Irinotecan Plus Cyclosporine and Phenobarbital in Treating Patients With Solid Tumors or Lymphoma
|Drug/Agent Toxicity by Tissue/Organ Lymphoma Neutropenia Small Intestine Cancer Unspecified Adult Solid Tumor, Protocol Specific||Drug: cyclosporine Drug: irinotecan hydrochloride Drug: phenobarbital||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A PHASE I STUDY OF IRINOTECAN (CPT-11) WITH PHARMACOKINETIC MODULATION BY CYCLOSPORINE A AND PHENOBARBITAL|
|Study Start Date:||June 1996|
|Primary Completion Date:||April 2002 (Final data collection date for primary outcome measure)|
Experimental: Arm I
See detailed description.
|Drug: cyclosporine Drug: irinotecan hydrochloride Drug: phenobarbital|
I. Determine the maximum tolerated dose of irinotecan (CPT-11) when infused weekly with cyclosporine (CYSP) in patients with solid tumors or lymphoma refractory to standard therapy.
II. Determine whether CYSP modulates the pharmacokinetics and pharmacodynamics of CPT-11 and its active metabolite, SN-38.
III. Determine whether phenobarbital modulates the pharmacokinetics and pharmacodynamics of CPT-11 and SN-38.
OUTLINE: This is a dose escalation study of irinotecan. Patients are stratified according to gender.
Part I: Patients receive cyclosporine IV over 6 hours and irinotecan IV over 90 minutes weekly for 4 weeks. Courses repeat every 6 weeks in the absence of unacceptable toxicity or disease progression. Cohorts of 3-12 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least one third of patients experience dose limiting toxicity (DLT).
Part IIA: If the DLT is diarrhea in part I, then part IIA is opened. Patients receive oral phenobarbital, cyclosporine as in part I, and irinotecan at the MTD from part I. Dose escalation occurs as in part I to determine a new MTD. If the DLT continues to be diarrhea, the study is closed. Part IIB: If the DLT is neutropenia in part I, then part IIB is opened. Patients receive cyclosporine as in part I and escalating doses of irinotecan to determine a new MTD.
Part III: If the DLT is neutropenia in part IIA or any DLT in part IIB, patients receive phenobarbital, cyclosporine, and irinotecan at the MTD determined as in part IIA or part IIB. Dose escalation continues until a new MTD is determined.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002759
|United States, Illinois|
|University of Chicago Cancer Research Center|
|Chicago, Illinois, United States, 60637-1470|
|Study Chair:||Mark J. Ratain, MD||University of Chicago|