Study of Safety and Tolerability of Intravenous CRS-100 in Adults With Carcinoma and Liver Metastases - Full Text View

Sponsored by:	Anza Therapeutics, Inc.
Information provided by:	Anza Therapeutics, Inc.
ClinicalTrials.gov Identifier:	NCT00327652

Purpose

This clinical trial evaluated the safety and tolerability of CRS-100, an investigational agent containing a live-attenuated strain of Listeria monocytogenes (Lm). CRS-100 is attenuated by genetic modification to limit cell to cell spread and invasion of liver cells. These attenuations result in decreased virulence of CRS-100 in mice but retain the ability of the investigational agent to stimulate immunity in test animals and generate anti-tumor activity in mice. The primary objective of this study was to determine the maximum tolerated dose (MTD) and to explore the safety profile of a single intravenous dose of CRS-100 in consenting volunteers. Immunological response to CRS-100 and tumor status of study participants were also measured. Participation in this first clinical trial with CRS-100 was restricted to adults with carcinoma refractory to standard treatment (or for whom no standard treatment is available) and who additionally had liver metastases.

Condition	Intervention	Phase
Neoplasm Metastasis Liver Neoplasms Carcinoma	Drug: CRS-100	Phase I

MedlinePlus related topics: Cancer Liver Cancer

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment
Official Title:	Phase 1 Dose-Escalation Study of Safety and Tolerability of Intravenous CRS-100 in Adults With Carcinoma and Liver Metastases

Further study details as provided by Anza Therapeutics, Inc.:

Primary Outcome Measures:

Dose-limiting toxicities (DLTs) for 7 days after dosing [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]

Enrollment:	9
Study Start Date:	October 2006
Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Intervention Details:

Live-attenuated Listeria monocytogenes

Detailed Description:

Patients who consented to participate in the study were evaluated for eligibility according to their medical history, physical examination, blood testing, and computed tomography (CT) scan of thorax, abdomen, and pelvis. Those patients who qualified for the study received a single intravenous dose of CRS-100 on study day 1, after which they remained in the hospital for five days for safety monitoring of health status, including serial blood collections. Study participants returned for out-patient follow-up for further blood tests and additional monitoring of safety and immune response to CRS-100. At day 56, after administration of CRS-100, participants had a repeat CT scan to measure tumor size, and they were then discharged from the study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria (abbreviated):

Documented carcinoma refractory to standard treatment (or for whom no standard treatment is available). Hepatocellular carcinoma (HCC) is not allowed.
Hepatic metastases
ECOG Performance Status of 0 or 1, or Karnofsky Performance Status (KPS) of 80% to 100%.
Adequate organ function as defined by clinical hematology and chemistry assays.

Exclusion Criteria (abbreviated):

Known central nervous system metastases.
History of allergic reactions attributed to sulfa or beta-lactam antibiotics.
Cardiac conditions associated with high- or moderate-risk of endocarditis.
Intra-arterial hepatic catheter, hepatic cirrhosis, or clinically relevant ascites.
Artificial (prosthetic) joint or other artificial implant or devices that cannot easily be removed.
Known coagulation disorder or recent thromboembolic event.
Use of immunosuppressive agent, chemotherapy, or radiation therapy within 28 days prior to CRS-100; bone marrow or stem cell transplant or a major organ allograft; autoimmune disease.
Current history of gallstones or kidney stones.
Infection with HIV, human t-lymphotropic virus type 1 (HTLV-1), hepatitis c virus (HCV), or hepatitis b virus (HBV).
Pregnant or lactating

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00327652

Locations

United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21231
United States, Texas
Mary Crowley Medical Research Center
Dallas, Texas, United States, 75201

Sponsors and Collaborators

Anza Therapeutics, Inc.

More Information

Responsible Party:	Anza Therapeutics, Inc. ( David N. Cook, PhD )
Study ID Numbers:	VAC05001
Study First Received:	May 17, 2006
Last Updated:	April 22, 2008
ClinicalTrials.gov Identifier:	NCT00327652
Health Authority:	United States: Food and Drug Administration

Keywords provided by Anza Therapeutics, Inc.:

carcinoma
liver
hepatic
metastasis
Listeria

Study placed in the following topic categories:

Liver Neoplasms
Liver Diseases
Digestive System Diseases
Digestive System Neoplasms
Liver neoplasms

Neoplasm Metastasis
Gastrointestinal Neoplasms
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Neoplastic Processes
Neoplasms
Pathologic Processes
Neoplasms by Site
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on January 14, 2009