Study design
tumor, DLTs, toxicity, toxicities, Chase Cancer
FOX, TUMOR, DISEASE PROGRESSION
The study was conducted in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki and was approved by the Fox Chase Cancer Center (FCCC) Institutional Review Board. This was a single-center, investigator-initiated phase I trial. The study was pre-registered at clinicaltrials.gov and first posted November 25, 2015 (Patients in each cohort were assessed for dose-limiting toxicities (DLTs) as specified in the protocol (provided in the supplementary material) over the first six weeks of the combination phase, not including the one-week IFN-γ induction since that time period would not have reflected DLTs from the combination. If two or more DLTs occurred in any cohort, that dose of IFN-γ would be deemed intolerable and the prior completed dose would be considered the maximum tolerated dose (MTD). Patients that were not evaluable for DLT because they went off trial for disease progression or withdraw of consent without receiving 75% of IFN-γ doses were replaced, but were included in overall safety analysis. Based on a complete assessment of toxicity, as well as correlative factors, the study team had authority to denote the MTD as the recommended phase two dose (RP2D), or if warranted for safety and/or scientific reasons, a lower dose could also be chosen as the RP2D.Patients were seen every two weeks once they entered the combination phase, then every three weeks during the single agent phase. RECIST version 1.1 was used to assess objective tumor response, with assessments performed after the combination phase and then every 9 weeksAll patients provided written informed consent and were not compensated for study participation. The first patient was enrolled 12/29/2015 and the last patients was enrolled 2/12/2018. A steering committee consisting of select study investigators and staff met after each dose cohort to review safety data and decide whether to proceed to the next dose, and the study conduct was also reviewed regularly by an independent FCCC data safety monitoring board. The study was conducted at and sponsored by Fox Chase Cancer Center and all data was evaluated independently. Funding for study conduct and IFN-γ administration was provided by Horizon Pharma, LLC. The original design included plans for expansion cohorts to assess preliminary efficacy as measured by response rate in specific cancers of interest; however, the funding organization elected to halt further trial conduct after the Phase I portion. The original plan can be found in the full protocol in the supplement, but no changes to analysis or design of the phase I portion were made.