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
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
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.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose Limiting Toxicities (DLT) and Maximum Tolerated Dose (MTD) of CEP 18770
Within the first 21-day cycle
Cristiana Sessa, MD, PhD
Oncology Institute of Southern Switzerland - Ospedale S. Giovanni Bellinzona CH
Italy: National Institute of Health