CDDO to Treat Solid Tumors and Lymphomas
- Conditions
- Solid TumorsLymphoma
- Registration Number
- NCT00322140
- Lead Sponsor
- National Cancer Institute (NCI)
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 7
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To determine the dose limiting toxicities, toxicity profile, and maximum tolerated dose of CDDO when administered in adult patients with solid tumors and lymphomas.
- Secondary Outcome Measures
Name Time Method To obtain preliminary evidence of anti-tumor activity of CDDO in this population.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
🇺🇸Bethesda, Maryland, United States