Phase I Oncology Drug Developmen

Description:

This book provides a detailed review of how oncology drug development has changed over the past decade, and serves as a comprehensive guide for the practicalities in setting up phase I trials. The book covers strategies to accelerate the development of novel antitumor compounds from the laboratory to clinical trials and beyond through the use of innovative mechanism-of-action pharmacodynamic biomarkers and pharmacokinetic studies. The reader will learn about all aspects of modern phase I trial designs, including the incorporation of precision medicine strategies, and approaches for rational patient allocation to novel anticancer therapies. Circulating biomarkers to assess mechanisms of response and resistance are changing the way we are assessing patient selection and are also covered in this book. The development of the different classes of antitumor agents are discussed, including chemotherapy, molecularly targeted agents, immunotherapies and also radiotherapy. The authors also discuss the lessons that the oncology field has learnt from the development of hematology-oncology drugs and how such strategies can be carried over into therapies for solid tumors. There is a dedicated chapter that covers the specialized statistical approaches necessary for phase I trial designs, including novel Bayesian strategies for dose escalation. This volume is designed to help clinicians better understand phase I clinical trials, but would also be of use to translational researchers (MDs and PhDs), and drug developers from academia and industry interested in cancer drug development. It could also be of use to phase I trial study coordinators, oncology nurses and advanced practice providers. Other health professionals interested in the treatment of cancer will also find this book of great value.

Table of Contents:

1. The Development of a Drug: A Pharmaceutical Drug Development Perspective

2. Paradigms in Cancer Drug Development: A Universe with Many Galaxies

3. Preclinical Studies to Enable First in Human Clinical Trials

4. Practicalities of Setting Up a Phase I Clinical Trial Unit Within an Academic Center

5. Novel Trial Designs for Early Phase Clinical Trials

6. Examining Performance of Phase I Designs: 3+3 Versus Bayesian Optimal Interval (BOIN)

7. Considerations for the Attribution and Management of Toxicities in Phase I Clinical Trials

8. Strategies for Incorporating Pharmacokinetic Studies into Oncology Phase I Trials

9. Development of Pharmacodynamic Biomarkers for Phase I Trials

10. Efficacy Considerations in Phase I Trials

11. Considerations for the Development of Novel Chemotherapies and Antibody Drug Conjugates in Phase I Trials

12. Development of Molecularly Targeted Agents in Early Phase Clinical Trials

13. Incorporating Precision Medicine into Phase I Clinical Trials

14. Incorporating Circulating Biomarkers into Clinical Trials

15. Development of Immunotherapeutic Strategies for Early Phase Clinical Trials

16. Radiotherapy Considerations and Strategic Approaches in Phase I Trials

17. The Paradigm of Early Phase Studies in Hematological Malignancies

18. Pharmacokinetic Considerations for Organ Dysfunction Clinical Trials in Early Drug Development