bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized multicenter phase III study comparing weekly versus every 3 week carboplatin (C) plus paclitaxel (P) in patients with advanced ovarian cancer (AOC): Multicentre Italian Trials in Ovarian Cancer (MITO-7)– European Network of Gynaecological Oncological Trial Groups (ENGOT-ov-10)–Gynecologic Cancer Intergroup (GCIG ) trial.
Authors: Pignata Sandro , Scambia Giovanni , Lauria Rossella , Raspagliesi Francesco , Benedetti Panici Pierluigi , Cormio Gennaro , Katsaros Dionyssios , Sorio Roberto , Cavazzini Giovanna , Ferrandina Gabriella , Breda Enrico , Murgia Viviana , Sacco Cosimo , Asensio Sierra Nuria Maria , Pisano Carmela , Salutari Vanda , Weber Beatrice E. , Pujade-Lauraine Eric , Gallo Ciro , Perrone Francesco 
Published: March 2020

LBA5501 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Saturday, June 1, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
An adaptive randomized phase II trial to determine pathologic complete response with the addition of carboplatin with and without ABT-888 to standard chemotherapy in the neoadjuvant treatment of triple-negative breast cancer.
Authors: Avery Tiffany P. , Berger Adam C. , Kovatich Albert J. , Rui Hallgeir , Hyslop Terry , Mitchell Edith P. 
Published: March 2020

TPS1135 Background: Inhibition of poly (ADP-ribose) polymerase (Parp) is a potential targeted therapy for triple-negative breast cancer (TNBC). Clinical trials of Parp inhibitors in metastatic TNBC have shown conflicting results. Issues regarding the use of Parp inhibitors in TNBC include choosing a selective Parp inhibitor and selecting an appropriate chemotherapy backbone. The current trial addresses these questions by combining a validated Parp inhbitor, ABT-888, with carboplatin and paclitaxel. Platinum agents have shown synergy with Parp inhibitors in preclinical models and efficacy in clinical trials. The combination of paclitaxel and carboplatin with Parp inhibitors has shown efficacy in phase I trials. Methods: This is a phase II, two-arm neoadjuvant trial of women with TNBC. Eighty patients will be enrolled. Randomization will follow a 1:1 allocation initially, then will follow a Bayesian adaptive allocation in which each prior response will be evaluated and patients assigned preferentially to the better responding arm. The primary endpoint is pathologic complete response (pCR). Secondary endpoints include correlation of pCR with biomarkers, imaging, and circulating tumor cells (CTCs). Treatment: Arm 1: Paclitaxel 80 mg/m2 + carboplatin AUC=2 (12 weekly cycles) + filgrastim followed by doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 (4 cycles every 3 weeks) + pegfilgrastim. Arm 2: ABT-888 (150mg PO bid) + paclitaxel 80 mg/ m2 + carboplatin AUC=2 (12 weekly cycles) + (filgrastim) followed by doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 (4 cycles every 3 weeks) + (pegfilgrastim). Eligibility: Women ≥ 18 years old with clinical stage IIB or stage IIIA, IIIB, or IIIC untreated TNBC (ER <1% , PR <1% , Her-2/neu 0, 1+ on IHC or 2+ and FISH ratio < 1.8) are eligible. Correlative Studies: Correlation of pCR with tissue expression of CK5, EGFR, ERCC1, Ki-67, Parp1, and longitudinal enumeration of CTCs will be done. Exploratory tissue biomarkers with prognostic and predictive value will be correlated with pCR. Enrollment: The trial will begin accrual in February 2013.
Phase II study of eribulin mesylate as first- or second-line therapy for metastatic HER2-negative breast cancer.
Authors: Iwamoto Mitsuhiko , Sato Nayuko , Terasawa Risa , Fujioka Hiroya , Takahashi Yuko , Kimura Kosei , Tanaka Satoru , Uchiyama Kazuhisa 
Published: March 2020

TPS1140 Background: Eribulin mesylate is a nontaxane microtubule dynamics inhibitor that is approved in patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens (including an anthracycline and a taxane) for metastatic breast cancer. In a previous phase III study, eribulin mesylate demonstrated to significant improvement in overall survival in patients with heavily pretreated, locally recurrent or metastatic breast cancer when compared to treatment of physician’s choice. The majority of patients were HER2-negative and all had previously failed 2 or more regimens. Overall, the tolerability and positive phase III findings in this patient population suggest eribulin mesylate may provide a treatment advantage when given earlier in the course of therapy for HER2-negative, metastatic breast cancer. Methods: This study is phase II, multicenter, open-label, single-arm in patients with HER2-negative metastatic breast cancer who have been treated with chemotherapeutic regimens including an antheracycline and a taxane. Eribulin mesylate (1.4mg/m2) will be given on days 1 and 8 of each 21-day cycle. The primary endpoint is objective response rate, and secondary endpoints include duration of response, progression-free survival, overall survival, the safety of the treatment, and quality of life. Eligibility Criteria: Patients must have confirmed HER2-negative metastatic breast cancer with at least 4 weeks since prior neoadjuvant or adjuvant chemotherapy, and have not received over 2 chemotherapeutic regimens for metastatic disease. Additional eligibility criteria include adequate performance status (ECOG PS:0-2) and end organ/marrow function, and ejection fraction > 50%. Accrual: This study began in December 2012. The expected end of accrual of 35 patients will be the last quarter 2015.
Randomized controlled phase II trial of simvastatin as prophylaxis against radiation-induced skin toxicity in breast cancer patients.
Authors: Joseph Shibu , Round Glenys , Jameson Michael B. , Boyd Jenny May , Ragupathy Rajan 
Published: March 2020

TPS1143 Background: Most women receiving adjuvant radiation (RT) for breast cancer (BC) have significant acute skin toxicities ranging from erythema to moist desquamation. Late skin toxicities include fibrosis and telangiectasia. The inflammatory response to RT is mediated by RT-induced endothelial cell expression of the cell adhesion molecule E-selectin, to which neutrophils and monocytes adhere and then infiltrate into tissues. Blockade of this mechanism could interrupt the inflammatory cascade at an early stage. Preclinical studies have shown that statins can inhibit RT-induced E-selectin expression and skin and intestinal inflammation in vivo without impairing DNA damage or tumour response to RT. Retrospective clinical studies have shown reduced relapse rates with statins in breast cancer patients. Thus statins have the potential to reduce the acute RT-induced inflammatory component without compromising the DNA-damaging effects essential to cancer cell death. This is the only registered trial evaluating the effects of statins on acute RT toxicity. Methods: Randomised open controlled phase II trial of simvastatin 40mg daily during and for 3 weeks after RT. Eligibility: women with invasive or in-situ BC receiving whole-breast +/- lymphatic RT; dose fractionation schedules include 50Gy/25 #, 45Gy/20#, 42.5Gy/16 # or 40Gy/15#, with or without a boost; may have had prior chemotherapy, and be on hormonal or Trastuzumab therapy during RT; no prior statins within 6 weeks of starting RT. Stratification by breast conserving surgery vs mastectomy, use of boost and fraction size (<2 Gy vs >2 Gy). Primary endpoint: incidence of > grade 2 acute RT-related skin toxicity. Secondary endpoints: time to onset of skin toxicity, proportion requiring additional topical treatment, compliance with trial medication, statin-related toxicities and subjective RT-related toxicities (breast discomfort and fatigue). Statistical design: 130 randomised patients gives 90% power (one-sided a 0.20) to detect a reduction in > grade 2 acute skin toxicity from 55% to 35%. Enrolment opened January 2013, planned to complete by April 2014. Clinical trial information: ACTRN12612000662864.
SHAVE: A randomized controlled trial of routine shave margins versus standard partial mastectomy.
Authors: Chagpar Anees B. , Stavris Karen , Killelea Brigid K. , Tsangaris Theodore , Horowitz Nina Ruth 
Published: March 2020

TPS1145 Background: It is well known that partial mastectomy for breast cancer is associated with a positive margin rate of 20-40% in most series. This has led some surgeons to advocate for routine cavity shave margins as a means of reducing re-excision rates. Others, however, feel that such a practice may be unwarranted and question the volume of tissue removed, cosmetic outcome and increase in operative time. It is unclear which of these two approaches is optimal; therefore, a prospective randomized controlled trial was proposed. Methods: Given the primary endpoint of positive margin rates (defined as a margin of < 1mm), the study was powered to find a difference between 30% in the standard partial mastectomy group and 15% in the routine shave margin group. To reach a power of 80% with alpha of 5%, 122 patients were required in each arm; we therefore set N=250 with a 1:1 randomization scheme. Patients are evaluated preoperatively and all patients undergoing a partial mastectomy for stage 0-III breast cancer are eligible; including those who have completed neoadjuvant chemotherapy. Patients are stratified according to stage and randomized within strata. After informed consent, patients undergo a standard partial mastectomy (including specimen radiography as needed). Surgeons may resect additional tissue at that time according to their standard practice. At the completion of this procedure, the randomization envelope is opened in the operating room and surgeons are instructed to either shave (ie., take additional circumferential margins) or close (no shave). Patients will be followed for five years. Outcome measures include: positive margin/re-excision rate, local recurrence, volume of tissue resected, cosmetic outcome, and intraoperative time. To date, over 130 patients have accrued to this trial. Initial results are expected to be reported in 2014. Clinicaltrials.gov identifier: NCT01452399
Investigating hereditary risk from T790M (inherit): A prospective multicentered study of risk associated with germ-line EGFR T790M.
Authors: Oxnard Geoffrey R. , Heng Jennifer C. , Rainville Irene R. , Dahlberg Suzanne Eleanor , Sable-Hunt Alicia L. , Wiesner Georgia L. , Taylor Kelly A. , Jackman David Michael , Janne Pasi A. , Garber Judy Ellen 
Published: March 2020

TPS1606 Background: The EGFR T790M mutation, commonly associated with acquired resistance to EGFR kinase inhibitors, has also been seen as a germline mutation in association with familial lung cancer. In collaboration with the Addario Lung Cancer Medical Institute (www.ALCMI.net), we initiated a prospective trial to identify patients and families carrying germline EGFR mutations in order to characterize their cancer risk. Preliminary data: In a prior study (Oxnard et al, JTO, 2012), it was found that patients with lung cancers found to harbor EGFRT790M at diagnosis have a 50% chance of carrying an underlying germline T790M mutation. This suggests that study of patients known to carry T790M in their cancer will enrich for a germline event that otherwise is too rare to study prospectively. Subject eligibility: Three cohorts are eligible: (1) Patients with a cancer (lung or other) harboring EGFR T790M on tumor genotyping; lung cancers that acquire EGFR T790M only after treatment are ineligible. (2) First-degree relatives of patients carrying a germline EGFR mutation. (3) Patients already known to carry a germline EGFRmutation on prior testing. Subjects are referred to cohort 1 based upon routine genotyping results from commercial laboratories (e.g. Response Genetics Inc., Los Angeles, CA). Methods: Subjects may present at a participating cancer center or may participate remotely through a study website (www.Dana-Farber.org/T790Mstudy). Eligible patients submit a saliva and/or blood specimen for central testing in a CLIA lab. After counseling, patients carrying germline EGFR mutations have the option of inviting first-degree relatives to participate. Genetic counseling is coordinated at the participating center or offered over the phone. Chest CT scans are collected from germline carriers and analyzed centrally to study nodule characteristics. Patients are clinically followed for 2 years. At time of submission, 6 subjects have enrolled from 3 different families and 4 different US states. (NCT01754025) Funding: Supported by grants from the Conquer Cancer Foundation of ASCO and the Bonnie J. Addario Lung Cancer Foundation. Clinical trial information: NCT01754025.
Evaluation of whole body MRI for early detection of cancers in subjects with germ-line TP53 mutation (Li-Fraumeni syndrome).
Authors: Caron Olivier , Frébourg Thierry , Bourbouloux Emmanuelle , Bonadona Valérie , Mari Véronique , Maugard Christine , Eisinger François , Barouk-Simonet Emmanuelle , Gauthier-Villars Marion , Tinat Julie , Nogues Catherine , Dugast Catherine , Canale Sandra , Guillemeau Claire , Benusiglio Patrick R. , Brugieres Laurence ,   French LFS Working Group
Published: March 2020

TPS1607 Background: The TP53 germline mutation carriers have a huge increase of cancer risk. The cancer spectrum is particularly broad (breast, sarcoma, brain tumour, leukaemia, …). The clinical management of these people is challenging, mainly concerning sarcoma screening. Moreover, some data let speculate that normal cells of these carriers are particular hypersensitive to X-rays. Among major breakthroughs in radiology, whole-body MRI (WBMRI) may contribute to TP53 carriers surveillance. In order to update the french guidelines on Li-Fraumeni families management, the LIFSCREEN study ( NCT01464086 ) was designed to assess its usefulness in France. Methods: This open, randomized, multicentric trial will evaluate the efficacy and tolerability of two screening schemes, avoiding irradiating exams. In the standard arm, people undergo clinical exam, abdominal sonography, brain MRI, Complete Blood Count, breast MRI, breast sonography, depending on the age) at inclusion, Month 12, Month 24, and a study visit at Month 36. In the experimental arm, people included undergo the same scheme, completed by a diffusion WBMRI at M0, M12, M24. At each round, quality of life and psychological impact will be assessed by self-questionnaires and semi-structured qualitative interviews. In an ancillary study, serums will be collected at each step. Subjects meeting these criteria are eligible: any TP53 germline mutation carrier, with or without personal cancer history, aged >5 and <71. A hundred people will be enrolled and randomized. The primary objective is to assess the efficiency of each scheme, evaluated by the cancer incidence at 3 years. Notably, sensitivity and specificity of each exam will be studied. As a secondary objective, the acceptability of each scheme will be assessed by quality of life / psychological questionnaires interpretation (SF-36, HADS, TAS 20, CBCL, CDI, R-CMAS, depending on subject’s age). Recruitment began in December, 2011. To date, 32 patients have been enrolled on 8 french study sites. The study will soon be implemented in another 12 sites. This academic study is, to our knowledge, the first randomized trial on this topic, and supported by the french “Ligue contre le cancer.” Clinical trial information: NCT01464086.
Change in mammographic density with metformin use: A companion study to NCIC study MA.32.
Authors: Wood Marie E. , Qin Rui , Le-Petross Huong T. , Hwang E Shelley , Ligibel Jennifer A. , Mayer Ingrid A. , Marshall James Roger , Goodwin Pamela Jean 
Published: March 2020

TPS1608 Background: Metformin may have growth inhibitory effects on many cancer types including breast cancer. NCIC MA.32 is a randomized placebo-controlled trial examining the effects of 5 years of metformin in women with breast cancer ( http://clinicaltrials.gov/show/NCT01101438 ). This trial offers us the opportunity to explore the effects of metformin on breast cancer biomarkers to gain an understanding of the potential chemo preventive effects of this drug. The primary aim of this companion to MA.32 (Alliance trial # A211201) is to examine the effects of 1 year of metformin vs placebo on breast density for women with Estrogen Receptor negative (ER-) breast cancer. Secondary aims of this study include: evaluation of breast density following 2 years of metformin use, and correlation of density with fasting insulin, glucose and Homeostasis Model Assessment (HOMA). Exploratory aims include examination of the effects of metformin on second cancer rates. Methods: Eligible women must have been enrolled on MA.32 (North America accrual completed January 23, 2013), have hormone receptor-negative breast cancer, and breast composition on mammography >25% glandular density, have a digital mammogram within 12 months of registration on MA.32 and have an intact, unaffected contralateral breast. Women enrolled on this study must provide menstrual cycle data (if premenopausal) and digital mammograms. All other study related information is gathered through participation in MA.32. Mammographic density will be calculated using Cumulus software (the Boyd method). Our accrual goal is 458 patients (229 per arm) and with an assumption of 20% drop out due to drug intolerance and another 20% due to ineligibility. Therefore, with a sample size of 274 (137 per arm) we will have at least 85% power to detect a 4% difference between study arms, i.e., 5% change from baseline to one year of treatment for metformin vs. 1% for placebo, using the two-sided two-sample t-test at a significance level of 5%. This study was activated in the United States on 8/22/2012 and 15 patients have been accrued to date. This study is sponsored by the NCI and the Alliance for clinical trials. Clinical trial information: NCT01666171.
Sequential therapy with the selective T-type calcium channel blocker mibefradil and temozolomide in patients with recurrent high-grade gliomas: An Adult Brain Tumor Consortium phase I study (ABTC1101).
Authors: Holdhoff Matthias , Grossman Stuart A. , Supko Jeffrey G. , Ye Xiaobu , Fisher Joy D. , Desideri Serena , Wahl Richard L. , Schiff David 
Published: March 2020

TPS2105 Background: Despite recent advances in their treatment, high-grade gliomas (HGG) carry a dismal prognosis. Treatment options at recurrence are particularly limited and a re-challenge with temozolomide (TMZ) frequently appears as the most appropriate systemic treatment option in patients whose progression occurred off TMZ. This study investigates the sequential treatment of mibefradil (MIB), a selective Cav3 calcium channel blocker, and standard dose TMZ. Preclinical data showed that Cav3 inhibitors such as MIB can slow tumor growth without significant effect on normal tissues and can induce cell cycle arrest in cancer cells at the G1/S-phase checkpoint. We hypothesize that withdrawal of MIB could synchronize and release cells into S-phase, thereby potentiating the cytotoxic effect of TMZ. Methods: This trial is an open-label, multicenter phase I study, structured into a dose escalation phase to determine the maximum tolerated dose of MIB (MTD; Primary Objective) and an expansion cohort of 10 patients at the MTD level. Adults with recurrent HGG (WHO grade 3 or 4) who have previously received standard adjuvant therapy with radiation (RT) and TMZ (last dose ≥ 3 months prior to enrollment) and who have not received other cytotoxic therapy (except for carmustine wafers) are eligible. Patients receive oral MIB for 7 days on a 4 x/day (QID) schedule, followed by standard dose TMZ at 150-200 mg/m2 for 5 days each 28-day cycle. Dose finding uses a modified 3+3 design, starting at MIB 25 mg po QID (100 mg/day) with dose increases of 25 mg/dose per dose level. The target dose-limiting toxicity (DLT) rate is ≤ 33%. Secondary Objectives: (1) safety and adverse event analysis (incl. cardiac monitoring during cycle 1), (2) pharmacokinetic profile of MIB, (3) response assessment (RANO criteria), and (4) assessment of the potential effect of MIB on tumor DNA synthesis as determined by fluorothymidine positron emission tomography (FLT PET; extension cohort). Enrollment status as of January 2013: cohort 1 completed without DLT; cohort 2 enrolling at MIB 200 mg/day. Clinical trial information: NCT01480050.
Phase I lead-in to a 2x2x2 factorial trial of dose-dense temozolomide, memantine, mefloquine, and metformin as postradiation adjuvant therapy of glioblastoma (GBM).
Authors: Penas-Prado Marta , Groves Morris D. , Mammoser Aaron G. , Melguizo Isaac , De Groot John Frederick , Conrad Charles A. , Tremont-Lukats Ivo , Loghin Monica Elena , Puduvalli Vinay K. , Sulman Erik P. , Hess Kenneth R. , Aldape Kenneth D. , Gilbert Mark R. , Yung W. K. Alfred 
Published: March 2020

TPS2106 Background: Treatment for GBM is an area of unmet need. Despite optimal therapy, survival is poor and 2nd line therapies are scarce. There is an urgent need to find better treatments for recurrence, but also more effective 1st line therapies. Dose-dense temozolomide (ddTMZ) using the 7/14-day regimen has shown promising preliminary results in combination with cytostatic agents. Memantine (MEM) is a glutamate receptor (NMDA) blocker with antiproliferation properties and possibly neuroprotective effect. Mefloquine (MFQ) induces autophagy and apoptosis. Metformin (MFM) has mTOR inhibitor properties. Methods: Trial Design: Phase I/II trial to evaluate adjuvant ddTMZ with MEM MFQ and MFM. Primary objective Phase I: MTDs of ddTMZ with MEM/MFQ/MFM, 3+3 design. MTDs will be the recommended Phase II doses for a subsequent randomized factorial Phase II trial (ddTMZ alone and single, double and triple combinations). Accrual of about 55 eligible patients was calculated for Phase I (48-144). Clinical trial registry number is NCT01430351. Treatment planned: Patients accrued sequentially to ddTMZ with 1, 2, or 3 drugs. Arm 1 (ddTMZ alone) will be enrolled in Phase II only. Patients were first accrued to 1-drug Arms 2-4. Once MTDs were determined, accrual started to 2-drug Arms 5-7. Once completed, accrual to Arm 8 will start. Arms 2-4 were started at a predetermined target dose, and deescalated if excessive toxicity. Treatment in Arms 5-8 will be escalated for each drug to reach MTDs of Arms 2-4. Major eligibility criteria: Adults (≥ 18) with supratentorial GBM, KPS ≥60, adequate bone marrow and organ function. Post chemoradiation MRI ≤14 days before enrollment on stable/decreasing steroids and no progression; registration ≤5 weeks of chemoradiation. Patients on MFQ: no EIAED, EKG without prolonged QTc or arrhythmia. Pregnancy not allowed; adequate contraception required. Informed consent in keeping with IRB policies. Current enrollment: To date, 49 patients started treatment and 18 are still active. Enrollment to Arms 2-4 and 6 is completed and MTDs determined. Accrual is ongoing in Arms 5 and 7, and pending in Arm 8. Clinical trial information: NCT01430351.