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SPIRIT: A seamless phase I/II randomized design for immunotherapy trials
Author(s) -
Guo Beibei,
Li Daniel,
Yuan Ying
Publication year - 2018
Publication title -
pharmaceutical statistics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.421
H-Index - 38
eISSN - 1539-1612
pISSN - 1539-1604
DOI - 10.1002/pst.1869
Subject(s) - immunotherapy , clinical endpoint , medicine , clinical trial , immune system , cancer immunotherapy , oncology , survival analysis , progression free survival , randomized controlled trial , overall survival , immunology
Immunotherapy—treatments that enlist the immune system to battle tumors—has received widespread attention in cancer research. Due to its unique features and mechanisms for treating cancer, immunotherapy requires novel clinical trial designs. We propose a Bayesian seamless phase I/II randomized design for immunotherapy trials (SPIRIT) to find the optimal biological dose (OBD) defined in terms of the restricted mean survival time. We jointly model progression‐free survival and the immune response. Progression‐free survival is used as the primary endpoint to determine the OBD, and the immune response is used as an ancillary endpoint to quickly screen out futile doses. Toxicity is monitored throughout the trial. The design consists of two seamlessly connected stages. The first stage identifies a set of safe doses. The second stage adaptively randomizes patients to the safe doses identified and uses their progression‐free survival and immune response to find the OBD. The simulation study shows that the SPIRIT has desirable operating characteristics and outperforms the conventional design.