Phase I Study of CDDO in Solid Tumors and Lymphomas
- CDDO is a novel synthetic triterpenoid which is a potent multifunctional molecule. It
induces apoptosis in vitro in malignant cells through both intrinsic and extrinsic
pathways, and it controls cellular differentiation, apoptosis, and growth inhibition by
serving as a ligand for the transcription factor peroxisome proliferator activator
receptor-gamma (PPAR gamma).
- Based on in vitro activity, it holds considerable promise as a novel anti-tumor agent
against a wide range of malignancies by concurrently targeting multiple pathways
leading to oncogenesis.
- In vivo data demonstrates that the drug is well tolerated in dogs, and has anti-tumor
effects, dependent upon dose schedule.
- To determine the dose limiting toxicities, toxicity profile, and maximum tolerated dose
of CDDO when administered in adult patients with solid tumors and lymphomas.
- To characterize the pharmacokinetics of CDDO.
- To obtain preliminary evidence of anti-tumor activity of CDDO in this population.
- To evaluate the in vivo molecular and biological effects of CDDO by assessing changes
in biomarkers of apoptosis and cell cycle arrest.
- Patients with advance, histological-confirmed malignancies refractory to standard
therapy or for which no standard therapy exist.
- Patients should have adequate liver, renal and bone marrow function.
- Accordingly with the accelerated titration design 4B, dose levels will initially be
increased at 100% increments, and one new patient per dose level will be treated per
- The accelerated phase ends when one patient experiences DLT during any course of
treatment or when two different patients experience grade 2 toxicity during first
course of treatment.
- When the first instance of grade 2 toxicity is observed two additional patients must
have been treated at that dose, or a higher dose, (during any course) without
experiencing moderate or worse toxicity, in order that the accelerated phase continue.
- When the accelerated phase ends, dose-escalation will revert to a more conservative
modified Fibonacci scheme with 40% dose-step increments, with at least 3 patients
treated per dose level.
Primary Purpose: Treatment
To determine the dose limiting toxicities, toxicity profile, and maximum tolerated dose of CDDO when administered in adult patients with solid tumors and lymphomas.
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|