Dose-Escalation Scheme (Renal Dysfunction) Please state route and schedule of Study Agent administration, and enter exact doses for each dose level and group in the table below. (For example, XXX is given intravenously as a “Agent 1-hour infusion on days 1, 3, and 5 of a 21-day cycle.) is given on of a cycle. [CTEP IND [route/duration] [day/days] [#]-day Group A Group B Group C Group D Group E Normal Mild renal Moderate Severe renal Kidney function dysfunction renal dysfunction dialysis Dose (units) * dysfunction Level (units) * (units) * (units) * (units) * Level -1 TBD** *** 1 TBD** *** TBD** *** Level 2 3 TBD** *** Level 4 TBD** *** * are stated as exact dose in clinically utilized units (e.g., mg/m2, mcg/kg, etc.) rather than as a percentage. ** To be determined on the safety data available for Normal and Moderate at the time that this group potentially would be activated for enrollment Section 6.2 for the E dosing scheme. See Section 6.2 for definitions of dysfunction groups. The cohort of patients will be treated at dose level 1. Dose level is only to be –1 used if dose reduction is necessary. The following modifications to the usual dose escalation scheme allow for the “3&3” dosing of new patients in the event that not all patients treated at a current dose level are yet evaluable for toxicity. Dose Escalation Rules Dose escalation will proceed within each renal dysfunction group according to the scheme outlined in Section 6.6. DLT is defined above (Section 6.4). Only DLTs that during the first cycle of treatment will be used to guide dose escalation. Patients are considered evaluable for toxicity when they have received the planned dose or duration of therapy and have either 1) experienced DLT or 2) been followed for one full without DLT. Dose Escalation Definitions
Dose-Escalation Scheme (Renal Dysfunction) Please state route and schedule of Study Agent administration, and enter exact doses for each dose level and group in the table below. (For example, “Agent XXX is given intravenously as a 1-hour infusion on days 1, 3, and 5 of a 21-day cycle.) [CTEP IND is given [route/duration] on [day/days] of a [#]-day cycle. Group A Group B Group C Group D Group E Dose Level Normal function (units) * Mild renal dysfunction (units) * Moderate renal dysfunction (units) * Severe renal dysfunction (units) * Kidney dialysis (units) * Level -1 TBD** *** 1 TBD** *** Level 2 TBD** *** 3 TBD** *** Level 4 TBD** *** * are stated as exact dose in clinically utilized units (e.g., mg/m2, mcg/kg, etc.) rather than as a percentage. ** To be determined on the safety data available for Normal and Moderate at the time that this group potentially would be activated for enrollment Section 6.2 for the E dosing scheme. See Section 6.2 for definitions of dysfunction groups. The cohort of patients will be treated at dose level 1. Dose level –1 is only to be used if dose reduction is necessary. The following modifications to the usual “3&3” dose escalation scheme allow for the dosing of new patients in the event that not all patients treated at a current dose level are yet evaluable for toxicity. Dose Escalation Rules Dose escalation will proceed within each renal dysfunction group according to the scheme outlined in Section 6.6. DLT is defined above (Section 6.4). Only DLTs that during the first cycle of treatment will be used to guide dose escalation. Patients are considered evaluable for toxicity when they have received the planned dose or duration of therapy and have either 1) experienced DLT or 2) been followed for one full without DLT. Dose Escalation Definitions
CTEP_Organ_Dysfunction_Protocol_Template.docx