Related Experiment Video
Updated: Jun 20, 2025
Non-invasive Assessment of the Efficacy of New Therapeutics for Intestinal Pathologies Using Serial Endoscopic Imaging of Live Mice
Published on: March 10, 2015
Bayesian sequential monitoring strategies for trials of digestive cancer therapeutics
Guillaume Mulier1,2, Ruitao Lin3, Thomas Aparicio4,5
1ECSTRRA team UMR 1153, INSERM, Saint-Louis hospital, 1 avenue Claude Vellefaux, Paris, 75010, France. guillaume.mulier@u-paris.fr.
Background:
New therapeutics in oncology have presented challenges to existing paradigms and trial designs in all phases of drug development. As a motivating example, we considered an ongoing phase II trial planned to evaluate the combination of a MET inhibitor and an anti-PD-L1 immunotherapy to treat advanced oesogastric carcinoma. The objective of the paper was to exemplify the planning of an adaptive phase II trial with novel anti-cancer agents, including prolonged observation windows and joint sequential evaluation of efficacy and toxicity.
Methods:
We considered various candidate designs and computed decision rules assuming correlations between efficacy and toxicity. Simulations were conducted to evaluate the operating characteristics of all designs.
Results:
Design approaches allowing continuous accrual, such as the time-to-event Bayesian Optimal Phase II design (TOP), showed good operating characteristics while ensuring a reduced trial duration. All designs were sensitive to the specification of the correlation between efficacy and toxicity during planning, but TOP can take that correlation into account more easily.
Conclusions:
While specifying design working hypotheses requires caution, Bayesian approaches such as the TOP design had desirable operating characteristics and allowed incorporating concomittant information, such as toxicity data from concomitant observations in another relevant patient population (e.g., defined by mutational status).
Insights
Adaptive phase II trial designs, like the time-to-event Bayesian Optimal Phase II (TOP) design, offer efficient evaluation of novel oncology therapeutics, including combinations of MET inhibitors and anti-PD-L1 immunotherapies.
Area of Science:
- Oncology
- Clinical Trial Design
- Biostatistics
Background:
- Novel oncology therapeutics challenge traditional trial designs.
- Focus on a phase II trial for advanced oesogastric carcinoma combining a MET inhibitor and anti-PD-L1 immunotherapy.
Purpose of the Study:
- To exemplify adaptive phase II trial planning for new anti-cancer agents.
- To incorporate prolonged observation and sequential efficacy/toxicity evaluation.
Main Methods:
- Evaluated candidate adaptive designs and decision rules.
- Simulated operating characteristics, considering efficacy-toxicity correlations.
- Assessed continuous accrual designs like the time-to-event Bayesian Optimal Phase II (TOP) design.
Main Results:
- Continuous accrual designs, such as TOP, demonstrated favorable operating characteristics and reduced trial duration.
- All designs were sensitive to efficacy-toxicity correlation assumptions.
- TOP design effectively incorporated correlation information.
Conclusions:
- Bayesian approaches like TOP offer desirable operating characteristics for adaptive trials.
- These methods facilitate the integration of concomitant toxicity data from related patient populations.
- Careful specification of design hypotheses is crucial for robust trial planning.
Related Concept Videos
01:21Cancer Survival Analysis
01:24Kaplan-Meier Approach