Related papers: Dose-Escalation Trial Protocols that Extend Natura…
Personalized cancer treatments based on the molecular profile of a patient's tumor are an emerging and exciting class of treatments in oncology. As genomic tumor profiling is becoming more common, targeted treatments to specific molecular…
In medical treatment and elsewhere, it has become standard to base treatment intensity (dosage) on evidence in randomized trials. Yet it has been rare to study how outcomes vary with dosage. In trials to obtain drug approval, the norm has…
With the development of novel therapies such as molecularly targeted agents and immunotherapy, the maximum tolerated dose paradigm that "more is better" does not necessarily hold anymore. In this context, doses and schedules of novel…
Treatment planning uncertainties are typically managed using margin-based or robust optimization. Margin-based methods expand the clinical target volume (CTV) to a planning target volume, generally unsuited for proton therapy. Robust…
Novel dose-finding designs, using estimation to assign the best estimated maximum- tolerated-dose (MTD) at each point in the experiment, most commonly via Bayesian techniques, have recently entered large-scale implementation in Phase I…
Personalizing combination therapies in oncology requires navigating an immense space of possible drug and dose combinations, a task that remains largely infeasible through exhaustive experimentation. Recent developments in patient-derived…
In this article, we propose a phase I-II design in two stages for the combination of molecularly targeted therapies. The design is motivated by a published case study that combines a MEK and a PIK3CA inhibitors; a setting in which higher…
Phase I dose-escalation trials must be guided by a safety model in order to avoid exposing patients to unacceptably high risk of toxicities. Traditionally, these trials are based on one type of schedule. In more recent practice, however,…
To promote precision medicine, individualized treatment regimes (ITRs) are crucial for optimizing the expected clinical outcome based on patient-specific characteristics. However, existing ITR research has primarily focused on scenarios…
Purpose: We propose a general framework for quantifying predictive uncertainties of dose-related quantities and leveraging this information in a dose mimicking problem in the context of automated radiation therapy treatment planning.…
In traditional dose-finding studies, dose-limiting toxicity (DLT) is determined within a fixed time observation window where DLT is often defined as a binary outcome. In the setting of oncology dose-finding trials, often patients in…
The primary goal of dose allocation in phase I trials is to minimize patient exposure to subtherapeutic or excessively toxic doses, while accurately recommending a phase II dose that is as close as possible to the maximum tolerated dose…
Although optimal control theory has been used for the theoretical study of anti-cancerous drugs scheduling optimization, with the aim of reducing the primary tumor volume, the effect on metastases is often ignored. Here, we use a previously…
Dose optimization in oncology clinical trials has shifted from seeking the maximum tolerated dose to identifying the Optimal Biological Dose (OBD) that balances therapeutic benefits and risks across multiple clinical attributes. Existing…
The use of `backfilling', assigning additional patients to doses deemed safe, in phase I dose-escalation studies has been used in practice to collect additional information on the safety profile, pharmacokinetics and activity of a drug.…
Conventionally, a first-in-human phase I trial in healthy volunteers aims to confirm the safety of a drug in humans. In such situations, volunteers should not suffer from any safety issues and simple algorithm-based dose-escalation schemes…
Clinical trials with time-to-event endpoints, such as overall survival (OS) or progression-free survival (PFS), are fundamental for evaluating new treatments, particularly in immuno-oncology. However, modern therapies, such as…
Nowadays, more and more clinical trials choose combinational agents as the intervention to achieve better therapeutic responses. However, dose-finding for combinational agents is much more complicated than single agent as the full order of…
Combination drug therapies hold significant promise for enhancing treatment efficacy, particularly in fields such as oncology, immunotherapy, and infectious diseases. However, designing clinical trials for these regimens poses unique…
In oncology dose-finding trials, due to staggered enrollment, it might be desirable to make dose-assignment decisions in real-time in the presence of pending toxicity outcomes, for example, when the dose-limiting toxicity is late-onset.…