Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 38 for “"dose escalation"”.
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A Phase I Dose-Escalation Study of The Braf Inhibitor Vemurafenib In Combination With The Mtor Inhibitor Everolimus In Subjects With Advanced Cancer
… objective is to find the maximum tolerated dose (MTD) and the toxicity of the combination of vemurafenib and everolimus following a standard 3 + 3 design. The most common diagnosis was melanoma in 5 out of 10 patients (50%). Male patients in 7 out of 10 patients (70%). The average age was …
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Novel methods for early phase clinical trials
… objective. The initial focus of the thesis is on dose-escalation. In the single-agent setting, subgroups of the population, between which the reaction to treatment may differ, are accounted for in dose-escalation. This is achieved using a Bayesian model-based approach to dose-escalation with spike …
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Bayesian Phase I Dose Finding In Cancer Trials
<p>This dissertation explores phase I dose-finding designs in cancer trials from three perspectives: the alternative Bayesian dose-escalation rules, a design based on a time-to-dose-limiting toxicity (DLT) model, and a design based on a discrete-time multi-state (DTMS) model.</p> <p>We list …
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Intensity modulated radiotherapy for skull base meningioma
… is an effective treatment for meningioma, with doses of 50-54Gy in conventional fractionation schedules resulting in long-term local control rates of 80-90%. However, local recurrence is unacceptably high in aggressive histological subtypes (WHO G2 and G3), and these patients have a poor outcome …
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Improving The Accuracy of Radiation Pneumonitis Dose Response Models
… been reported to be 15%. Studies have shown that dose escalation to the tumor can lead to better local control and subsequently better overall survival. However, dose to lung tumor is limited by normal tissue toxicity. The most prevalent thoracic toxicity is radiation pneumonitis. In order to …
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Evaluation of the Pharmacokinetic-Pharmacodynamic relationship, Metabolism and Plasma Protein Binding of the novel antitumor agent, 2-Methoxyestradiol (2ME2), following oral administration in patients with solid tumors.
… solid tumors and determine maximum tolerated dose (MTD). The following hypotheses were tested: 1) 2ME2 will be well tolerated in clinic when given orally and will have quantifiable effects on the ex vivo markers of angiogenesis and apoptosis; 2) 2ME2 will exhibit linear pharmacokinetics; 3) …
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A Nomogram for Valproic Acid and the Effect of Missed Doses
… are divided on dosing recommendations when a dose is delayed or missed. For a neuropsychiatric agent like valproic acid (VPA), rational dosing recommendations are of particular importance. VPA is subject to therapeutic monitoring using total concentrations. Due to non-linear binding of VPA to …
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PHARMACOLOGICAL MODULATION OF THE ADAPTIVE IMMUNE SYSTEM IN ISCHAEMIC HEART DISEASE
… Several small clinical studies have used low dose interleukin-2 (ld-IL-2) to increase Treg cells in patients with various autoimmune but not cardiovascular diseases. Therefore, a phase 1/2a, randomised, placebo-controlled, double-blind, dose-escalation, two-part clinical trial was performed to …
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Dual-Criterion Dose Finding Designs for Phase I Clinical Trials
… tolerability of novel therapeutics. Conventional dose escalation methods identify the maximum tolerated dose (MTD) based on dose-limiting toxicity (DLT). However, as cancer therapies have evolved from chemotherapy to targeted therapies, these traditional methods have become problematic. Many …
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Investigation of focused Very High Energy Electrons (VHEEs) as a new radiotherapy method
… is faced with the challenge of delivering doses which exceed standard clinical fractions to target radioresistant tumours. However, any dose escalation in the tumour is limited by radiation tolerance of healthy tissues,including skin, which is among the most sensitive tissue. An improved …
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Comparison of two saline loading protocols for preventing nephrotoxicosis associated with high-dose cisplatin
… dogs. Nephrotoxicosis was initially considered dose limiting. The use of saline loading and hypertonic saline administration protocols allowed dose escalation, reduced nephrotoxicosis, and increased remission rates in the treatment previously poorly responsive malignant tumors in human beings. A …
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Novel Phase I/II Designs for Cytotoxic and Cytostatic Agents, and Combination Treatments
… develops innovative Bayesian adaptive dose-finding designs for early-phase oncology trials, aiming to improve the identification of optimal biological doses (OBDs) by jointly modeling safety and efficacy. Unlike conventional Phase I designs that rely solely on binary toxicity outcomes …
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Investigation of Quatitative Image Features From Pretreatment Ct and Fdg-Pet Scans In Stage Iii Nsclc Patients Undergoing Defintive Radiation Therapy
… survival differences based on radiation dose.</p> <p>QIFs were found to provide additional prognostic information beyond that found from CPFs. Initial evidence suggests that the examined FDG-PET based QIFs may have utility across cohorts and could potentially determine which patients may …
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Optimization and toxocologic effects of cancer immuno-electrogene therapy using a tumor-targeted interleukin-12 gene construct
… in C3H/HeJ mice by identifying an initial safe dose for human dose escalation schemes, toxicity target organs, markers of toxicity, and toxicity reversibility. Dystrophic cardiac calcification in older, 5 ìg ttIL-12-treated mice was the only serious toxicity. Based on these results and the lack …
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Feasibility of selective multiple boosting in the planning of intracranial radiation therapy
… provides unprecedented means to sculpt radiation dose in three-dimensions, pledging potential to improve local disease control via conformal dose escalation as well as better normal tissue sparing via conformal avoidance. In this thesis, the feasibility and practicality of delivering high doses to …
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PARP inhibition in combination with radiation therapy for the treatment of feline oral squamous cell carcinoma
… quantified and displayed with digital imaging. A dose escalation study in healthy cats was performed assessing Olaparib safety and pharmacokinetics, and these preclinical findings guided a comparative clinical trial combining Olaparib and stereotactic radiotherapy (SRT) in 20 cats with OSCC. …
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Investigation of the role of antagonism of the Interleukin-7 Receptor in the treatment of Multiple Sclerosis in Humans and In Vitro differences between genetically stratified subjects based on Interleukin-7 Receptor Genotype
… which was well tolerated as part of a dose escalation sub-study of the CAMTHY trial. The main CAMTHY trial investigated if palifermin could cause increased thymic lymphopoiesis, offsetting the IL-7 driven homeostatic proliferation of lymphocytes and secondary autoimmunity associated …
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Modulation of the tumor microenvironment by the CXCR4 antagonist AMD3100 in pancreatic and colorectal adenocarcinoma
… and pharmacokinetic results from the CAMPLEX dose escalation phase are presented. A dose-rate of AMD3100 80ug/kg/hr was safe, reasonably well tolerated, and achieved relevant plasma concentrations at steady state. However, pharmacodynamic makers of CXCR4 inhibition, including peripheral white …
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Novel Bayesian Adaptive Clinical Trial Designs In Early Phases
… clinical trials is to establish the recommended dose of new drugs for phase II trials. For the cytotoxic drugs, the goal is to find maximum tolerated dose (MTD). The guiding principle for dose escalation in phase I trials is to avoid exposing too many patients to subtherapeutic doses while …
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Stromal-epithelial dynamics in response to fractionated radiotherapy
… continued debate as to what might be the proper dose per fraction as well as the total dose of radiation that needs to be prescribed to prevent disease recurrence. Countries outside the US have adopted increased dose fractionation (i.e., hypofractionation) schemes for early stage breast cancer as …
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