Study of XL228 Administered Intravenously to Subjects With Advanced Malignancies - Full Text View

Sponsor:	Exelixis
Information provided by:	Exelixis
ClinicalTrials.gov Identifier:	NCT00526838

Purpose

The purpose of this study is to assess the safety and tolerability of the multi-targeted protein kinase inhibitor XL228 (active against IGF1R, Src, FGFR, and BCR-Abl) administered as a once- or twice-weekly 1-hour intravenous infusion in subjects with advanced malignancies.

Condition	Intervention	Phase
Cancer Lymphoma	Drug: XL228	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 1 Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of XL228 Administered Intravenously to Subjects With Advanced Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma

U.S. FDA Resources

Further study details as provided by Exelixis:

Primary Outcome Measures:

To assess the safety and tolerability of XL228 administered as a once-weekly or twice-weekly 1-hour intravenous (IV) infusion in subjects with advanced malignancies. [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: Yes ]
To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of XL228 administered as a once- or twice-weekly 1-hour IV infusion in subjects with advanced malignancies. [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To evaluate plasma pharmacokinetics of XL228 administered as a once- or twice-weekly 1-hour IV infusion in subjects with advanced malignancies. [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: No ]
To evaluate preliminary safety and efficacy of XL228 when administered at the once-weekly MTD [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	100
Study Start Date:	September 2007
Estimated Study Completion Date:	June 2011
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 once-weekly dosing	Drug: XL228 1-hour IV infusion
Experimental: 2 twice-weekly dosing	Drug: XL228 1-hour IV infusion

Eligibility

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

Criteria

Inclusion Criteria:

The subject has a histologically confirmed solid tumor that is metastatic or unresectable, lymphoma, or multiple myeloma, and for which standard curative or palliative measures do not exist or are no longer effective, and there are no known therapies to prolong survival. Subjects treated at the MTD (once-weekly) must have a diagnosis of metastice colorectal carcinoma, relapsed or refractory multiple myeloma, non-small-cell lung cancer (NSCLC), or small cell lung cancer (SCLC). Certain other eligibility requirements must also be met.
The subject has disease that is assessable by tumor marker, clinical laboratory, physical, or radiologic means.
The subject is ≥18 years old.
The subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
The subject has adequate organ and marrow function.
The subject is capable of understanding the informed consent document and has signed the informed consent document.
Sexually active subjects (male and female) must use medically acceptable methods of contraception during the course of the study.
Female subjects of childbearing potential must have a negative serum pregnancy test at screening.

Exclusion Criteria:

The subject has received anticancer treatment (eg, chemotherapy, radiotherapy, cytokines, investigational agent, or hormones) within 14 days before the first dose of study drug.
The subject has received radiation to >25% of his or her bone marrow within 30 days of treatment with XL228.
The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade ≤1 from adverse events (AEs) due to investigational or other agents administered more than 14 days prior to study enrollment.
The subject has a primary brain tumor. Subjects with brain metastases are considered eligible if the subject has not received radiation therapy for brain metastasis within 2 weeks of enrollment and has been on a stable dose of steroids for 2 or more weeks.
The subject has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, diabetes, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
The subject has a psychiatric illness or social situation that would limit compliance with study requirements.
The subject is pregnant or breastfeeding.
The subject is known to be positive for the human immunodeficiency virus (HIV).
The subject has a known allergy or hypersensitivity to components of the XL228 formulation.
The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00526838

Locations

United States, California
UCLA Jonsson Comprehensive Cancer Center
Los Angeles, California, United States, 90095
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States, 48109
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710

Sponsors and Collaborators

Exelixis

More Information

No publications provided

Responsible Party:	Natalie Sacks, MD/Vice President, Clinical Research, Exelixis, Inc.
ClinicalTrials.gov Identifier:	NCT00526838 History of Changes
Other Study ID Numbers:	XL228-002
Study First Received:	September 6, 2007
Last Updated:	April 4, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Exelixis:

Solid Tumor
Multiple Myeloma

Additional relevant MeSH terms:

Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders

Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on February 09, 2012