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 15 of 15 for “"maximum tolerated dose (MTD)"”.
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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
… of vemurafenib and everolimus will be well tolerated. The primary 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%). …
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Modified 3+3 Design for MTD Re-estimation
… clinical trial design is one of the most popular dose-finding designs used in phase I oncology trials to identify the maximum tolerated dose (MTD) for new treatment regimens. While this design is widely used due to its simplicity , it has some notable limitations, including a maximum of six …
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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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Therapeutic Effects and Targeted Delivery of Eupenifeldin in Castration-Resistant Prostate Cancer
… Eupenifeldin inhibits cell proliferation in a dose-dependent manner and induces apoptotic cell death through caspase-3/7 activation, suggesting that apoptotic pathways mediate its anticancer effects. Mechanistic studies revealed that Eupenifeldin caused a broad reduction in kinase …
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Bayesian Adaptive Clinical Trial Design
… and dysfunctional. Specifically, the focus of dose-finding trials has shifted from finding the maximum tolerated dose (MTD) to the optimal biological dose (OBD), defined as the dose that optimizes the risk–benefit tradeoff. How to accurately identify the OBD and its dosing schedule is of great …
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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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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.
… 2ME2 in patients with 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 …
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Drug delivery of paclitaxel for an intraperitoneal chemotherapy
… the toxicity of both formulations was similar (maximum tolerated dose (MTD) of 0.24 mg/ml for both). Bioavailability, however, was significantly increased for Pac/RAME-beta-CD (i.e. 40-fold increase for the area under the curve). Preliminary results from the TGD study allowed to establish the …
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Pharmacological characterisation of selected pyrrolobenzodiazepines as anti-cancer agents. Pharmacokinetic and pharmacodynamic characterisation of the pyrrolobenzodiazepine dimer SJG-136 and the monomers D709119, MMY-SJG and SJG-303
… in mice via both the i.p. and i.v. route (dosed at the maximum tolerated dose (MTD)) showed that SJG-136 reaches concentrations in plasma well in excess of the in vitro IC50 values for 1 h exposure, and was detected in tumour and brain samples also above the in vitro IC50 values. …
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Targeting head and neck squamous cell carcinoma through NQO1-mediated cytotoxicity
… in attempts to find a derivative with a greater maximum tolerated dose (MTD) or more favorable pharmacokinetics. Future studies involving NQO1-independent ROS generation, methemoglobin formations and tumor penetrations are currently being investigated to differentiate DNQ derivatives and identify …
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Bayesian Semi-Mechanistic Dose-Finding Designs For Phase I Oncology Trials
… In oncology, despite the great advances in novel dose-finding designs, the high failure rates of clinical cancer drug development from phase I to III trials call for further improvements on novel designs, in addition to the need to promote and adopt novel designs in practice. Because anticancer …
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An Innovative Phase I Trial Design Allowing For The Identification of Multiple Potential Maximum to lerated Doses With Combination Therapy of Targeted Agents
… to different agents, and 3) higher achievable dose intensity by exploiting non-overlapping toxicities to the host. Even if the toxicity profile of each agent of a given combination is known, the toxicity profile of the agents used in combination must be established. Thus, caution is required …
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Immunotoxin Monotherapy and Combinatorial Therapy With Immune Checkpoint Inhibitors for Malignant Brain Tumors
… in normal Sprague-Dawley (SD) rats. The maximum tolerated dose (MTD) of D2C7-IT was determined to be between a total dose of 0.10 and 0.35 μg, and the no-observed-adverse-effect level (NOAEL) of D2C7-IT was a total dose of 0.05 μg in SD rats. Both the MTD and NOAEL were utilized as …
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Bayesian Designs For Early Phase Clinical Trials With Novel Target Agents
… designs have been proposed to find the maximum tolerated dose (MTD) in phase I clinical trials, but their differences and relative pros and cons are not clear to many practitioners. We review three model-based designs, including the continual reassessment method (CRM), dose escalation …
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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 …