Oncology phase I trial design and conduct: time for a change - MDICT Guidelines 2022

Area of Science:

• Oncology
• Clinical Trial Design
• Pharmacology

Background:

• The Food and Drug Administration's Project Optimus highlights the need for optimized oncology drug dosing.
• Current methods of defining single recommended phase II doses may not yield the most effective or best-tolerated treatments.
• The Methodology for the Development of Innovative Cancer Therapies (MDICT) Taskforce convened to address these limitations.

Purpose of the Study:

• To develop a practical guide for optimizing dosage in early-phase oncology clinical trials.
• To recommend strategies for selecting optimal doses that balance efficacy and tolerability.
• To improve the selection of anticancer drug dosages in clinical practice.

Main Methods:

• Review and discussion by the MDICT Taskforce.
• Emphasis on robust non-clinical data to inform trial design.
• Incorporation of expert teams including statisticians and pharmacologists.
• Development of flexible and adaptive trial protocols with clear endpoints.
• Consultation with health authorities.

Main Results:

• Recommendations for improved oncology trial design, including dose selection.
• Encouragement of strategies like randomization and intrapatient dose escalation.
• Discouragement of serial tumor sampling without strong rationale.
• Emphasis on considering longitudinal toxicity and diverse patient populations.
• Advocacy for defining recommended dose ranges rather than single doses.

Conclusions:

• Adoption of MDICT recommendations will enhance dosage selection in early-phase oncology trials.
• Improved dosage selection is expected to lead to better patient outcomes in cancer therapy.
• The guidelines aim to ensure new anticancer treatments are both effective and well-tolerated.