Related Experiment Video

Updated: Mar 7, 2026

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

8.0K

Dose-finding designs for trials of molecularly targeted agents and immunotherapies

Cody Chiuzan1, Jonathan Shtaynberger1, Gulam A Manji2

  • 1a Department of Biostatistics, Mailman School of Public Health , Columbia University , New York , New York , USA.

Journal of Biopharmaceutical Statistics
|February 7, 2017
PubMed

Insights

Novel dose-finding designs for early phase oncology trials are underutilized. Despite a tripling in adoption, rule-based designs remain dominant, even for molecularly targeted agents and immunotherapies.

Area of Science:

  • Oncology
  • Clinical Trial Design
  • Pharmacology

Background:

  • Early phase oncology trials are increasingly using molecularly targeted agents (MTAs) and immunotherapies.
  • These novel therapies possess distinct toxicity profiles compared to traditional cytotoxic agents.
  • Existing trial designs may not optimally accommodate the characteristics of new therapeutic agents.

Purpose of the Study:

  • To assess the adoption rate of novel dose-finding designs in phase 1 oncology trials.
  • To evaluate the utilization of advanced trial designs for molecularly targeted agents and immunotherapies.
  • To compare the use of novel designs across different therapeutic modalities.

Main Methods:

  • A Web of Science search identified phase 1 oncology trials published between 2008 and 2014.
  • Trials were categorized by dose-finding design (rule-based vs. model-based/novel) and drug type (MTA, immunotherapy, chemotherapy, radiotherapy).
  • Statistical analysis was performed to determine adoption percentages and trends.

Main Results:

  • Out of 1,712 trials, 92.9% used rule-based designs, while only 5.4% employed model-based or novel designs.
  • Model-based designs were slightly more common in MTA/immunotherapy trials (5.8%) compared to chemotherapy (3.9%) or radiotherapy (8.3%).
  • The percentage of trials using novel designs tripled from 2007 to 2014, but overall adoption remained low.

Conclusions:

  • The adoption of innovative dose-finding methodologies in early phase oncology trials remains limited.
  • Rule-based designs continue to dominate, despite the rise of targeted therapies and immunotherapies.
  • Further research and implementation efforts are needed to increase the use of advanced trial designs.
Keywords:
Dose-finding methodsimmunotherapymaximum tolerated doseoptimal dosephase 1 designstargeted therapy

More Related Videos

Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction09:44

Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction

Published on: January 29, 2019

10.7K
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo12:42

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo

Published on: January 7, 2019

10.3K

Related Concept Videos

Dosage Regimens: Designs and Approaches01:28

Dosage Regimens: Designs and Approaches

Designing a dosage regimen, which refers to the manner of drug administration, is a complex process involving the selection of drug dose, route, and frequency. This process is underpinned by pharmacokinetic parameters derived from tests and population averages. These parameters are then tailored to patient-specific variables such as diagnosis, demographics, and allergy status. Once therapy commences, therapeutic response monitoring is critical and achieved through clinical and physical...
406
Clinical Trials: Overview01:11

Clinical Trials: Overview

Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
5.2K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.0K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
60
Drug Discovery: Overview01:26

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
12.5K
Dose Size and Dosing Frequency: Determination Methods01:21

Dose Size and Dosing Frequency: Determination Methods

Determining the optimal dose size and dosing frequency in pharmacotherapy is crucial for achieving therapeutic effectiveness while minimizing adverse effects. This article explores the methodologies employed in determining these parameters, focusing on their significance and interplay to tailor dosing regimens.Dose Size: Dose size refers to the amount of a drug administered in a single dose. It is determined based on the drug's pharmacodynamics and pharmacokinetics properties and...
456