CDDO to Treat Solid Tumors and Lymphomas

Completed · Phase 1

Conditions studied: Solid Tumors, Lymphoma

In brief

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.

Key facts

Study ID

NCT00322140

Run by

National Cancer Institute (NCI)

People needed

7

Starts

2006-05-01

Expected to finish

2008-01-14

Last updated by the study team

2017-07-02

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Patients receiving any other investigational agents.
• Patients with known brain metastases are excluded from this clinical trial, with the exception of patients whose brain metastatic disease status has remained stable for at least 6 months after treatment of the brain metastases without steroids or anti-seizure medications. These patients may be enrolled at the discretion of the principal investigator.
• History of allergic reactions attributed to other synthetic triperinoids or compounds of similar chemical or biologic composition to CDDO, such as derivative compounds 1-[2-cyano-3-,12- dioxooleana -1,9-dien-28-oyl] imidazole (CDDO-Im), and C-28 methyl ester of 2-cyano-3,12-dioxoolen-1,9-dien-28-oic acid (CDDO-Me).
• Patients with clinically significant illnesses which could compromise participation in the study, including, but not limited to: Active or uncontrolled infection, immune deficiencies or confirmed diagnosis of HIV infection, Hepatitis B, Hepatitis C, or uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past six months, uncontrolled cardiac arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements.

Where it is running

• National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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