Protocol Number: 06-C-0151

Title:

Phase I Study of CDDO in Solid Tumors and Lymphomas

Number:

06-C-0151

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.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

Metastatic

Triterpenoids

2-Cyano-3,12-Dioxooleana-1,9(11)Dien-28oic Acid

Dose-Limiting

Pharmacokinetics

Recruitment Keyword(s):

Solid Tumor

Lymphoma

Condition(s):

Solid Tumors

Lymphoma

Investigational Drug(s):

CDDO

Investigational Device(s):

None

Interventions:

Drug: CDDO

Supporting Site:

National Cancer Institute

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

Ito Y, Pandey P, Sporn MB, Datta R, Kharbanda S, Kufe D. The novel triterpenoid CDDO induces apoptosis and differentiation of human osteosarcoma cells by a caspase-8 dependent mechanism. Mol Pharmacol. 2001 May;59(5):1094-9

Lapillonne H, Konopleva M, Tsao T, Gold D, McQueen T, Sutherland RL, Madden T, Andreeff M Activation of peroxisome proliferator-activated receptor gamma by a novel synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces growth arrest and apoptosis in breast cancer cells. Cancer Res. 2003 Sep 15;63(18):5926-39

Ito Y, Pandey P, Place A, Sporn MB, Gribble GW, Honda T, Kharbanda S, Kufe D. The novel triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid induces apoptosis of human myeloid leukemia cells by a caspase-8-dependent mechanism Cell Growth Differ. 2000 May;11(5):261-7

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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