Protocol Number: 06-C-0172

Title:

A Phase 0 Pharmacokinetic, Pharmacodynamic Study of ABT-888, an Inhibitor of Poly (ADP-ribose) Polymerase (PARP), in Refractory Solid Tumors and Lymphoid Malignancies

Number:

06-C-0172

Summary:

Background:

-ABT-888 inhibits an enzyme called PARP that is involved in recognizing DNA damage and facilitating DNA repair. Inhibiting PARP is expected to enhance the effects of agents, such as chemotherapy and radiation therapy, that damage DNA.

Objectives:

-To understand how ABT-888 works in humans, how the body handles the drug, what side effects occur and the safety of the given doses.

Eligibility:

-Patients 18 years of age or older with solid tumors,chronic lymphocytic leukemia or follicular lymphoma for whom no standard therapy is available or for whom at least one line of standard therapy has not been successful. Patients with chronic lymphocytic leukemia and follicular lymphoma who have no received prior therapy are also eligible to participate.

Design:

-Successive groups of three patients receive ABT-888 in increasing dosages (10, 25, 50, 100 and 150 milligrams) as long as the preceding group does not develop unacceptable side effects. The drug is given by mouth as a single dose.

-Before starting the study, patients have a physical examination and blood tests, a CT scan and other imaging studies as needed, and some of the patients have to undergo a tumor biopsy (surgical removal of a small piece of tumor tissue).

-For the week prior to receiving the study drug on study, patients will need to undergo a series of 3 blood draws and maybe a tumor biopsy. For the day the drug is administered, patients are admitted to the hospital and take one dose of ABT-888 by mouth followed by blood draws to evaluate how their bodies are handling the drug and for other research studies. Some of the patients will also be required to undergo a tumor biopsy 3 to 6 hours after taking the study drug.

-Patients are discharged from the hospital 24 hours after taking the drug, to follow up in the outpatient clinic one week later. At this point, patients will have a history and physical examination along with blood work and will be taken off study

-The total duration of study participation is 2 weeks.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

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):

Phase I

Advanced Cancer

Exploratory IND

Recruitment Keyword(s):

Solid Tumor

Chronic Lymphocytic Leukemia

CLL

Follicular Lymphoma

Condition(s):

Refractory Solid Tumors

Lymphoid Malignancy

Investigational Drug(s):

ABT 888 (NSC 737664)

Investigational Device(s):

None

Interventions:

Drug: ABT 888 (NSC 737664)

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):

Tomoda T, Kurashige T, Moriki T, Yamamoto H, Fujimoto S, Taniguchi T. Enhanced expression of poly(ADP-ribose) synthetase gene in malignant lymphoma. Am J Hematol. 1991 Aug;37(4):223-7.

Shiobara M, Miyazaki M, Ito H, Togawa A, Nakajima N, Nomura F, Morinaga N, Noda M. Enhanced polyadenosine diphosphate-ribosylation in cirrhotic liver and carcinoma tissues in patients with hepatocellular carcinoma. J Gastroenterol Hepatol. 2001 Mar;16(3):338-44.

Fukushima M, Kuzuya K, Ota K, Ikai K. Poly(ADP-ribose) synthesis in human cervical cancer cell-diagnostic cytological usefulness. Cancer Lett. 1981 Dec;14(3):227-36.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department Clinical Research Informatics, CC.

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