Spots Global Cancer Trial Database for CDDO to Treat Solid Tumors and Lymphomas

Study Description

Brief Summary: Background: * 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. Objectives: Primary: * 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. Secondary: * 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. Eligibility: * 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. Study Design: * 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 4-week course. * 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.

Detailed Description: Background: * 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. Objectives: Primary: * 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. Secondary: * 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. Eligibility: * 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. Study Design: * 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 4-week course. * 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.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

Useful links and downloads for this trial