Temporal patterns and factors associated with early termination in phase 1 clinical trials for solid tumors

Area of Science:

• Clinical trial management
• Oncology research
• Drug development

Background:

• Early termination (ET) in clinical trials, particularly phase 1 cancer studies, is not well understood.
• Identifying reasons for ET and temporal patterns is crucial for improving trial success rates.

Purpose of the Study:

• To identify and compare reasons for early termination (ET) in phase 1 cancer trials versus late-phase trials.
• To investigate temporal trends and factors associated with ET in phase 1 cancer trials.

Main Methods:

• Analysis of 2301 solid tumor trials (1740 phase 1, 561 phase 2-3) initiated between 2018-2023 from ClinicalTrials.gov.
• Comparison of ET reasons using Chi-squared tests.
• Time-to-event analysis and multivariable logistic regression to identify determinants of ET.

Main Results:

• Sponsor/strategic decisions were the primary reason for ET in phase 1 trials (51.1%), contrasting with poor accrual in phase 2-3 trials (35.5%).
• ET probability in phase 1 trials peaked between 10-30 months and plateaued after 60 months.
• Academic funding and trials in Europe, Asia, or Oceania were associated with lower ET risk; global trials and thoracic/gastrointestinal cancers had higher ET risk.

Conclusions:

• Phase 1 cancer trial discontinuation is mainly driven by sponsor decisions, influenced by funding, tumor type, and location.
• The identified critical window for ET in phase 1 trials suggests opportunities for intervention to enhance trial sustainability.