Related papers: Joint TITE-CRM for Dual Agent Dose Finding Studies
Traditional phase I dose finding cancer clinical trial designs aim to determine the maximum tolerated dose (MTD) of the investigational cytotoxic agent based on a single toxicity outcome, assuming a monotone dose-response relationship.…
In phase I dose escalation studies for dual-agent combinations, at least one drug often has an established monotherapy dose. Consequently, substantial prior clinical safety data often exist for one or more monotherapies, allowing the study…
Phase I dose-finding trials in oncology seek to find the maximum tolerated dose (MTD) of a drug under a specific schedule. Evaluating drug-schedules aims at improving treatment safety while maintaining efficacy. However, while we can…
The conventional more-is-better dose selection paradigm, which targets the maximum tolerated dose (MTD), is not suitable for the development of targeted therapies and immunotherapies as the efficacy of these novel therapies may not increase…
Oncology dose-finding trials are shifting from identifying the maximum tolerated dose (MTD) to determining the optimal biological dose (OBD), driven by the need for efficient methods that consider both toxicity and efficacy. This is…
An accurately identified maximum tolerated dose (MTD) serves as the cornerstone of successful subsequent phases in oncology drug development. Bayesian logistic regression model (BLRM) is a popular and versatile model-based dose-finding…
Early phase, personalized dose-finding trials for combination therapies seek to identify patient-specific optimal biological dose (OBD) combinations, which are defined as safe dose combinations which maximize therapeutic benefit for a…
We consider a modified Ci3+3 (MCi3+3) design for dual-agent dose-finding trials in which both agents are tested on multiple doses. This usually happens when the agents are novel therapies. The MCi3+3 design offers a two-stage or three-stage…
The Project Optimus initiative by the FDA's Oncology Center of Excellence is widely viewed as a groundbreaking effort to change the $\textit{status quo}$ of conventional dose-finding strategies in oncology. Unlike in other therapeutic areas…
Phase I early-phase clinical studies aim at investigating the safety and the underlying dose-toxicity relationship of a drug or combination. While little may still be known about the compound's properties, it is crucial to consider…
Combination of several anti-cancer treatments has typically been presumed to have enhanced drug activity. Motivated by a real clinical trial, this paper considers phase I-II dose finding designs for dual-agent combinations, where one main…
Background: Phase I trials desire to identify the maximum tolerated dose (MTD) early and proceed quickly to an expansion cohort or phase II trial for efficacy. We propose an early completion method based on multiple dosages to accelerate…
We propose a rule-based statistical design for combination dose-finding trials with two agents. The Ci3+3 design is an extension of the i3+3 design with simple decision rules comparing the observed toxicity rates and equivalence intervals…
The US Food and Drug Administration launched Project Optimus with the aim of shifting the paradigm of dose-finding and selection towards identifying the optimal biological dose that offers the best balance between benefit and risk, rather…
In Oncology, trials evaluating drug combinations are becoming more common. While combination therapies bring the potential for greater efficacy, they also create unique challenges for ensuring drug safety. In Phase-I dose escalation trials…
Chemotherapy is one of the primary modalities of cancer treatment. Chemotherapy drug administration is a complex problem that often requires expensive clinical trials to evaluate potential regimens. One way to alleviate this burden and…
Drug combination trials are increasingly common nowadays in clinical research. However, very few methods have been developed to consider toxicity attributions in the dose escalation process. We are motivated by a trial in which the…
The US Food and Drug Administration (FDA) launched Project Optimus and issued guidance to reform dose-finding and selection trials, shifting the paradigm from identifying the maximum tolerable dose (MTD) to determining the optimal…
The use of drug combinations in clinical trials is increasingly common during the last years since a more favorable therapeutic response may be obtained by combining drugs. In phase I clinical trials, most of the existing methodology…
We propose an adaptive design for early phase drug combination cancer trials with the goal of estimating the maximum tolerated dose (MTD). A nonparametric Bayesian model, using beta priors truncated to the set of partially ordered dose…