9 results on '"Rebecca Herbertson"'
Search Results
2. Abstract CT256: Modi-1, anti-citrullinated neoepitope vaccine alone and combined with checkpoint inhibitors in patients with head and neck, breast, renal and ovarian carcinoma: protocol for the ModiFY phase I/II basket clinical Ttial
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Lindy G. Durrant, Fayaz Masters, Samantha Paston, Robert Miller, David J. Pinato, Rebecca Herbertson, Anne Armstrong, Stefan Symeonides, and Christian Ottensmeier
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Cancer Research ,Oncology - Abstract
Stressful conditions in the tumor microenvironment induce autophagy in cancer cells as a mechanism to promote their survival. High levels of calcium within autophagosomes activates peptidylarginine deaminase enzymes which convert arginine residues within polypeptides to citrulline and alters proteolytic cleavage. In the presence of inflammation, the MHC-II pathway presents these new citrullinated peptides to CD4 T cells. Modi-1 vaccine comprising three citrullinated, adjuvanted peptides induces and expands a population of activated CD4 T cells. On reaching the tumor site the CD4 T cells release proinflammatory cytokines including, INFγ, which upregulates MHC class II and the same, but endogenous, modified peptides are presented on the tumor cell surface. This likely causes a positive feed-forward loop with killing of tumor cells. The objective of this study is to evaluate the safety, tolerability, cellular immune and tumor response to 2 citrullinated vimentin and one citrullinated enolase peptide each conjugated to the toll-like receptor 1/2 adjuvant Amplivant® ModiFY is an open-label, prospective, multicohort, multicenter, phase I/II basket trial. Eligible patients have unresectable disease in one of the following tumor types: Squamous Cell Carcinoma of the Head and Neck (SCCHN), Triple Negative Breast Cancer, Renal Cell Carcinoma and High Grade Serous Ovarian Carcinoma. Depending on the status of the disease and eligibility for standard of care (SOC) checkpoint inhibitor (CPI) monotherapy, patients will be treated either with Modi-1 alone or Modi-1 +SOC CPI. A randomized neoadjuvant sub-study in patients with SCCHN scheduled to have tumor resection surgery is included in the protocol. These patients are randomized 1:1 to receive either Modi-1 alone or Modi-1+ pembrolizumab. The primary endpoints are the adverse event rate as measured by CTCAE v5.0 in the initial dose escalation cohorts and the strength of the cellular immune response IFNγ enzyme-linked immune absorbent spot (ELISpot) assay in the dose expansion cohorts. Secondary endpoints (RECIST 1.1 and iRECIST), are objective response rate duration of response, progression-free survival, and overall survival. In the SCCHN neoadjuvant cohort, tumor infiltrating lymphocytes in resected tumor tissue will be profiled using scRNAseq and immunohistochemistry. The study is an adaptive trial, comprising 3+3 dose escalation cohorts followed by a Simon 2-stage design in the dose expansion cohorts. The Modi-1 only dose expansion cohort will recruit 16 patients of each of the target tumor types, whilst the Modi-1+CPI will recruit a total of 21 patients. A total of 21/138 patients have been treated to date. ClinicalTrials.gov NCT05329532 Citation Format: Lindy G. Durrant, Fayaz Masters, Samantha Paston, Robert Miller, David J. Pinato, Rebecca Herbertson, Anne Armstrong, Stefan Symeonides, Christian Ottensmeier. Modi-1, anti-citrullinated neoepitope vaccine alone and combined with checkpoint inhibitors in patients with head and neck, breast, renal and ovarian carcinoma: protocol for the ModiFY phase I/II basket clinical Ttial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT256.
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- 2023
3. 498 Edmond: a feasibility study of elemental diet as an alternative to parenteral nutrition for ovarian cancer patients with inoperable malignant bowel obstruction
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Agnieszka Michael, Simon S. Skene, Kate Bennett-Eastely, Rebecca Herbertson, and Lindsey Allan
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medicine.medical_specialty ,Elemental diet ,business.industry ,medicine.disease ,Bowel obstruction ,Parenteral nutrition ,Quality of life ,Tolerability ,Internal medicine ,medicine ,Clinical endpoint ,Vomiting ,medicine.symptom ,Ovarian cancer ,business - Abstract
Introduction/Background Inoperable bowel obstruction (IBO) occurs in up to 50% of patients diagnosed with ovarian cancer. Nutrition support for patients with IBO is challenging. Parenteral feeding (PN) is the recommended route for patients with a prognosis of > 2 months, however there is little evidence that it improves quality of life and the cost of it is very high. If PN is not available patients are frequently discharged home from hospital with sips of clear fluids only. Management of inoperable bowel obstruction remains a major challenge and clear guidelines are needed. Elemental diet (ED) is a liquid diet that contains proteins in the form of amino acids, fats in the form of medium chain triglycerides, vitamins and trace minerals. ED is almost completely absorbed in the upper small intestine. Methodology The primary objective of the study was to establish if ED can be used as an alternative to home PN in patients with IBO. The secondary aim was to examine the impact of ED on quality of life. The primary endpoints of the study were acceptability and tolerability of ED with respect to taste, and incidence of vomiting and pain. The secondary endpoints included the number of patients alive at the end of the study, quality of life, nutritional intake, and the number of women who can tolerate ED and subsequently be treated with palliative chemotherapy (as per standard of care). Results 29 women with IBO caused by metastatic ovarian cancer were recruited into the EDMONd study. Of those 8 could not complete the trial due to disease progression, and 2 had missing data that was deemed irretrievable, leaving 19 patients who contributed data to the primary endpoint analysis. The mean age of the patients who continued the trial was 68 (SD 12.5). Preliminary analysis shows that 68.4% of patients met the primary endpoint and tolerated ED; the ED did not worsen the vomiting or pain as measured by Memorial Symptoms Assessment Scale. At baseline 72% of patients experienced vomiting and this number reduced to 28% by the end of week1 of the study and to 23.5% by the end of week 2. 96% of patients reported pain at baseline and this proportion reduced to 72% and 76% by the end of week 1 and 2 respectively. Conclusion ED is well tolerated by patients with IBO and can provide an acceptable feeding option for this group of patients. Disclosures The study was funded by Target Ovarian Cancer charity. The author received educational grants from BMS, GSK, IPSEN, NOVARTIS, PFIZER CLOVIS, TESARO, ESAI; Advisory boards: CLOVIS, ESAI, IPSEN, ROCHE, TESARO
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- 2020
4. EDMOND: A FEASIBILITY STUDY OF ELEMENTAL DIET AS AN ALTERNATIVE TO PARENTERAL NUTRITION FOR OVARIAN CANCER PATIENTS WITH INOPERABLE MALIGNANT BOWEL OBSTRUCTION
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Simon Skene, Kate Bennett Eastley, Rebecca Herbertson, Lindsey Allan, and Agnieszka Michael
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- 2020
5. A phase I clinical trial with monoclonal antibody ch806 targeting transitional state and mutant epidermal growth factor receptors
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Scott, Andrew M., Lee, Fook-Thean, Tebbutt, Niall, Rebecca, Herbertson, Gill, Sanjeev S., Liu, Zhanqi, Skrinos, Effie, Murone, Carmel, Saunder, Timothy H., Chappell, Bridget, Papenfuss, Anthony T., Poon, Aurora M.T., Hopkins, Wendie, Smyth, Fiona E., MacGregor, Duncan, Cher, Lawrence M., Jungbluth, Achim A., Brechbiel, Martin W., Murphy, Roger, Burgess, Antony W., Hoffman, Eric W., Johns, Terrance G., and Old, Lloyd J.
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Monoclonal antibodies -- Research ,Cell surface antigens -- Research ,Tumor antigens -- Research ,Science and technology - Abstract
An array of cell-surface antigens expressed by human cancers have been identified as targets for antibody-based therapies. The great majority of these antibodies do not have specificity for cancer but recognize antigens expressed on a range of normal cell types (differentiation antigens). Over the past two decades, our group has analyzed thousands of mouse monoclonal antibodies for cancer specificity and identified a battery of antibodies with limited representation on normal human cells. The most tumor-specific of these antibodies is 806, an antibody that detects a unique epitope on the epidermal growth factor receptor (EGFR) that is exposed only on overexpressed, mutant, or ligand-activated forms of the receptor in cancer. In vitro immunohistochemical specificity analysis shows little or no detectable 806 reactivity with normal tissues, even those with high levels of wild-type (wt)EGFR expression. Preclinical studies have demonstrated that 806 specifically targets a subset of EGFR expressed on tumor cells, and has significant anti-tumor effects on human tumor xenografts, primarily through abrogation of signaling pathways. The present clinical study was designed to examine the in vivo specificity of a chimeric form of mAb 806 (ch806) in a tumor targeting/biodistribution/ pharmacokinetic analysis in patients with diverse tumor types. ch806 showed excellent targeting of tumor sites in all patients, no evidence of normal tissue uptake, and no significant toxicity. These in vitro and in vivo characteristics of ch806 distinguish it from all other antibodies targeting EGFR. tumor | immunotherapy | anti-erbB1 | biodistribution
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- 2007
6. Efficacy of Reduced-Intensity Chemotherapy With Oxaliplatin and Capecitabine on Quality of Life and Cancer Control Among Older and Frail Patients With Advanced Gastroesophageal Cancer
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Pei Loo Ow, Angel Garcia, Lesley Samuel, Rajarshi Roy, Adam McGeoch, D. Fyfe, W Saku, Simon Aird Grumett, Jonathan Nicoll, Jo Dent, Tom Samuel Waddell, Jo Webster, Christine Allmark, Tania Tillett, Colin Askill, Justin S. Waters, C. Handforth, Erica Beaumont, Vallipuram Vigneswaran, Sharon Ruddock, Nick Wadd, Syed Zubair, Kinnari Patel, Vanessa Potter, Daniel Propper, Olwyn Williams, Marc Jones, Kamalnayan Guptal, Peter Hall, Gareth Griffiths, Joseph Mano, Juan W. Valle, Sheela Rao, David A Cairns, Go Trial Investigators, Eszter Katona, Nick Maisey, Chris Twelves, Daniel Swinson, Nicholas Reed, Heike I. Grabsch, Joanne Askey, Jonathan Wadsley, Tom Roques, Sue Cheeseman, Stephen Falk, Louise Medley, Arshad Jamil, Emma Cattell, Victori Kunene, Matthew R. Sydes, Charles Candish, Claire Hobbs, Rebecca Herbertson, Jo Parkinson, Nicholas S. Reed, Louise Brook, Zuzana Stokes, Mohammed Khan, Ann Crossley, Elin Jones, George Bozas, Sebastian Cummins, Anirban Chatterjee, Michael Bennet, Helen Marshall, Pavel Bezecny, David Sherriff, Matthew T. Seymour, Lauren Gorf, Galina Velikova, Jean Gall, Kamposioras Konstantinos-Velios, Sally Clive, Eleanor James, Fiona Collinson, Dunca Wilkins, Simon Lord, Julia Brown, Serena Hilman, A. Robinson, Richard Ellis, Alaaeldin Shablak, Russell D Petty, Sherif Raouf, Helen Howard, RS: GROW - R2 - Basic and Translational Cancer Biology, and Pathologie
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Cancer Research ,medicine.medical_specialty ,Randomization ,EUROPEAN-ORGANIZATION ,law.invention ,II TRIAL ,Capecitabine ,ESOPHAGOGASTRIC JUNCTION ,03 medical and health sciences ,REGRESSION-MODELS ,0302 clinical medicine ,Randomized controlled trial ,Quality of life ,law ,Internal medicine ,medicine ,030212 general & internal medicine ,ELDERLY-PATIENTS ,ADVANCED GASTRIC-CANCER ,business.industry ,Hazard ratio ,ADENOCARCINOMA ,Combination chemotherapy ,Chemotherapy regimen ,FLUOROURACIL ,Oxaliplatin ,METASTATIC COLORECTAL-CANCER ,Oncology ,030220 oncology & carcinogenesis ,1ST-LINE THERAPY ,business ,medicine.drug - Abstract
Importance: Older and/or frail patients are underrepresented in landmark cancer trials. Tailored research is needed to address this evidence gap. Objective: The GO2 randomized clinical trial sought to optimize chemotherapy dosing in older and/or frail patients with advanced gastroesophageal cancer, and explored baseline geriatric assessment (GA) as a tool for treatment decision-making. Design, Setting, and Participants: This multicenter, noninferiority, open-label randomized trial took place at oncology clinics in the United Kingdom with nurse-led geriatric health assessment. Patients were recruited for whom full-dose combination chemotherapy was considered unsuitable because of advanced age and/or frailty. Interventions: There were 2 randomizations that were performed: CHEMO-INTENSITY compared oxaliplatin/capecitabine at Level A (oxaliplatin 130 mg/m 2on day 1, capecitabine 625 mg/m 2twice daily on days 1-21, on a 21-day cycle), Level B (doses 0.8 times A), or Level C (doses 0.6 times A). Alternatively, if the patient and clinician agreed the indication for chemotherapy was uncertain, the patient could instead enter CHEMO-BSC, comparing Level C vs best supportive care. Main Outcomes and Measures: First, broad noninferiority of the lower doses vs reference (Level A) was assessed using a permissive boundary of 34 days reduction in progression-free survival (PFS) (hazard ratio, HR = 1.34), selected as acceptable by a forum of patients and clinicians. Then, the patient experience was compared using Overall Treatment Utility (OTU), which combines efficacy, toxic effects, quality of life, and patient value/acceptability. For CHEMO-BSC, the main outcome measure was overall survival. Results: A total of 514 patients entered CHEMO-INTENSITY, of whom 385 (75%) were men and 299 (58%) were severely frail, with median age 76 years. Noninferior PFS was confirmed for Levels B vs A (HR = 1.09 [95% CI, 0.89-1.32]) and C vs A (HR = 1.10 [95% CI, 0.90-1.33]). Level C produced less toxic effects and better OTU than A or B. No subgroup benefited from higher doses: Level C produced better OTU even in younger or less frail patients. A total of 45 patients entered the CHEMO-BSC randomization: overall survival was nonsignificantly longer with chemotherapy: median 6.1 vs 3.0 months (HR = 0.69 [95% CI, 0.32-1.48], P =.34). In multivariate analysis in 522 patients with all variables available, baseline frailty, quality of life, and neutrophil to lymphocyte ratio were independently associated with OTU, and can be combined in a model to estimate the probability of different outcomes. Conclusions and Relevance: This phase 3 randomized clinical trial found that reduced-intensity chemotherapy provided a better patient experience without significantly compromising cancer control and should be considered for older and/or frail patients. Baseline geriatric assessment can help predict the utility of chemotherapy but did not identify a group benefiting from higher-dose treatment. Trial Registration: isrctn.org Identifier: ISRCTN44687907.
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- 2021
7. OCTOPUS: A randomised, multi-centre phase II umbrella trial of weekly paclitaxel+/- novel agents in platinum-resistant ovarian cancer—Vistusertib (AZD2014)
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Cecilia Orbegoso, Clare Green, Cheryl Wilson, Aishah Hanif, Susana Banerjee, Udai Banerji, Iain A. McNeish, Andrew R Clamp, Hani Gabra, Rebecca Herbertson, Liz-Anne Lewsley, and James Paul
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Oncology ,Cancer Research ,medicine.medical_specialty ,biology ,business.industry ,VISTUSERTIB ,Weekly paclitaxel ,biology.organism_classification ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,Novel agents ,030220 oncology & carcinogenesis ,Internal medicine ,Octopus (genus) ,medicine ,030212 general & internal medicine ,Multi centre ,business ,Ovarian cancer ,Platinum resistant - Abstract
TPS5609 Background: There is an urgent need to improve outcomes for patients with platinum-resistant and refractory ovarian cancer (PROC). OCTOPUS is an umbrella phase II framework for testing whether the addition of novel targeted agents to weekly paclitaxel (wPxl) improves efficacy in PROC. The first agent to be evaluated is the dual mTORC1/mTORC2 inhibitor, vistusertib (AZD2014), as preclinical studies support targeting the PI3kinase/Akt/mTOR pathway in PROC and the combination of vistusertib and wPxl has shown promising preliminary activity in high grade serous ovarian cancer (HGS) patients in a phase I trial (Banerji et al poster discussion ESMO 2016). This is the first randomised trial of wPxl and a dual mTORC1/2 inhibitor in ovarian cancer. Methods: OCTOPUS is an investigator-initiated, randomised, double-blind, placebo-controlled, multicentre, phase II trial. 140 patients with PROC (histologically confirmed HGS) are randomised 1:1 to receive wPxl (80mg/m2 D1, D8, D15 of 28 day cycle) plus oral vistusertib (50mg BD) or placebo (D1-3, D8-10, D15-17). The primary endpoint is progression-free survival (PFS) based on combined RECIST v1.1/GCIG CA125 criteria. The study is designed to detect a 50% improvement in median PFS from 3.7 months on placebo to 5.55 months on the experimental arm with 90% power, at the 20% 1-sided level of statistical significance (or equivalently with 80% power at the 10% level of statistical significance) using a 3-outcome design. Secondary endpoints include response (based on RECIST 1.1 and GCIG CA125 criteria), overall survival, toxicity and quality of life. Patients whom received prior wPxl for PROC are not eligible. A mandatory pre-treatment biopsy (if technically feasible), archival tissue, and serial blood samples will be collected for translational research studies. 49 patients have been recruited. The study is part of the NIHR CRN Cancer/Astrazeneca Alliance, sponsored by NHS Greater Glasgow and Clyde/University of Glasgow and endorsed by Cancer Research UK (CRUKE/14/052). Clinical trial information: ISRCTN16426935.
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- 2017
8. Bilateral peripheral T-cell lymphoma of the fallopian tubes
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Ahmet Dogan, Rebecca Herbertson, Peter Davis, Judith Gaffan, and Alison Jones
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medicine.medical_specialty ,Pathology ,animal structures ,medicine.medical_treatment ,Fallopian Tube Lymphoma ,Uterus ,CHOP ,Lymphoma, T-Cell ,hemic and lymphatic diseases ,Laparotomy ,medicine ,T-cell lymphoma ,Fallopian Tube Neoplasms ,Humans ,Gynecology ,business.industry ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,Peripheral T-cell lymphoma ,Lymphoma ,medicine.anatomical_structure ,Oncology ,Female ,business ,Fallopian tube - Abstract
Background. Lymphoma of the female genital tract is rare, and usually involves the ovaries or the uterus. Most cases of fallopian tube lymphoma reflect disease arising in the ovaries. All previously reported cases of primary lymphoma of the fallopian tube were of B cell lineage. Case. A 51-year-old woman presented with systemic upset and a pelvic mass. At laparotomy, both fallopian tubes were inflamed and histological examination revealed peripheral T-cell lymphoma. At staging, she had IIB(E) disease, and she was treated with six cycles of CHOP-M chemotherapy. Conclusion. Our case is unusual in that this is the first described case of peripheral T-cell lymphoma arising in the fallopian tubes and is moreover unusual because of the involvement of both fallopian tubes without involvement of other gynaecological organs. The clinical course was favourable with complete remission maintained for more than 5 years.
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- 2004
9. Epidermal growth factor receptor (EGF-R) inhibitors for metastatic colorectal cancer
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Rebecca Herbertson, Christos Karapetis, Tim Price, Niall Tebbutt, and Nick Pavlakis
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