisen Pieter W , Meyer Guy , Paz-Ares Luis , Khorana Alok A. ,   on behalf of the CATCH Investigators
Published: March 2020

TPS9149^ Background: VTE is a major cause of morbidity and mortality in cancer patients. LMWHs have been shown to be superior to warfarin in one randomized study, but adequately powered confirmatory studies have not been conducted and warfarin continues to be widely used for treatment of cancer-associated VTE. Methods: We are conducting an open-label, randomized trial of tinzaparin versus warfarin in 900 patients with active cancer and symptomatic proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Tinzaparin is given at full treatment doses (175 IU/kg once daily) for 6 months in the experimental arm and initial tinzaparin treatment for 5-10 days followed by dose-adjusted warfarin (target INR 2.0-3.0) is given for 6 months in the control arm. The primary composite outcome is time to recurrent VTE event, including incidentally diagnosed VTE and fatal PE. Baseline characteristics will be analysed for their ability to predict the risk for recurrent VTE or bleeding. In particular, the parameters of the Khorana scale and Wells rule will be tested for their usefulness in predicting recurrent VTE. Predictive biomarkers will be tested including D-dimer and Tissue Factor. Assessment of post-thrombotic syndrome (PTS), quality of life and healthcare resource utilization will also be performed. The trial is recruiting in > 160 sites in >25 countries in 4 continents (NCT01130025). As of Jan 2012, 135 sites were activated for study enrolment and 228 patients have been enrolled. We anticipate completion of enrolment in Jan 2013. The results obtained from this study will add significantly to the knowledge on the efficacy, safety and cost-effectiveness of LMWH to prevent recurrent VTE. Important prospective data on the clinical significance of incidental VTE in patients with active cancer will be generated, and analyses of risk stratification parameters will add important information that may help to further tailor therapy. The study of PTS, which has not previously been done in this selected patient population, will add to the evidence that tinzaparin significantly reduces the incidence of PTS and leg ulcers (Hull et al, Am J Med 2009;122:762-9).
Randomized phase III trial to evaluate radiopharmaceuticals and zoledronic acid in the palliation of osteoblastic metastases from lung, breast, and prostate cancer: Report of RTOG 0517.
Authors: Seider Michael J. , Shook Stephanie , Langer Corey J. , Wyatt Gwen , Demas William F. , Rashtian Afshin , Clausen Cathy L , Derdel Jerry , Cleary Sean F , Peters Christopher A. , Ramalingam Ashok , Clarkson James E. , Tomblyn Michael B. , Rabinovitch Rachel , Kachnic Lisa A. , Berk Lawrence B. ,   RTOG
Published: March 2020

TPS9150 Background: Skeletal related events (SREs) diminish quality of life (QOL) as well as overall survival (OS) in patients with bone metastases, a common event in breast, lung and prostate cancer. SREs can be reduced or delayed by the use of bisphosphonates. It is postulated that the radiopharmaceuticals, Strontium-89 (Sr89) and Samarium-153 (Sm153), when added to a bisphosphonate can decrease the incidence of SREs. Methods: RTOG 0517 randomized patients with breast, lung and prostate cancer and blastic bone metastases to either Zoledronic acid (ZA) alone or ZA plus a single standard dose of either Sr89 or Sm153. No limitations were placed on additional therapy such as chemotherapy or hormonal treatment. The projected median time to SRE [pathological bone fracture, spinal cord compression, surgery to bone, or radiation to bone] for the ZA arm was 10.4 months requiring 257 SRE events to detect a 33% relative reduction for the radiopharmaceutical arm in the time to development of an SRE with 90% power. Other study objectives included quality of life, pain control, OS and toxicity. Results: 261 patients (median age 68; 62% male; 55% prostate, 35% breast, 10% lung) were accrued from July 2006 through February 2011 (4.6 patients/month). Due to a lower than expected rate of SREs in the control (ZA) arm, the study was closed early and therefore did not reach the targeted accrual. 28 (17.4%) patients in the ZA arm and 27 (16.8%) in the radiopharmaceutical arm experienced an SRE. Median time to development of an SRE in the ZA and radiopharmaceutical arms was 11.60 and 16.74 months, respectively (p=.47). Median OS in the ZA arm and radiopharmaceutical arm was 15.95 and 11.18 months, respectively (p=0.12). Cox proportional hazards regression model showed that baseline characteristics, including gender, race, ethnicity, primary disease site or number of bone metastases, had no significant impact on OS. There was no difference in QOL parameters or toxicities between the two arms. Conclusion: Patients receiving ZA only experienced a much lower SRE rate than was hypothesized. The addition of Sr89 or Sm153 did not result in a difference in SREs, OS, or QOL
A multi-site, fixed dose, parallel arm, double-blind, placebo controlled, block randomised trial of the addition of infusional octreotide or placebo to regular ranitidine and dexamethasone for the evaluation of vomiting associated with bowel obstruction at the end of life.
Authors: Currow David C , Clark Katherine , Cartmill John , Pather Selvin , Plummer John , Eckermann Simon , Abernethy Amy Pickar , Agar Meera , Quinn Stephen 
Published: March 2020

TPS9153 Background: Bowel obstruction due to advanced cancer that is surgically inoperable is a major management problem. Studies to date have either been underpowered or have used comparators that may not draw on the best available evidence. Methods: This double-blind, block randomised, placebo controlled, set dose, parallel arm study was conducted across 12 sites in Australia. Eligibility included inoperable bowel obstruction secondary to cancer or its treatments. The intervention was the addition of infusional octreotide or placebo in addition to 200mg ranitidine per 24 hours parenterally and 4mg per 24 hours parenterally of dexamethasone. The primary outcome measure was the numbers of days free of vomiting up to 72 hours after all medications were administered the first time. Participants were also administered between 10-20mls per hour of subcutaneous isotonic fluid over the 72 hour period. Results: This study will close to recruitment in March 2012. To date 89 of 92 required participants have been randomised. Conclusions: This adequately powered study will define the additional net clinical benefit derived from octreotide over placebo in people who have an anti-secretary agent (ranitidine) and glucocorticoids (dexamethasone).
Intraperitoneal radioimmunotherapy (RIT) for desmoplastic small round cell tumor (DSRCT).
Authors: Modak Shakeel , Carrasquillo Jorge A. , La Quaglia Michael P. , Zanzonico Pat , Pandit-Taskar Neeta , Lewis Jason S. , Cheung Nai-Kong V. 
Published: March 2020

TPS9595 Background: DSRCT, a rare sarcoma of adolescents and young adults arises from serosal surfaces typically the peritoneum. It is characterized by t(11;22)(p13;q12) chromosomal translocation; and is lethal in >80% of patients despite aggressive surgery and chemoradiotherapy. Disease recurrence often presents as multifocal peritoneal implants, making it uniquely suited for intraperitoneal (IP) targeting. Since DSRCT is radiosensitive, we hypothesize that improving local control with targeted radiotherapy may reduce relapse and enhance survival. IP RIT, by virtue of prolonged residence time, and slow/incomplete transfer to the circulation, may selectively target IP disease while minimizing organ toxicity. The anti-4Ig-B7H3 murine monoclonal antibody 8H9 binds to 96% of primary DSRCT with restricted reactivity to normal tissue (Med Pediatr Oncol 39:547). 131I-8H9 targets DSRCT xenografts and has proven safe at 80mCi when injected intrathecally (J Neurooncol 97:409). 124I-8H9, a novel positron-emitting radioimmunoconjugate is ideally suited for quantitative imaging and pharmacokinetic (PK) studies. Methods: We have initiated a phase I study to test the safety of IP RIT using 131I-8H9 in patients with DSRCT (clinicaltrials.gov NCT01099644). Cohorts of 3-6 patients are treated with 131I-8H9 at escalated doses from 30mCi/m2-60mCi/m2 as a single IP injection. An IP tracer dose of 2mCi124I-8H9 is given prior to 131I-8H9 to acquire high-resolution PET images and data on 8H9 tumor targeting and biodistribution. PK is also studied using serial blood draws. Patients are monitored for toxicity clinically and biochemically. Response to treatment is assessed using RECIST criteria and via a follow up 124I-8H9 PET scan if tumor targeting is noted on initial imaging. Hematopoietic stem cells are harvested a priori to reverse myelosuppression if any. Three cohorts of patients (n=9) up to 50mCi/m2 have completed therapy thus far without dose-limiting toxicity or myelosuppression. This is the first study of IP RIT in pediatrics, and the first to use PET for IP RIT. Data obtained will be critical in establishing safety of IP 131I-8H9 in children and young adults, and in designing phase II trials to study efficacy of IP RIT for DSRCT.
10-yr follow-up results of NSABP B-32, a randomized phase III clinical trial to compare sentinel node resection (SNR) to conventional axillary dissection (AD) in clinically node-negative breast cancer patients.
Authors: Julian Thomas B. , Anderson Stewart J. , Krag David N. , Harlow Seth P. , Costantino Joseph P. , Ashikaga Takamaru , Weaver Donald L. , Mamounas Eleftherios P. , Wolmark Norman 
Published: March 2020

1000 Background: NSABP B-32, the largest surgical prospective randomized phase III trial was designed to compare overall survival (OS), disease-free survival (DFS), and morbidity between SNR alone vs SNR + AD in SN negative (-) pts. We present 10 yr outcome data for primary endpoints as well as updated data on the effect of occult metastases, found later in the SN by central, detailed pathologic analysis. Methods: 5,611 women with operable, clinically N0, invasive breast cancer were randomized to SNR + AD (Group [Grp] 1) or to SNR alone with AD only if SNs were positive (Grp2). 3,989 (71.1%) of 5,611 pts were SN-. 3,986 (99.9%) of these SN- pts had follow-up information: Grp 1: 1,975, Grp 2:2,011. Median time on study was 9.4 yrs. Cox proportional hazard models adjusting for study stratification variables were used to compare OS and DFS between the two groups. Two-sided p values were used. HR values > 1 indicate a more favorable outcome in Grp 1 Results: At 10 yrs, there continues to be no significant difference in OS between the two groups (HR: 1.11, p = 0.27). 10 yr Kaplan-Meier (K-M) estimates for OS are 87.8% for SNR alone and 88.9% for SNR + AD. There continues to be no significant difference in DFS between the two groups (HR: 1.01, p=0.92). 10-yr K-M estimates for DFS were 76.9% for both groups. Occult nodal disease was originally detected in 3,884 pts (15.8%) with SN- on initial H and E analysis. Comparisons between the groups with and without occult disease yielded an adjusted HR for OS: 1.25 (p = 0.08) with an absolute difference at 10 yrs of 2.8% and a HR for DFS: 1.24 (p = 0.018) with an absolute difference of 4.1%. The cumulative incidences of local-regional events were low (10-yr values: SNR 4.0%, SNR+AD, 4.3%) and not significant (HR: 0.95, p = 0.77). Conclusions: At 10 yrs there continues to be no significant differences in OS and DFS between SNR and SNR + AD in pts with negative SN. The relative increase in risk of DFS and OS for pts with occult SN metastases remains stable. Support: PHS grants: NSABP: U10CA-12027, U10CA-37377, U10CA-69651, U10CA-69974; VT Ca Cntr: P30 CA22435; DNK: 5RO1CA074137 NCI Dpt HHS. Clinical trial information: NCT00003830.