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A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition
Published on: September 20, 2019
Efficacy assessment in phase I clinical trials: endpoints and challenges
M A Gouda1, P A Ballesteros2, I Garrido-Laguna3
1Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA.
Abstract:
The scope of phase I clinical trials in oncology goes beyond the conventional safety evaluation-only objectives of these trials in other specialties. Rather, most first-in-human oncology clinical trials have therapeutic intent, and efficacy signals observed in phase I trials can drive a go/no-go decision of advancing a new molecule to phase II testing. The complexity of efficacy assessment in the context of a small, heterogeneous patient population and a complex study design requires a more liberal perspective compared with later trial phases when looking into efficacy endpoints. Classically, in later-phase clinical trials, these endpoints would include the objective response rate, progression-free survival, and overall survival. However, new, evolving endpoints may be worth investigating when looking into the antitumor activity signals in phase I trials. Integration of all these endpoints into trial designs can improve the assessment of therapeutic efficacy during early drug development and guide decisions related to the further advancement of novel molecules into later phases. In this review, we discuss the advantages and pitfalls of different classic efficacy endpoints when evaluated as part of phase I trials in oncology and describe how challenges in assessing the antitumor activity of new drugs can be overcome through the incorporation of novel endpoints that have thus far proven successful in clinical trials.
Insights
Phase I oncology trials assess safety and efficacy, guiding new drug development. Incorporating novel endpoints improves antitumor activity assessment in early drug development.
Area of Science:
- Oncology
- Clinical Pharmacology
- Drug Development
Background:
- Phase I oncology trials traditionally focus on safety but increasingly include therapeutic intent.
- Efficacy signals in Phase I trials significantly influence decisions for advancing new oncology drugs to Phase II.
- Assessing efficacy in small, heterogeneous Phase I populations requires flexible endpoint evaluation.
Purpose of the Study:
- To review the utility and limitations of classic efficacy endpoints in Phase I oncology trials.
- To explore the potential of novel efficacy endpoints for assessing antitumor activity in early-phase studies.
- To provide guidance on integrating diverse endpoints for improved early drug development decision-making.
Main Methods:
- Review of classic efficacy endpoints (e.g., objective response rate, progression-free survival, overall survival) in Phase I oncology trials.
- Discussion of challenges in efficacy assessment within small, heterogeneous patient cohorts.
- Exploration of emerging and novel endpoints for evaluating antitumor activity.
Main Results:
- Classic endpoints have limitations in Phase I oncology trials due to small sample sizes and study designs.
- Novel endpoints offer valuable insights into antitumor activity, complementing traditional measures.
- Integrated endpoint assessment enhances the evaluation of therapeutic efficacy in early drug development.
Conclusions:
- Phase I oncology trials require a nuanced approach to efficacy assessment beyond safety.
- Incorporating novel endpoints can overcome challenges in evaluating early antitumor responses.
- Optimized endpoint strategies in Phase I trials are crucial for effective novel oncology drug development.
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