Treatment schema
Tumor, diarrhea
ADVERSE EVENTS, DISEASE, TUMOR
Initially, protocol therapy included VIT (vincristine 1.5 mg/mTrial design: (A) Schema for the original trial VIT cycle without metformin prior to addition of metformin in Cycle 2 (or 3) depending on hematologic tolerance. “Heme Recovery” signifies ANC > 1000 and Platelets >100,000 on Day 21 of a cycle. (B) Post‐amendment schema showing the addition of metformin in Cycle 1. (C) Trial profile accounting for all patients screened for enrollment.Temozolomide was required to be given at least one hour prior to the other agents. For Day 1, vincristine was given at least one hour after temozolomide and at least one hour prior to irinotecan. Irinotecan‐induced diarrhea prophylaxis was required with cefpodoxime or cefixime beginning one to two days prior and continuing one to two days post‐irinotecan. Alternative antibiotic prophylaxis was allowed per discretion of the study team. Supportive care for irinotecan early‐ and late‐onset diarrhea was required including use of loperamide, atropine, and octreotide based on symptom timing and intensity.Tumor resections were allowed on study after the DLT period if deemed clinically indicated by the treating physician. Radiotherapy was not permitted. Subjects were removed from protocol therapy for clinical or radiographic progressive disease, drug‐related adverse events that did not improve or recurred despite dose modifications, refusal of protocol therapy, non‐compliance that in the investigator's opinion precluded ongoing participation, completion of 12 cycles, or if the treating physician determined it was not in the best interest of the patient to continue protocol therapy.