Phase I Study of the Proteosome Inhibitor CEP 18770 in Patients With Solid Tumours or Non-Hodgkin's Lymphomas
This Phase 1 escalating-dose study is designed to assess, the safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel proteasome inhibitor CEP 18770, given intravenously as single agent, in patients with advanced, incurable solid tumours or NHL, and to identify the recommended dose of CEP 18770 to be used in Phase 2 studies.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-Label, Dose-escalation, Phase I Study to Determine the Maximum Tolerated Dose, Recommended Dose, Pharmacokinetics, and Pharmacodynamics of the Proteosome Inhibitor CEP 18770 Given Intravenously as Single Agent in Patients With Advanced Solid Tumours or Non-Hodgkin's Lymphomas|
- Dose Limiting Toxicities (DLT) and Maximum Tolerated Dose (MTD) of CEP 18770 [ Time Frame: Within the first 21-day cycle ] [ Designated as safety issue: Yes ]
- Pharmacokinetics of CEP-18770 following single and multiple dose administration. [ Time Frame: Within the first 21-day cycle ] [ Designated as safety issue: No ]
- Profile and time course of inhibition and recovery of proteasome activity [ Time Frame: Within the first 21-day cycle ] [ Designated as safety issue: No ]
- Antineoplastic activity evaluated with internationally accepted response criteria [ Time Frame: throughout the study period ] [ Designated as safety issue: No ]
|Study Start Date:||November 2007|
|Study Completion Date:||March 2010|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
This is an open-label, multicenter, dose-escalating study to determine the MTD and dose limiting toxicities (DLTs) of CEP 18770, a novel proteasome inhibitor. The study will also characterize the pharmacokinetics and the pharmacokinetic/pharmacodynamic relationship of CEP 18770, and assess the safety and tolerability of CEP-18770 treatment as well as any effect on tumour response whenever possible.
Patients will be treated intravenously with CEP 18770 on days 1, 4, 8, and 11 of a 21-day cycle period. Additional cycles may be administered, up to 6, as long as patients are maintaining their performance status and appear to be receiving clinical benefit from the study.
Safety data will be collected for all patients in order to determine the toxicity and reversibility of toxicity of CEP 18770. Formal assessments will be performed throughout the study including at baseline, prior to each dose of study medication every week, and 30 days following the last dose of study drug. Patients with drug-related toxicities will continue to be reviewed until resolution or stabilization of the toxicity. Pharmacokinetic and pharmacodynamic parameters will also be assessed in each cohort of patients during cycle 1. Where applicable, tumour measurements will be documented and any observed anti-tumour activity will be evaluated.
The study will follow a conventional MTD design with patients recruited in cohorts of 3 patients, with criteria to expand to 6 patients. Enrolment for each cohort will begin when the required number of patients in the prior cohort have completed one 21-day cycle of study drug treatment at the current dose level without experiencing a DLT. Once the MTD has been determined, additional 10 patients will be treated at the MTD to further explore the toxicity of this dose, and its suitability for Phase II studies.
|Europen Institute of Oncology|
|Milano, Italy, 20141|
|IOSI - Oncology Institute of Southern Switzerland - Ospedale S. Giovanni|
|Bellinzona, Switzerland, 6500|
|Kantonsspital St. Gallen|
|St. Gallen, Switzerland, 9007|
|Principal Investigator:||Cristiana Sessa, MD, PhD||Oncology Institute of Southern Switzerland - Ospedale S. Giovanni Bellinzona CH|